dementia_AB_final_v6.1.json

{
  "name": "Dementia",
  "remarks": [
    "right now this is just Alzheimer's but there are other dementias that could be adapted into this model"
  ],
  "states": {
    "Initial": {
      "type": "Initial",
      "distributed_transition": [
        { "distribution": 0.98, "transition": "Assign_APOE_Genotype" },
        { "distribution": 0.02, "transition": "PreEarlyOnsetAlzheimers" }
      ],
      "remarks": [
        "Alzheimer's has been shown to be significantly based on genetics, and there are specific genes to point to for early-onset:",
        "https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-genetics-fact-sheet",
        "Since Synthea does not currently model at the level of individual genes",
        "we'll use a simple probability to differentiate the population into who will and won't get alzheimers.",
        "The 40% chance does seem high, but the key factor here is the delay in when it appears.",
        "38% of people over age 85 have alzheimer's. ( http://www.alzheimers.net/resources/alzheimers-statistics/ )"
      ]
    },
    
    "Assign_APOE_Genotype": {
     "type": "Simple",
     "conditional_transition": [
       {"transition": "APOE White", "condition": {"condition_type": "Race", "race": "White"}},
       {"transition": "APOE Black", "condition": {"condition_type": "Race", "race": "Black"}},
       {"transition": "APOE Asian", "condition": {"condition_type": "Race", "race": "Asian"}}
     ]
    },
    "APOE White": {
     "type": "Simple",
     "distributed_transition": [
       {"transition": "Set_e2e2", "distribution": 0.0064},
       {"transition": "Set_e2e3", "distribution": 0.1248},
       {"transition": "Set_e2e4", "distribution": 0.0224},
       {"transition": "Set_e3e3", "distribution": 0.6084},
       {"transition": "Set_e3e4", "distribution": 0.2184},
       {"transition": "Set_e4e4", "distribution": 0.0196}
     ],
     "remarks": [
      "APOE genotype probabilities vary by ancestry (Zhang et al., 2022; Meliani et al., 2021; Saddiki et al., 2020; Blackman et al., 2022).",
      "White/European ancestry: ε2 = 0.08, ε3 = 0.78, ε4 = 0.14 ",
      "Black/Sub-Saharan ancestry: ε2 = 0.10, ε3 = 0.70, ε4 = 0.20",
      "Asian/East Asian ancestry: ε2 = 0.07, ε3 = 0.82, ε4 = 0.11",
      "Transition probabilities calculated using Hardy-Weinberg formula."
      ]
    },
    
   "APOE Black": {
    "type": "Simple",
    "distributed_transition": [
    {"transition": "Set_e2e2", "distribution": 0.0100},
    {"transition": "Set_e2e3", "distribution": 0.1400},
    {"transition": "Set_e2e4", "distribution": 0.0400},
    {"transition": "Set_e3e3", "distribution": 0.4900},
    {"transition": "Set_e3e4", "distribution": 0.2800},
    {"transition": "Set_e4e4", "distribution": 0.0400}
   ]
  },


  "APOE Asian": {
   "type": "Simple",
   "distributed_transition": [
     {"transition": "Set_e2e2", "distribution": 0.0049},
     {"transition": "Set_e2e3", "distribution": 0.1148},
     {"transition": "Set_e2e4", "distribution": 0.0154},
     {"transition": "Set_e3e3", "distribution": 0.6724},
     {"transition": "Set_e3e4", "distribution": 0.1804},
     {"transition": "Set_e4e4", "distribution": 0.0121}
   ]
  },

  "Set_e2e2": {
    "type": "SetAttribute", 
    "attribute": "apoe_genotype", 
    "value": "e2/e2", 
    "direct_transition": "Diagnosis_e2e2"
   },
   
   "Diagnosis_e2e2": {
      "type": "Observation",
      "category": "survey",
      "exact": { "quantity": 1 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72234-8", "display": "e2/e2" }
      ],
      "direct_transition": "APOE_Risk_E2E2"
    },
 
  "Set_e2e3": {
    "type": "SetAttribute", 
    "attribute": "apoe_genotype", 
    "value": "e2/e3", 
    "direct_transition": "Diagnosis_e2e3"
   },
   
   "Diagnosis_e2e3": {
      "type": "Observation",
      "category": "survey",
      "exact": { "quantity": 1 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72234-8", "display": "e2/e3" }
      ],
      "direct_transition": "APOE_Risk_E2E3"
    },
 
  "Set_e2e4": {
    "type": "SetAttribute", 
    "attribute": "apoe_genotype", 
    "value": "e2/e4", 
    "direct_transition": "Diagnosis_e2e4"
  },
  
  "Diagnosis_e2e4": {
      "type": "Observation",
      "category": "survey",
      "exact": { "quantity": 1 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72234-8", "display": "e2/e4" }
      ],
      "direct_transition": "APOE_Risk_E2E4"
    },
 
  "Set_e3e3": {
    "type": "SetAttribute", 
    "attribute": "apoe_genotype", 
    "value": "e3/e3", 
    "direct_transition": "Diagnosis_e3e3"
  },
  
  "Diagnosis_e3e3": {
      "type": "Observation",
      "category": "survey",
      "exact": { "quantity": 1 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72234-8", "display": "e3/e3" }
      ],
      "direct_transition": "APOE_Risk_E3E3"
    },

  "Set_e3e4": {
    "type": "SetAttribute", 
    "attribute": "apoe_genotype", 
    "value": "e3/e4", 
    "direct_transition": "Diagnosis_e3e4"
  },
  
  "Diagnosis_e3e4": {
      "type": "Observation",
      "category": "survey",
      "exact": { "quantity": 1 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72234-8", "display": "e3/e4" }
      ],
      "direct_transition": "APOE_Risk_E3E4"
    },

  "Set_e4e4": {
    "type": "SetAttribute", 
    "attribute": "apoe_genotype", 
    "value": "e4/e4", 
    "direct_transition": "Diagnosis_e4e4"
  },
  
  "Diagnosis_e4e4": {
      "type": "Observation",
      "category": "survey",
      "exact": { "quantity": 1 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72234-8", "display": "e4/e4" }
      ],
      "direct_transition": "APOE_Risk_E4E4"
    },

  "APOE_Risk_E4E4": {
    "type": "Simple", 
    "distributed_transition": [
	{"distribution": 0.88289, "transition": "PreAlzheimers_E4E4"},
	{"distribution": 0.11711, "transition": "Terminal"}
	],
	 "remarks": [
    "CALCOLO PROBABILITA' SVILUPPO PATOLOGIA (dati da Farrer et al., 1997):",
    "ε2/ε2 : ORgene = 0.6, ε2/ε3 : ORgene = 0.6, ε2/ε4 : ORgene = 2.6, ε3/ε4 : ORgene = 3.2 ε4/ε4 : ORgene = 14.9, (ε3/ε3 → ORgene = 1.0, è il riferimento)",
    "FORMULA:",

    "O = p0/(1-p0)  O = 0.5059569576516891 (per ottenere prevalenza target al 40%)",

    "Ogene = O * ORgene",

    "Pgene = Ogene/(1+Ogene)"
    ]
  },
  "APOE_Risk_E3E4": {
    "type": "Simple", 
    "distributed_transition": [
	{"distribution": 0.61818, "transition": "PreAlzheimers_E3E4"},
	{"distribution": 0.38182, "transition": "Terminal"}
	]
  },
  "APOE_Risk_E2E4": {
    "type": "Simple", 
    "distributed_transition": [
	{"distribution": 0.56813, "transition": "PreAlzheimers_E2E4"},
	{"distribution": 0.43187, "transition": "Terminal"}
	]
  },
  "APOE_Risk_E3E3": {
    "type": "Simple", 
    "distributed_transition": [
	{"distribution": 0.33597, "transition": "PreAlzheimers_E3E3"},
	{"distribution": 0.66403, "transition": "Terminal"}
	]
  },
  "APOE_Risk_E2E3": {
    "type": "Simple", 
    "distributed_transition": [
	{"distribution": 0.23288, "transition": "PreAlzheimers_E2E3"},
	{"distribution": 0.76712, "transition": "Terminal"}
	]
  },
  "APOE_Risk_E2E2": {
    "type": "Simple", 
    "distributed_transition": [
	{"distribution": 0.23288, "transition": "PreAlzheimers_E2E2"},
	{"distribution": 0.76712, "transition": "Terminal"}
	]
  },

  "PreAlzheimers_E4E4": {
	"type": "Delay", 
	"range": {"low": 55, "high": 70, "unit": "years"}, 
	"conditional_transition": [
		{
		   "condition": {"condition_type": "Socioeconomic Status", "category": "High"},
		   "transition": "EducationDelay_E4E4"
		},
		 {"transition": "Roadtodiagnosis"}
		]
  },

  "EducationDelay_E4E4": {
	"type": "Delay", 
	"range": {"low": 2, "high": 5, "unit": "years"}, 
	"direct_transition": "Roadtodiagnosis"
  },

  "PreAlzheimers_E3E4": {
	"type": "Delay", 
	"range": {"low": 62, "high": 75, "unit": "years"}, 
	"conditional_transition": [
		{
			"condition": {"condition_type": "Socioeconomic Status", "category": "High"}, 
			"transition": "EducationDelay_E3E4"
		},
		 {"transition": "Roadtodiagnosis"}
	]
  },
  "EducationDelay_E3E4": {
	"type": "Delay", 
	"range": {"low": 3, "high": 6, "unit": "years"}, 
	"direct_transition": "Roadtodiagnosis"
  },


  "PreAlzheimers_E2E4": {
	"type": "Delay", 
	"range": {"low": 65, "high": 78, "unit": "years"}, 
	"conditional_transition": [
		{"condition": {
			"condition_type": "Socioeconomic Status", "category": "High"}, 
			"transition": "EducationDelay_E2E4"},
			{"transition": "Roadtodiagnosis"}
	]
  },
  "EducationDelay_E2E4": {
	"type": "Delay", 
	"range": {"low": 4, "high": 7, "unit": "years"}, 
	"direct_transition": "Roadtodiagnosis"
  },


  "PreAlzheimers_E3E3": {
	"type": "Delay", 
	"range": {"low": 64, "high": 80, "unit": "years"}, 
	"conditional_transition": [
		{"condition": {
			"condition_type": "Socioeconomic Status", "category": "High"}, 
			"transition": "EducationDelay_E3E3"},
			{"transition": "Roadtodiagnosis"}
	]
  },
  "EducationDelay_E3E3": {
	"type": "Delay", 
	"range": {"low": 5, "high": 10, "unit": "years"}, 
	"direct_transition": "Roadtodiagnosis"
  },


  "PreAlzheimers_E2E3": {
	"type": "Delay", 
	"range": {"low": 70, "high": 85, "unit": "years"}, 
	"conditional_transition": [
		{"condition": {
			"condition_type": "Socioeconomic Status", "category": "High"}, 
			"transition": "EducationDelay_E2E3"},
			{"transition": "Roadtodiagnosis"}
	]
  },
  "EducationDelay_E2E3": {
	"type": "Delay", 
	"range": {"low": 6, "high": 12, "unit": "years"}, 
	"direct_transition": "Roadtodiagnosis"
  },


  "PreAlzheimers_E2E2": {
	"type": "Delay", 
	"range": {"low": 75, "high": 90, "unit": "years"}, 
	"conditional_transition": [
		{"condition": {
			"condition_type": "Socioeconomic Status", "category": "High"}, 
			"transition": "EducationDelay_E2E2"},
			{"transition": "Roadtodiagnosis"}
	]
  },
  "EducationDelay_E2E2": {
	"type": "Delay", 
	"range": {"low": 6, "high": 12, "unit": "years"}, 
	"direct_transition": "Roadtodiagnosis"
  },
    
  

   
  "Roadtodiagnosis": {
     "type": "Simple",
    "direct_transition": "Misura_HIS_Encounter"
  },
  
  
  "Misura_HIS_Encounter": {
      "type": "Encounter",
      "encounter_class": "ambulatory",
      "reason": "Type of Alzheimer's",
      "telemedicine_possibility": "possible",
      "codes": [
        { "system": "SNOMED-CT", "code": "281036007", "display": "Follow-up consultation (procedure)" }
      ],
   "direct_transition": "HIS_Observation"
  },
  "HIS_Observation": {
   "type": "Observation",
   "category": "survey",
   "codes": [
    { "system": "LOINC", "code": "LP217470-1", "display": "HIS" }
  ],
   "range": {
    "low": 0,
    "high": 12
   },
   "unit": "{score}",
   "direct_transition": "End_Misura_HIS_Encounter"
  },
  
   "End_Misura_HIS_Encounter": {
      "type": "EncounterEnd",
      "direct_transition": "Valuta_HIS"
    },
    
  "Valuta_HIS": {
   "type": "Simple",
   "conditional_transition": [
    {
      "condition": {
      	"condition_type": "Observation",
      	"codes": [
        {
          "system": "LOINC",
           "code": "LP217470-1",
           "display": "HIS"
        }
      ],
      "operator": "<",
      "value": 4
      },
      "transition": "Vascular_Encounter"
    },
    {
      "condition": {
       "condition_type": "Observation",
       "codes": [
        {
          "system": "LOINC",
           "code": "LP217470-1",
           "display": "HIS"
        }
      ],
      "operator": ">",
      "value": 7
      },
      "transition": "Alzheimer_Encounter"
    }
  ]
 },
 
 

  "Vascular_Encounter": {
      "type": "Encounter",
      "encounter_class": "ambulatory",
      "reason": "Type of Alzheimer's",
      "telemedicine_possibility": "possible",
      "codes": [
        { "system": "SNOMED-CT", "code": "281036007", "display": "Follow-up consultation (procedure)" }
      ],
   "direct_transition": "Vascular_Onset"
  },

   "Vascular_Onset": {
    "type": "ConditionOnset",
    "assign_to_attribute": "Type of Alzheimer's",
    "codes": [
     { "system": "SNOMED-CT", "code": "429998004", "display": "Vascular dementia (disorder)" }
   ],
    "direct_transition": "End_Vascular_Encounter"
 },
 
 "End_Vascular_Encounter": {
      "type": "EncounterEnd",
      "direct_transition": "ModerateDecline"
    },
  
  
    
   "Alzheimer_Encounter": {
      "type": "Encounter",
      "encounter_class": "ambulatory",
      "reason": "Type of Alzheimer's",
      "telemedicine_possibility": "possible",
      "codes": [
        { "system": "SNOMED-CT", "code": "281036007", "display": "Follow-up consultation (procedure)" }
      ],
     "remarks": [
        "This is the enounter where alzheimer's is diagnosed. ",
        "Typical life expectancy after an Alzheimer’s diagnosis is 4-to-8 years. (Alzheimer’s Association)"
      ],
   "direct_transition": "Alzheimer_Onset_Final"
  },

    "Alzheimer_Onset_Final": {
     "type": "ConditionOnset",
     "assign_to_attribute": "Type of Alzheimer's",
     "codes": [
     { "system": "SNOMED-CT", "code": "26929004", "display": "Alzheimer's disease (disorder)" }
  ],
    "direct_transition": "End_Alzheimer_Encounter"
  },
 
 "End_Alzheimer_Encounter": {
      "type": "EncounterEnd",
      "direct_transition": "Eventual_Hospice_Reason"
    },



  
    "PreEarlyOnsetAlzheimers": {
      "type": "Delay",
      "range": { "low": 40, "high": 64, "unit": "years" },
      "direct_transition": "Familiar_Encounter"
    },
    
    "Familiar_Encounter": {
      "type": "Encounter",
      "encounter_class": "ambulatory",
      "reason": "Type of Alzheimer's",
      "telemedicine_possibility": "possible",
      "codes": [
        { "system": "SNOMED-CT", "code": "281036007", "display": "Follow-up consultation (procedure)" }
      ],
     "remarks": [
        "This is the enounter where familiar alzheimer's is diagnosed. ",
        "Typical life expectancy after an Alzheimer’s diagnosis is 4-to-8 years. (Alzheimer’s Association)"
      ],
   "direct_transition": "EarlyOnsetAlzheimersOnset"
  },
    "EarlyOnsetAlzheimersOnset": {
      "type": "ConditionOnset",
      "assign_to_attribute": "Type of Alzheimer's",
      "codes": [
        { "system": "SNOMED-CT", "code": "230265002", "display": "Familiar Alzheimer's disease of early onset (disorder)" }
      ],
      "direct_transition": "End_Familiar_Encounter"
    },
    
    "End_Familiar_Encounter": {
      "type": "EncounterEnd",
      "direct_transition": "ModerateDecline"
    },



    

    "FirstObservations_Encounter": {
      "type": "Encounter",
      "encounter_class": "ambulatory",
      "direct_transition": "Lab_analysis",
      "codes": [
        { "system": "SNOMED-CT", "code": "281036007", "display": "Follow-up consultation (procedure)" }
      ],
      "reason": "Type of Alzheimer's"
    },
    "Lab_analysis": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t1_v1",
      "direct_transition": "Diagnosis_CDR_SB"
    },
    "Diagnosis_CDR_SB": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 0.5, "high": 10 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI"
    },
    "Diagnosis_NPI": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 1, "high": 30 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11"
    },
   
     "Diagnosis_ADAS_Cog_11": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 1, "high": 10 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL"
    },
     "Diagnosis_ADCS_ADL": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 50, "high": 54 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR"
    },
     "Diagnosis_CDR": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 0.5},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_GDS"
    },
     "Diagnosis_GDS": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 0, "high": 5 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "48542-5", "display": "GDS" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42"
    },
    
      "Diagnosis_CSF_AB42": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 900, "high": 1000 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau"
    },
    
     "Diagnosis_CSF_Ttau": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 200, "high": 250 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 26, "high": 28 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "Dementia_CarePlan"
   },

  "Diagnosis_MMSE_Score_Asian": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 25, "high": 27 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Dementia_CarePlan"
  },
  
   "Diagnosis_MMSE_Score_Black": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 24, "high": 26 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Dementia_CarePlan"
  },

    "Dementia_CarePlan": {
      "type": "CarePlanStart",
      "reason": "Type of Alzheimer's",
      "codes": [
        { "system": "SNOMED-CT", "code": "386257007", "display": "Dementia management (regime/therapy)" }
      ],
      "activities": [
        { "system": "SNOMED-CT", "code": "311401005", "display": "Patient education (procedure)" },
        { "system": "SNOMED-CT", "code": "710125008", "display": "Promotion of use of memory skills (procedure)" },
        { "system": "SNOMED-CT", "code": "315043002", "display": "Long term social support (regime/therapy)" }
      ],
      "direct_transition": "Delay_1"
    },
    "Delay_1": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t1"
    },
    "Lab_analysis_t1": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t1_v1",
      "direct_transition": "Diagnosis_CDR_SB_t1"
    },
    "Diagnosis_CDR_SB_t1": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 0.5, "high": 11 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t1"
    },
    "Diagnosis_NPI_t1": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 1, "high": 30 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t1"
    },
   
     "Diagnosis_ADAS_Cog_11_t1": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 2, "high": 10 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t1"
    },
     "Diagnosis_ADCS_ADL_t1": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 50, "high": 54 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t1"
    },
     "Diagnosis_CDR_t1": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 0.5},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_GDS_t1"
    },
     "Diagnosis_GDS_t1": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 1, "high": 8 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "48542-5", "display": "GDS" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t1"
    },
    
      "Diagnosis_CSF_AB42_t1": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 700, "high": 800 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t1"
    },
    
     "Diagnosis_CSF_Ttau_t1": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 260, "high": 300 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t1"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t1": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t1"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t1"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t1"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t1": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 26, "high": 28 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "Delay_2"
   },

  "Diagnosis_MMSE_Score_Asian_t1": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 25, "high": 27 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_2"
  },
  
   "Diagnosis_MMSE_Score_Black_t1": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 24, "high": 26 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_2"
  },
  "Delay_2": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t2"
    },
    "Lab_analysis_t2": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t1_v1",
      "direct_transition": "Diagnosis_CDR_SB_t2"
    },
    "Diagnosis_CDR_SB_t2": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 0.5, "high": 12 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t2"
    },
    "Diagnosis_NPI_t2": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 1, "high": 30 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t2"
    },
   
     "Diagnosis_ADAS_Cog_11_t2": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 3, "high": 10 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t2"
    },
     "Diagnosis_ADCS_ADL_t2": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 48, "high": 52 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t2"
    },
     "Diagnosis_CDR_t2": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 0.5},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_GDS_t2"
    },
     "Diagnosis_GDS_t2": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 2, "high": 9 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "48542-5", "display": "GDS" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t2"
    },
    
      "Diagnosis_CSF_AB42_t2": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 600, "high": 700 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t2"
    },
    
     "Diagnosis_CSF_Ttau_t2": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 320, "high": 350 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t2"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t2": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t2"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t2"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t2"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t2": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 25, "high": 27 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "Delay_3"
   },

  "Diagnosis_MMSE_Score_Asian_t2": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 24, "high": 26 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_3"
  },
  
   "Diagnosis_MMSE_Score_Black_t2": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 23, "high": 25 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_3"
  },
  "Delay_3": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t3"
    },
    "Lab_analysis_t3": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t1_v1",
      "direct_transition": "Diagnosis_CDR_SB_t3"
    },
    "Diagnosis_CDR_SB_t3": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 0.5, "high": 13 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t3"
    },
    "Diagnosis_NPI_t3": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 1, "high": 30 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t3"
    },
   
     "Diagnosis_ADAS_Cog_11_t3": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 2, "high": 12 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t3"
    },
     "Diagnosis_ADCS_ADL_t3": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 45, "high": 50 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t3"
    },
     "Diagnosis_CDR_t3": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 0.5},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_GDS_t3"
    },
     "Diagnosis_GDS_t3": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 3, "high": 11 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "48542-5", "display": "GDS" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t3"
    },
    
      "Diagnosis_CSF_AB42_t3": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 600, "high": 700 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t3"
    },
    
     "Diagnosis_CSF_Ttau_t3": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 350, "high": 400 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t3"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t3": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t3"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t3"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t3"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t3": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 24, "high": 26 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "FirstPrescription"
   },

  "Diagnosis_MMSE_Score_Asian_t3": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 23, "high": 25 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "FirstPrescription"
  },
  
   "Diagnosis_MMSE_Score_Black_t3": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 22, "high": 24 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "FirstPrescription"
  },
   "FirstPrescription": {
      "type": "Simple",
      "conditional_transition": [
      
        {
          "transition": "FirstPrescription4",
          "condition": {
            "condition_type": "At Least",
            "minimum": 2,
            "conditions": [
              {
                "condition_type": "Attribute",
                "attribute": "apoe_genotype",
                "operator": "==",
                "value": "e2/e2"
              },
              {
                "condition_type": "Attribute",
                "attribute": "apoe_genotype",
                "operator": "==",
                "value": "e2/e3"
              },
              {
                "condition_type": "Attribute",
                "attribute": "apoe_genotype",
                "operator": "==",
                "value": "e3/e3"
              },
              {
                "condition_type": "Date",
                "operator": ">",
                "year": 2023
              }
            ]
          }
        },
        {
          "condition": {
            "condition_type": "Date",
            "operator": ">",
            "year": 2001
          },
          "transition": "FirstPrescription1",
          "remarks": [
            "galantamine(razadyne) fda approved in 2001"
          ]
        },
        {
          "condition": {
            "condition_type": "Date",
            "operator": ">",
            "year": 1996
          },
          "transition": "FirstPrescription2",
          "remarks": [
            "donepezil(aricept) fda approved in 1996"
          ]
        },
        {
          "condition": {
            "condition_type": "Date",
            "operator": ">",
            "year": 1993
          },
          "transition": "FirstPrescription3",
          "remarks": [
            "tarine first available in 1993"
          ]
        },
        {
          "condition": {
            "condition_type": "Date",
            "operator": ">",
            "year": 1997
          },
          "transition": "FirstPrescription5",
          "remarks": [
            "rivastigmina availbale from 1997"
          ]
        },
        {
          "transition": "End_FirstObservations_Encounter",
          "remarks": [
            "before 1993 there were no specific drugs approved for Alzheimer’s by the fda"
          ]
        }
      ]
    },
    "FirstPrescription1": {
      "type": "MedicationOrder",
      "assign_to_attribute": "Alzheimer's Medication",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "310436",
          "display": "Galantamine 4 MG Oral Tablet"
        }
      ],
      "direct_transition": "Galantamine_TEAE_Check"
    },
    
    "Galantamine_TEAE_Check": {
      "type": "Simple",
      "distributed_transition": [
        { "distribution": 0.186, "transition": "Galantamine_TEAE" },  
        { "distribution": 0.814, "transition": "GalantamineDelay" }
      ]
    },
 
    "FirstPrescription2": {
      "type": "MedicationOrder",
      "assign_to_attribute": "Alzheimer's Medication",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "997223",
          "display": "Donepezil hydrochloride 10 MG Oral Tablet"
        }
      ],
      "direct_transition": "Donepezil_TEAE_Check"
    },
    
    "Donepezil_TEAE_Check": {
      "type": "Simple",
      "distributed_transition": [
        { "distribution": 0.20, "transition": "Donepezil_TEAE" },  
        { "distribution": 0.80, "transition": "DonepezilDelay" }
      ]
    },
    "FirstPrescription3": {
      "type": "MedicationOrder",
      "assign_to_attribute": "Alzheimer's Medication",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "313185",
          "display": "Tacrine 10 MG Oral Capsule"
        }
      ],
      "direct_transition": "Tacrine_TEAE_Check"
    },
    
    "Tacrine_TEAE_Check": {
      "type": "Simple",
      "distributed_transition": [
        { "distribution": 0.50, "transition": "Tacrina_TEAE" },  
        { "distribution": 0.50, "transition": "TacrineDelay" }
      ]
    },
     "FirstPrescription4": {
      "type": "MedicationOrder",
      "assign_to_attribute": "Alzheimer's Medication",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "2608323",
          "display": "Lecanemab 10 MG/Kg Injection"
        }
      ],
      "direct_transition": "Lecanemab_TEAE_Check"
    },
    
    "Lecanemab_TEAE_Check": {
      "type": "Simple",
      "distributed_transition": [
        { "distribution": 0.105, "transition": "Lecanemab_TEAE" },  
        { "distribution": 0.895, "transition": "LecanemabDelay" }
      ]
    },
     "FirstPrescription5": {
      "type": "MedicationOrder",
      "assign_to_attribute": "Alzheimer's Medication",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "2608324",
          "display": "Rivastigmina 1,5 MG oral"
        }
      ],
      "direct_transition": "Rivastigmina_TEAE_Check"
    },
    
    "Rivastigmina_TEAE_Check": {
      "type": "Simple",
      "distributed_transition": [
        { "distribution": 0.193, "transition": "Rivastigmina_TEAE" },  
        { "distribution": 0.807, "transition": "RivastigminaDelay" }
      ]
    },
    
     "LecanemabDelay": {
	"type": "Delay", 
	"range": {"low": 2, "high": 3, "unit": "years"}, 
	"direct_transition": "End_FirstObservations_Encounter"
     },
     "RivastigminaDelay": {
	"type": "Delay", 
	"range": {"low": 3, "high": 6, "unit": "months"}, 
	"direct_transition": "End_FirstObservations_Encounter"
     },
     "TacrineDelay": {
	"type": "Delay", 
	"range": {"low": 6, "high": 12, "unit": "months"}, 
	"direct_transition": "End_FirstObservations_Encounter"
     },
     "GalantamineDelay": {
	"type": "Delay", 
	"range": {"low": 6, "high": 12, "unit": "months"}, 
	"direct_transition": "End_FirstObservations_Encounter"
     },
     "DonepezilDelay": {
	"type": "Delay", 
	"range": {"low": 6, "high": 24, "unit": "months"}, 
	"direct_transition": "End_FirstObservations_Encounter"
     },  
     "Galantamine_TEAE": {
      "type": "ConditionOnset",
      "codes": [
        { "system": "SNOMED-CT", "code": "422587007", "display": "Nausea" }
       ],
       "direct_transition": "MedicationStop_Galantamine"
     },
     "Donepezil_TEAE": {
      "type": "ConditionOnset",
      "codes": [
        { "system": "SNOMED-CT", "code": "422587007", "display": "Nausea" }
       ],
       "direct_transition": "MedicationStop_Donepezil"
     },
     "Lecanemab_TEAE": {
      "type": "ConditionOnset",
      "codes": [
        { "system": "SNOMED-CT", "code": "703276005", "display": "ARIA-E" }
       ],
       "direct_transition": "MedicationStop_Lecanemab"
     },
     "Rivastigmina_TEAE": {
      "type": "ConditionOnset",
      "codes": [
        { "system": "SNOMED-CT", "code": "422587007", "display": "Nausea" }
       ],
       "direct_transition": "MedicationStop_Rivastigmina"
     },
     "Tacrina_TEAE": {
      "type": "ConditionOnset",
      "codes": [
        { "system": "SNOMED-CT", "code": "400064005", "display": "Hepatotoxicity" }
       ],
       "direct_transition": "MedicationStop_Tacrine"
     },
     
     "MedicationStop_Donepezil": {
      "type": "MedicationEnd",
      "codes": [ 
         {
          "system": "RxNorm",
          "code": "997223",
          "display": "Donepezil hydrochloride 10 MG Oral Tablet"
         }
        ],
      "direct_transition": "End_Nausea_DON"
     },
     
      "End_Nausea_DON": {
      "type": "ConditionEnd",
      "condition_onset": "Donepezil_TEAE",
      "direct_transition": "End_FirstObservations_Encounter"
     },
     
     "MedicationStop_Galantamine": {
      "type": "MedicationEnd",
      "codes": [ 
         {
          "system": "RxNorm",
          "code": "310436",
          "display": "Galantamine 4 MG Oral Tablet"
         }
        ],
      "direct_transition": "End_Nausea_GAL"
     },
     
     "End_Nausea_GAL": {
      "type": "ConditionEnd",
      "condition_onset": "Galantamine_TEAE",
      "direct_transition": "End_FirstObservations_Encounter"
     },
     
     "MedicationStop_Rivastigmina": {
      "type": "MedicationEnd",
      "codes": [ 
         {
          "system": "RxNorm",
          "code": "2608324",
          "display": "Rivastigmina 1,5 MG oral"
         }
        ],
      "direct_transition": "End_Nausea_RIV"
     },
     
      "End_Nausea_RIV": {
      "type": "ConditionEnd",
      "condition_onset": "Rivastigmina_TEAE",
      "direct_transition": "End_FirstObservations_Encounter"
     },
     
     "MedicationStop_Lecanemab": {
      "type": "MedicationEnd",
      "codes": [ 
         {
          "system": "RxNorm",
          "code": "2608323",
          "display": "Lecanemab 10 MG/Kg Injection"
         }
        ],
      "direct_transition": "End_Nausea_LEC"
     },
     
      "End_Nausea_LEC": {
      "type": "ConditionEnd",
      "condition_onset": "Lecanemab_TEAE",
      "direct_transition": "End_FirstObservations_Encounter"
     },
     
     "MedicationStop_Tacrine": {
      "type": "MedicationEnd",
      "codes": [ 
         {
          "system": "RxNorm",
          "code": "313185",
          "display": "Tacrine 10 MG Oral Capsule"
         }
        ],
      "direct_transition": "End_Nausea_TAC"
     },
     
      "End_Nausea_TAC": {
      "type": "ConditionEnd",
      "condition_onset": "Tacrina_TEAE",
      "direct_transition": "End_FirstObservations_Encounter"
     },

     "ModerateDecline": {
      "type": "Delay",
      "range": {
        "low": 1,
        "high": 2,
        "unit": "months"
      },
      "remarks": [
        "4. Moderate decline, or mild alzheimer's has a mean duration of 2 years.",
        "The diagnosis of alzheimer's can be made with considerable accuracy in this stage",
        "https://www.alzinfo.org/understand-alzheimers/clinical-stages-of-alzheimers/"
      ],
      "conditional_transition": [
        {
          "condition": {
            "condition_type": "Not",
            "condition": {
              "condition_type": "PriorState",
              "name": "FirstObservations_Encounter"
            }
          },
          "transition": "FirstObservations_Encounter"
        },
       
        {
          "transition": "ModeratelySevere_Encounter"
        }
      ]
    },
    

    "ModeratelySevere_Encounter": {
      "type": "Encounter",
      "encounter_class": "ambulatory",
      "reason": "Type of Alzheimer's",
      "telemedicine_possibility": "possible",
      "codes": [
        { "system": "SNOMED-CT", "code": "281036007", "display": "Follow-up consultation (procedure)" }
      ],
      "direct_transition": "Lab_analysis2"
    },
    "Lab_analysis2": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t2_v1",
      "direct_transition": "ModeratelySevere_CDR_SB"
    },
    "ModeratelySevere_CDR_SB": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 4, "high": 12 },
      "unit": "{score}",
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "ModeratelySevere_NPI"
    },
    "ModeratelySevere_NPI": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 1, "high": 50 },
      "unit": "{score}",
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "ModeratelySevere_ADAS_Cog_11"
    },
    
   

    "ModeratelySevere_ADAS_Cog_11": {
	"type": "Observation",
	"category": "survey",
	"range": { "low": 12, "high": 40 },
	"unit": "{score}",
	"remarks": [

	],
	"codes": [
	{ "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
	],
	"direct_transition": "ModeratelySevere_ADCS_ADL"
	},
    "ModeratelySevere_ADCS_ADL": {
	"type": "Observation",
	"category": "survey",
	"range": { "low": 40, "high": 45 },
	"unit": "{score}",
	"remarks": [

	],
	"codes": [
	{ "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
	],
	"direct_transition": "ModeratelySevere_CDR"
	},
    "ModeratelySevere_CDR": {
	"type": "Observation",
	"category": "survey",
	"exact": {"quantity": 1},
	"unit": "{score}",
	"remarks": [

	],
	"codes": [
	{ "system": "LOINC", "code": "72088-8", "display": "CDR" }
	],
	"direct_transition": "ModeratelySevere_GDS"
	},
    "ModeratelySevere_GDS": {
	"type": "Observation",
	"category": "survey",
	"range": { "low": 8, "high": 15 },
	"unit": "{score}",
	"remarks": [

	],
	"codes": [
	{ "system": "LOINC", "code": "48542-5", "display": "GDS" }
	],
	"direct_transition": "ModeratelySevere_CSF_AB42"
	},
	 
    "ModeratelySevere_CSF_AB42": {
      "type": "Observation",
      "category": "imaging",
      "range": { "low": 550, "high": 600 },
      "unit": "pg/ml",
      "remarks": [

       ],
      "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
      "direct_transition": "ModeratelySevere_CSF_Ttau"
    },
    
    "ModeratelySevere_CSF_Ttau": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 420, "high": 500 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "ModeratelySevere_FDG_PET_SUVR"
    },
    
     "ModeratelySevere_FDG_PET_SUVR": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 0.395, "high": 0.523 },
       "unit": "{score}",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "87907-2", "display": "FDG-PET SUVR" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity2"
    },
      "Diagnosis_MMSE_Score_Ethnicity2": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian2"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White2"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black2"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White2": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 22, "high": 24 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "conditional_transition": [
        {
          "condition": {
            "condition_type": "Attribute",
            "attribute": "Alzheimer's Medication",
            "operator": "is not nil"
          },
          "transition": "EndFirstPrescription"
        },
        {
          "transition": "Delay_4"
        }
      ]
   },

  "Diagnosis_MMSE_Score_Asian2": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 21, "high": 23 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "conditional_transition": [
        {
          "condition": {
            "condition_type": "Attribute",
            "attribute": "Alzheimer's Medication",
            "operator": "is not nil"
          },
          "transition": "EndFirstPrescription"
        },
        {
          "transition": "Delay_4"
        }
      ]
  },
  
   "Diagnosis_MMSE_Score_Black2": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 20, "high": 22 },
    "unit": "{score}",
    "remarks": [
        "The maximum MMSE score is 30 points. A score of 20 to 24 suggests mild dementia, ",
        "13 to 20 suggests moderate dementia, and less than 12 indicates severe dementia",
        "http://www.alz.org/alzheimers_disease_steps_to_diagnosis.asp"
      ],
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "conditional_transition": [
        {
          "condition": {
            "condition_type": "Attribute",
            "attribute": "Alzheimer's Medication",
            "operator": "is not nil"
          },
          "transition": "EndFirstPrescription"
        },
        {
          "transition": "Delay_4"
        }
      ]
   },
  
    "EndFirstPrescription": {
      "type": "MedicationEnd",
      "referenced_by_attribute": "Alzheimer's Medication",
      "direct_transition": "Delay_4"
      
    },
    "Delay_4": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t4"
    },
    "Lab_analysis_t4": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t2_v1",
      "direct_transition": "Diagnosis_CDR_SB_t4"
    },
    "Diagnosis_CDR_SB_t4": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 4, "high": 13 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t4"
    },
    "Diagnosis_NPI_t4": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 1, "high": 50 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t4"
    },
   
     "Diagnosis_ADAS_Cog_11_t4": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 13, "high": 40 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t4"
    },
     "Diagnosis_ADCS_ADL_t4": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 40, "high": 45 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t4"
    },
     "Diagnosis_CDR_t4": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 1},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_GDS_t4"
    },
     "Diagnosis_GDS_t4": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 8, "high": 20 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "48542-5", "display": "GDS" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t4"
    },
    
      "Diagnosis_CSF_AB42_t4": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 500, "high": 550 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t4"
    },
    
     "Diagnosis_CSF_Ttau_t4": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 520, "high": 580 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t4"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t4": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t4"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t4"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t4"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t4": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 22, "high": 24 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "Delay_5"
   },

  "Diagnosis_MMSE_Score_Asian_t4": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 21, "high": 23 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_5"
  },
  
   "Diagnosis_MMSE_Score_Black_t4": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 20, "high": 22 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_5"
  },
  "Delay_5": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t5"
    },
    "Lab_analysis_t5": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t2_v1",
      "direct_transition": "Diagnosis_CDR_SB_t5"
    },
    "Diagnosis_CDR_SB_t5": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 4, "high": 14 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t5"
    },
    "Diagnosis_NPI_t5": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 1, "high": 50 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t5"
    },
    
     "Diagnosis_ADAS_Cog_11_t5": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 14, "high": 40 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t5"
    },
     "Diagnosis_ADCS_ADL_t5": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 40, "high": 45 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t5"
    },
     "Diagnosis_CDR_t5": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 1},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_GDS_t5"
    },
     "Diagnosis_GDS_t5": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 10, "high": 25 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "48542-5", "display": "GDS" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t5"
    },
    
      "Diagnosis_CSF_AB42_t5": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 500, "high": 550 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t5"
    },
    
     "Diagnosis_CSF_Ttau_t5": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 580, "high": 600 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t5"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t5": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t5"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t5"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t5"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t5": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 18, "high": 22 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "Delay_6"
   },

  "Diagnosis_MMSE_Score_Asian_t5": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 17, "high": 21 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_6"
  },
  
   "Diagnosis_MMSE_Score_Black_t5": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 16, "high": 20 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_6"
  },
  "Delay_6": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t6"
    },
    "Lab_analysis_t6": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t2_v1",
      "direct_transition": "Diagnosis_CDR_SB_t6"
    },
    "Diagnosis_CDR_SB_t6": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 4, "high": 15 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t6"
    },
    "Diagnosis_NPI_t6": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 1, "high": 50 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t6"
    },
   
     "Diagnosis_ADAS_Cog_11_t6": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 15, "high": 42 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t6"
    },
     "Diagnosis_ADCS_ADL_t6": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 38, "high": 44 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t6"
    },
     "Diagnosis_CDR_t6": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 1},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_GDS_t6"
    },
     "Diagnosis_GDS_t6": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 13, "high": 30 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "48542-5", "display": "GDS" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t6"
    },
    
      "Diagnosis_CSF_AB42_t6": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 500, "high": 550 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t6"
    },
    
     "Diagnosis_CSF_Ttau_t6": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 580, "high": 600 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t6"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t6": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t6"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t6"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t6"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t6": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 16, "high": 20 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "SecondPrescription"
   },

  "Diagnosis_MMSE_Score_Asian_t6": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 15, "high": 19 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "SecondPrescription"
  },
  
   "Diagnosis_MMSE_Score_Black_t6": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 14, "high": 18 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "SecondPrescription"
  },
    "SecondPrescription": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
            "condition_type": "Date",
            "operator": ">",
            "year": 2014
          },
          "transition": "SecondPrescription1",
          "remarks": [
            "memantine+donepezil(namzaric) fda approved in 2014"
          ]
        },
        {
          "condition": {
            "condition_type": "Date",
            "operator": ">",
            "year": 2003
          },
          "transition": "SecondPrescription2",
          "remarks": [
            "memantine(namenda) fda approved in 2003"
          ]
        },
        {
          "condition": {
            "condition_type": "Date",
            "operator": ">",
            "year": 1997
          },
          "transition": "SecondPrescription4",
          "remarks": [
            "rivastigmina availbale from 1997"
          ]
        },
        {
          "condition": {
            "condition_type": "Date",
            "operator": ">",
            "year": 1996
          },
          "transition": "SecondPrescription3",
          "remarks": [
            "donepezil(aricept) fda approved in 1996"
          ]
        },
        {
          "transition": "End_ModeratelySevere_Encounter"
        }
      ]
    },
    "SecondPrescription1": {
      "type": "MedicationOrder",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "1599803",
          "display": "24 HR Donepezil hydrochloride 10 MG / Memantine hydrochloride 28 MG Extended Release Oral Capsule"
        }
      ],
      "direct_transition": "DonepezilMemantine_TEAE_Check"
    },
    "DonepezilMemantine_TEAE_Check": {
      "type": "Simple",
      "distributed_transition": [
        { "distribution": 0.286, "transition": "DonepezilMemantine_TEAE" },  
        { "distribution": 0.714, "transition": "DonepezilMemantineDelay" }
      ]
    },
    "SecondPrescription2": {
      "type": "MedicationOrder",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "996740",
          "display": "Memantine hydrochloride 2 MG/ML Oral Solution"
        }
      ],
      "direct_transition": "Memantine_TEAE_Check"
    },
    "Memantine_TEAE_Check": {
      "type": "Simple",
      "distributed_transition": [
        { "distribution": 0.086, "transition": "Memantine_TEAE" },  
        { "distribution": 0.914, "transition": "MemantineDelay" }
      ]
    },
    "SecondPrescription3": {
      "type": "MedicationOrder",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "1100184",
          "display": "Donepezil hydrochloride 23 MG Oral Tablet"
        }
      ],
      "direct_transition": "Donepezil_TEAE_Check2"
    },
    "Donepezil_TEAE_Check2": {
      "type": "Simple",
      "distributed_transition": [
        { "distribution": 0.20, "transition": "Donepezil_TEAE2" },  
        { "distribution": 0.80, "transition": "DonepezilDelay2" }
      ]
    },
    
     "SecondPrescription4": {
      "type": "MedicationOrder",
      "assign_to_attribute": "Alzheimer's Medication",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "2608325",
          "display": "Rivastigmina 3 MG oral"
        }
      ],
      "direct_transition": "Rivastigmina_TEAE_Check2"
    },
    "Rivastigmina_TEAE_Check2": {
      "type": "Simple",
      "distributed_transition": [
        { "distribution": 0.193, "transition": "Rivastigmina_TEAE2" },  
        { "distribution": 0.807, "transition": "RivastigminaDelay2" }
      ]
    },
    
    "DonepezilMemantineDelay": {
	"type": "Delay", 
	"range": {"low": 6, "high": 24, "unit": "months"}, 
	"direct_transition": "End_ModeratelySevere_Encounter"
     },
     "RivastigminaDelay2": {
	"type": "Delay", 
	"range": {"low": 3, "high": 6, "unit": "months"}, 
	"direct_transition": "End_ModeratelySevere_Encounter"
     },
     "MemantineDelay": {
	"type": "Delay", 
	"range": {"low": 6, "high": 12, "unit": "months"}, 
	"direct_transition": "End_ModeratelySevere_Encounter"
     },
     "DonepezilDelay2": {
	"type": "Delay", 
	"range": {"low": 6, "high": 24, "unit": "months"}, 
	"direct_transition": "End_ModeratelySevere_Encounter"
     },
     
     "Memantine_TEAE": {
      "type": "ConditionOnset",
      "codes": [
        { "system": "SNOMED-CT", "code": "404640003", "display": "Dizziness" }
       ],
       "direct_transition": "MedicationStop_Memantine"
     },
     "Donepezil_TEAE2": {
      "type": "ConditionOnset",
      "codes": [
        { "system": "SNOMED-CT", "code": "422587007", "display": "Nausea" }
       ],
       "direct_transition": "MedicationStop_Donepezil2"
     },
     "DonepezilMemantine_TEAE": {
      "type": "ConditionOnset",
      "codes": [
        { "system": "SNOMED-CT", "code": "703276005", "display": "Nausea-Dizziness" }
       ],
       "direct_transition": "MedicationStop_DonepezilMemantine"
     },
     "Rivastigmina_TEAE2": {
      "type": "ConditionOnset",
      "codes": [
        { "system": "SNOMED-CT", "code": "422587007", "display": "Nausea" }
       ],
       "direct_transition": "MedicationStop_Rivastigmina2"
     },
         
     "MedicationStop_Donepezil2": {
      "type": "MedicationEnd",
      "codes": [ 
         {
          "system": "RxNorm",
          "code": "1100184",
          "display": "Donepezil hydrochloride 23 MG Oral Tablet"
         }
        ],
      "direct_transition": "End_adverse_DON2"
     },
     
     "End_adverse_DON2": {
      "type": "ConditionEnd",
      "condition_onset": "Donepezil_TEAE2",
      "direct_transition": "End_ModeratelySevere_Encounter"
     },
     
     "MedicationStop_DonepezilMemantine": {
      "type": "MedicationEnd",
      "codes": [ 
         {
          "system": "RxNorm",
          "code": "1599803",
          "display": "24 HR Donepezil hydrochloride 10 MG / Memantine hydrochloride 28 MG Extended Release Oral Capsule"
         }
        ],
      "direct_transition": "End_adverse_DONMEM"
     },
     
     "End_adverse_DONMEM": {
      "type": "ConditionEnd",
      "condition_onset": "DonepezilMemantine_TEAE",
      "direct_transition": "End_ModeratelySevere_Encounter"
     },
     
     
     "MedicationStop_Rivastigmina2": {
      "type": "MedicationEnd",
      "codes": [ 
         {
          "system": "RxNorm",
          "code": "2608325",
          "display": "Rivastigmina 3 MG oral"
         }
        ],
      "direct_transition": "End_adverse_RIV2"
     },
     
     "End_adverse_RIV2": {
      "type": "ConditionEnd",
      "condition_onset": "Rivastigmina_TEAE2",
      "direct_transition": "End_ModeratelySevere_Encounter"
     },
     
     
     "MedicationStop_Memantine": {
      "type": "MedicationEnd",
      "codes": [ 
         {
          "system": "RxNorm",
          "code": "996740",
          "display": "Memantine hydrochloride 2 MG/ML Oral Solution"
         }
        ],
      "direct_transition": "End_adverse_MEM"
     },
     
     "End_adverse_MEM": {
      "type": "ConditionEnd",
      "condition_onset": "Memantine_TEAE",
      "direct_transition": "End_ModeratelySevere_Encounter"
     },
        
    "End_ModeratelySevere_Encounter": {
      "type": "EncounterEnd",
      "direct_transition": "ModeratelySevereDecline"
    },
    "ModeratelySevereDecline": {
      "type": "Delay",
      "range": {
        "low": 6,
        "high": 18,
        "unit": "months"
      },
      "remarks": [
        "5. Moderately severe decline, aka mid-stage or moderate alzheimer's has a mean duration about 1.5 yrs",
        "https://www.alzinfo.org/understand-alzheimers/clinical-stages-of-alzheimers/"
      ],
      "direct_transition": "Severe_Encounter"
    },

    "Severe_Encounter": {
      "type": "Encounter",
      "encounter_class": "ambulatory",
      "reason": "Type of Alzheimer's",
      "codes": [
        { "system": "SNOMED-CT", "code": "281036007", "display": "Follow-up consultation (procedure)" }
      ],
      "direct_transition": "Lab_analysis3"
    },
    "Lab_analysis3": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t3_v1",
      "direct_transition": "Severe_CDR_SB"
    },
    "Severe_CDR_SB": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 6, "high": 15 },
      "unit": "{score}",
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Severe_NPI"
    },
    
    "Severe_NPI": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 40, "high": 70 },
      "unit": "{score}",
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Severe_ADAS_Cog_11"
    },
    
    

    "Severe_ADAS_Cog_11": {
	"type": "Observation",
	"category": "survey",
	"range": { "low": 23, "high": 60 },
	"unit": "{score}",
	"remarks": [

	],
	"codes": [
	{ "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
	],
	"direct_transition": "Severe_ADCS_ADL"
	},
	
    "Severe_ADCS_ADL": {
	"type": "Observation",
	"category": "survey",
	"range": { "low": 33, "high": 38 },
	"unit": "{score}",
	"remarks": [

	],
	"codes": [
	{ "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
	],
	"direct_transition": "Severe_CDR"
	},
    "Severe_CDR": {
	"type": "Observation",
	"category": "survey",
	"exact": {"quantity": 2},
	"unit": "{score}",
	"remarks": [

	],
	"codes": [
	{ "system": "LOINC", "code": "72088-8", "display": "CDR" }
	],
	"direct_transition": "Severe_CSF_AB42"
	},
	
    "Severe_CSF_AB42": {
      "type": "Observation",
      "category": "imaging",
      "range": { "low": 400, "high": 500 },
      "unit": "pg/ml",
      "remarks": [

       ],
      "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
      "direct_transition": "Severe_CSF_Ttau"
    },
    
    "Severe_CSF_Ttau": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 600, "high": 640 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity3"
    },
      "Diagnosis_MMSE_Score_Ethnicity3": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian3"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White3"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black3"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White3": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 14, "high": 20 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
      "remarks": [
        "The maximum MMSE score is 30 points. A score of 20 to 24 suggests mild dementia, ",
        "13 to 20 suggests moderate dementia, and less than 12 indicates severe dementia",
        "http://www.alz.org/alzheimers_disease_steps_to_diagnosis.asp"
      ],
     "direct_transition": "Delay_7"
   },

  "Diagnosis_MMSE_Score_Asian3": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 13, "high": 19 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_7"
    },
  
   "Diagnosis_MMSE_Score_Black3": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 12, "high": 18 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_7"
    },
    
    "Delay_7": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t7"
    },
    "Lab_analysis_t7": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t3_v1",
      "direct_transition": "Diagnosis_CDR_SB_t7"
    },
    "Diagnosis_CDR_SB_t7": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 6, "high": 16 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t7"
    },
    "Diagnosis_NPI_t7": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 40, "high": 71 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t7"
    },
    
     "Diagnosis_ADAS_Cog_11_t7": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 23, "high": 61 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t7"
    },
     "Diagnosis_ADCS_ADL_t7": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 33, "high": 38 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t7"
    },
     "Diagnosis_CDR_t7": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 2},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t7"
    },
    
      "Diagnosis_CSF_AB42_t7": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 400, "high": 500 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t7"
    },
    
     "Diagnosis_CSF_Ttau_t7": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 650, "high": 700 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t7"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t7": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t7"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t7"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t7"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t7": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 14, "high": 20 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "Delay_8"
   },

  "Diagnosis_MMSE_Score_Asian_t7": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 13, "high": 19 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_8"
  },
  
   "Diagnosis_MMSE_Score_Black_t7": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 12, "high": 18 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_8"
  },
  "Delay_8": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t8"
    },
    "Lab_analysis_t8": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t3_v1",
      "direct_transition": "Diagnosis_CDR_SB_t8"
    },
    "Diagnosis_CDR_SB_t8": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 6, "high": 17 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t8"
    },
    "Diagnosis_NPI_t8": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 40, "high": 70 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t8"
    },
   
     "Diagnosis_ADAS_Cog_11_t8": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 23, "high": 62 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t8"
    },
     "Diagnosis_ADCS_ADL_t8": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 33, "high": 38 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t8"
    },
     "Diagnosis_CDR_t8": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 2},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t8"
    },
    
    
      "Diagnosis_CSF_AB42_t8": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 400, "high": 500 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t8"
    },
    
     "Diagnosis_CSF_Ttau_t8": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 710, "high": 790 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t8"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t8": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t8"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t8"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t8"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t8": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 14, "high": 20 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "Delay_9"
   },

  "Diagnosis_MMSE_Score_Asian_t8": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 13, "high": 19 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_9"
  },
  
   "Diagnosis_MMSE_Score_Black_t8": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 12, "high": 18 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_9"
  },
  "Delay_9": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t9"
    },
    "Lab_analysis_t9": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t3_v1",
      "direct_transition": "Diagnosis_CDR_SB_t9"
    },
    "Diagnosis_CDR_SB_t9": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 6, "high": 18 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t9"
    },
    "Diagnosis_NPI_t9": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 40, "high": 73 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t9"
    },
   
     "Diagnosis_ADAS_Cog_11_t9": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 23, "high": 63 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t9"
    },
     "Diagnosis_ADCS_ADL_t9": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 30, "high": 33 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t9"
    },
     "Diagnosis_CDR_t9": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 2},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t9"
    },
    
    
      "Diagnosis_CSF_AB42_t9": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 400, "high": 500 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t9"
    },
    
     "Diagnosis_CSF_Ttau_t9": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 790, "high": 800 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t9"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t9": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t9"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t9"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t9"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t9": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 13, "high": 18 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "End_Severe_Encounter"
   },

  "Diagnosis_MMSE_Score_Asian_t9": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 12, "high": 17 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "End_Severe_Encounter"
  },
  
   "Diagnosis_MMSE_Score_Black_t9": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 11, "high": 16 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "End_Severe_Encounter"
  },
   
    "End_Severe_Encounter": {
      "type": "EncounterEnd",
      "direct_transition": "SevereDecline"
    },
    "SevereDecline": {
      "type": "Delay",
      "range": {
        "low": 11,
        "high": 31,
        "unit": "months"
      },
      "remarks": [
        "6. Severe decline, or moderately severe Alzheimer's contains 5 defined substages, the total duration approximately 2.5 yrs"
      ],
      "direct_transition": "VerySevere_Encounter"
    },

    "VerySevere_Encounter": {
      "type": "Encounter",
      "encounter_class": "ambulatory",
      "reason": "Type of Alzheimer's",
      "codes": [
        { "system": "SNOMED-CT", "code": "281036007", "display": "Follow-up consultation (procedure)" }
      ],
      "direct_transition": "Lab_analysis4"
    },
    "Lab_analysis4": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t4_v1",
      "direct_transition": "VerySevere_CDR_SB"
    },
    "VerySevere_CDR_SB": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 10, "high": 18 },
      "unit": "{score}",
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "VerySevere_NPI"
    },
    "VerySevere_NPI": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 70, "high": 120 },
      "unit": "{score}",
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "VerySevere_ADAS_Cog_11"
    },
  
    "VerySevere_ADAS_Cog_11": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 35, "high": 70 },
      "unit": "{score}",
      "remarks": [

	],
      "codes": [
	{ "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
	],
      "direct_transition": "VerySevere_ADCS_ADL"
	},
    "VerySevere_ADCS_ADL": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 25, "high": 30 },
     "unit": "{score}",
     "remarks": [

      ],
     "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
       ],
     "direct_transition": "VerySevere_CDR"
    },
    "VerySevere_CDR": {
	"type": "Observation",
	"category": "survey",
	"exact": {"quantity": 3},
	"unit": "{score}",
	"remarks": [

	],
	"codes": [
	{ "system": "LOINC", "code": "72088-8", "display": "CDR" }
	],
	"direct_transition": "VerySevere_CSF_AB42"
    },
    
    "VerySevere_CSF_AB42": {
     "type": "Observation",
     "category": "imaging",
     "range": { "low": 350, "high": 400 },
     "unit": "pg/ml",
     "remarks": [

      ],
     "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
     "direct_transition": "VerySevere_CSF_Ttau"
    },
    
    "VerySevere_CSF_Ttau": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 810, "high": 850 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity4"
    },
      "Diagnosis_MMSE_Score_Ethnicity4": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian4"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White4"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black4"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White4": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 12, "high": 15 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
      "remarks": [
        "The maximum MMSE score is 30 points. A score of 20 to 24 suggests mild dementia, ",
        "13 to 20 suggests moderate dementia, and less than 12 indicates severe dementia",
        "http://www.alz.org/alzheimers_disease_steps_to_diagnosis.asp"
      ],
     "direct_transition": "Delay_10"
   },

  "Diagnosis_MMSE_Score_Asian4": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 11, "high": 14 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_10"
    },
  
   "Diagnosis_MMSE_Score_Black4": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 10, "high": 13 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_10"
    },
    
   "Delay_10": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t10"
    },
    "Lab_analysis_t10": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t4_v1",
      "direct_transition": "Diagnosis_CDR_SB_t10"
    },
    "Diagnosis_CDR_SB_t10": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 10, "high": 18 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t10"
    },
    "Diagnosis_NPI_t10": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 70, "high": 120 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t10"
    },
  
     "Diagnosis_ADAS_Cog_11_t10": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 35, "high": 70 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t10"
    },
     "Diagnosis_ADCS_ADL_t10": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 25, "high": 30 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t10"
    },
     "Diagnosis_CDR_t10": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 3},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t10"
    },
    
    
      "Diagnosis_CSF_AB42_t10": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 200, "high": 350 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t10"
    },
    
     "Diagnosis_CSF_Ttau_t10": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 850, "high": 870 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t10"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t10": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t10"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t10"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t10"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t10": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 10, "high": 14 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "Delay_11"
   },

  "Diagnosis_MMSE_Score_Asian_t10": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 9, "high": 13 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_11"
  },
  
   "Diagnosis_MMSE_Score_Black_t10": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 8, "high": 12 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_11"
  },
  "Delay_11": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t11"
    },
    "Lab_analysis_t11": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t4_v1",
      "direct_transition": "Diagnosis_CDR_SB_t11"
    },
    "Diagnosis_CDR_SB_t11": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 10, "high": 18 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t11"
    },
    "Diagnosis_NPI_t11": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 70, "high": 130 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t11"
    },
   
     "Diagnosis_ADAS_Cog_11_t11": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 35, "high": 70 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t11"
    },
     "Diagnosis_ADCS_ADL_t11": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 20, "high": 25 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t11"
    },
     "Diagnosis_CDR_t11": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 3},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t11"
    },
        
      "Diagnosis_CSF_AB42_t11": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 100, "high": 200 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t11"
    },
    
     "Diagnosis_CSF_Ttau_t11": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 870, "high": 900 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t11"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t11": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t11"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t11"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t11"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t11": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 8, "high": 12 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "Delay_12"
   },

  "Diagnosis_MMSE_Score_Asian_t11": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 7, "high": 11 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_12"
  },
  
   "Diagnosis_MMSE_Score_Black_t11": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 6, "high": 10 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "Delay_12"
  },
  "Delay_12": {
      "type": "Delay",
      "exact": { "quantity": 1, "unit": "months" },
      "remarks": [
      ],
      "direct_transition": "Lab_analysis_t12"
    },
    "Lab_analysis_t12": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t4_v1",
      "direct_transition": "Diagnosis_CDR_SB_t12"
    },
    "Diagnosis_CDR_SB_t12": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 10, "high": 18 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_t12"
    },
    "Diagnosis_NPI_t12": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 70, "high": 140 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_t12"
    },
    
     "Diagnosis_ADAS_Cog_11_t12": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 35, "high": 70 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_t12"
    },
     "Diagnosis_ADCS_ADL_t12": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 10, "high": 20 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_t12"
    },
     "Diagnosis_CDR_t12": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 3},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_t12"
    },
  
    
      "Diagnosis_CSF_AB42_t12": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 100, "high": 200 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_t12"
    },
    
     "Diagnosis_CSF_Ttau_t12": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 870, "high": 900 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_Ethnicity_t12"
    },
       
    "Diagnosis_MMSE_Score_Ethnicity_t12": {
      "type": "Simple",
      "conditional_transition": [
        {
          "condition": {
           "condition_type": "Race",
            "race": "Asian"
           },
         "transition": "Diagnosis_MMSE_Score_Asian_t12"
        },
        {
         "condition": {
           "condition_type": "Race",
           "race": "White"
          },
        "transition": "Diagnosis_MMSE_Score_White_t12"
       },
       {
        "condition": {
          "condition_type": "Race",
          "race": "Black"
         },
        "transition": "Diagnosis_MMSE_Score_Black_t12"
       }
     ]
    },

   "Diagnosis_MMSE_Score_White_t12": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 4, "high": 10 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "End_VerySevere_Encounter"
   },

  "Diagnosis_MMSE_Score_Asian_t12": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 3, "high": 9 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "End_VerySevere_Encounter"
  },
  
   "Diagnosis_MMSE_Score_Black_t12": {
    "type": "Observation",
    "category": "survey",
    "range": { "low": 2, "high": 8 },
    "unit": "{score}",
    "codes": [
     { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
    ],
    "direct_transition": "End_VerySevere_Encounter"
  },
   
    "End_VerySevere_Encounter": {
      "type": "EncounterEnd",
      "direct_transition": "VerySevereDecline"
    },
    "VerySevereDecline": {
      "type": "Delay",
      "range": {
        "low": 1,
        "high": 2,
        "unit": "months"
      },
      "remarks": [
        "7. Very severe decline, aka late-stage or severe alzheimer's contains 6 functional substages, each with a mean duration ~1 yr",
        "https://www.alzinfo.org/understand-alzheimers/clinical-stages-of-alzheimers/"
      ],
      "distributed_transition": [
        {
          "distribution": 0.16,
          "transition": "Pneumonia"
        },
        {
          "distribution": 0.16,
          "transition": "Death"
        },
        {
          "distribution": 0.68,
          "transition": "VerySevereDecline"
        }
      ]
    },

    "Pneumonia": {
      "type": "ConditionOnset",
      "codes": [
        {
          "system": "SNOMED-CT",
          "code": "233604007",
          "display": "Pneumonia (disorder)"
        }
      ],
      "remarks": [
        "Pneumonia is one of the most common causes of death among Alzheimer’s patients"
      ],
      "direct_transition": "PneumoniaEncounter",
      "assign_to_attribute": "hospice_reason",
      "target_encounter": "PneumoniaEncounter"
    },
    "PneumoniaEncounter": {
      "type": "Encounter",
      "encounter_class": "emergency",
      "reason": "Pneumonia",
      "codes": [
        {
          "system": "SNOMED-CT",
          "code": "4525004",
          "display": "Emergency department patient visit (procedure)"
        }
      ],
      "direct_transition": "Emergency Time"
    },
    "PneumoniaDeath": {
      "type": "Death",
      "range": {
        "low": 4,
        "high": 14,
        "unit": "days"
      },
      "condition_onset": "Pneumonia",
      "direct_transition": "Admit to Hospice"
    },
    "Death": {
      "type": "Death",
      "referenced_by_attribute": "Type of Alzheimer's",
      "direct_transition": "Terminal"
    },
    "Terminal": {
      "type": "Terminal"
    },
    "End_FirstObservations_Encounter": {
      "type": "EncounterEnd",
      "direct_transition": "ModerateDecline"
    },
    "Eventual_Hospice_Reason": {
      "type": "SetAttribute",
      "attribute": "hospice_reason",
      "direct_transition": "MCI_conversion",
      "value_attribute": "Type of Alzheimer's"
    },
    
   "MCI_conversion": {
    "type": "Simple", 
    "distributed_transition": [
	{"distribution": 0.30, "transition": "FirstObservations_Encounter"},
	{"distribution": 0.70, "transition": "MCI_Encounter"}
	],
	"remarks": [
        "Conversion Rate to AD is 30 % [Schmidtke, K., & Hermeneit, S. (2007). High rate of conversion to Alzheimer’s disease in a cohort of amnestic MCI patients. International Psychogeriatrics, 20(1), 96–108. https://doi.org/10.1017/S1041610207005509]"
      ]
  },
  
  "MCI_Encounter": {
      "type": "Encounter",
      "encounter_class": "ambulatory",
      "direct_transition": "MCI_Onset",
      "codes": [
        { "system": "SNOMED-CT", "code": "281036007", "display": "MCI" }
      ],
      "reason": "Type of Alzheimer's"
    },
    
    "MCI_Onset": {
    "type": "ConditionOnset",
    "assign_to_attribute": "Type of Alzheimer's",
    "codes": [
     { "system": "SNOMED-CT", "code": "429998004", "display": "MCI Stable" }
   ],
    "direct_transition": "Lab_analysis_MCI"
 },
  
  
  "Lab_analysis_MCI": {
      "type": "CallSubmodule",
      "submodule": "dementia/AD_lab_work_t1_v1",
      "direct_transition": "Diagnosis_CDR_SB_MCI"
    },
    "Diagnosis_CDR_SB_MCI": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 0.5, "high": 9 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the CDR-SB scale found here: Clinical Dementia Rating – Sum of Boxes (CDR-SB). A clinical endpoint to measure cognitive changes in the early stages of Alzheimer’s disease"
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR-SB" }
      ],
      "direct_transition": "Diagnosis_NPI_MCI"
    },
    "Diagnosis_NPI_MCI": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 0, "high": 25 },
      "unit": "{score}",
      "remarks": [
        "Thresholds for the NPI scale are calculated based on this equation: MMSE = 27.98 − 0.290 × NPI_Total_Score. Reference: 'Association Between Neuropsychiatric Symptom Trajectory and Conversion to Alzheimer Disease'. Tsz Wai Bentley Lo et al. (2020).For the Alzheimer’s Disease Neuroimaging Initiative"
      ],
      "codes": [
        { "system": "LOINC", "code": "72509-6", "display": "NPI" }
      ],
      "direct_transition": "Diagnosis_ADAS_Cog_11_MCI"
    },
   
     "Diagnosis_ADAS_Cog_11_MCI": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 1, "high": 20 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "54804-0", "display": "ADAS-Cog-11" }
      ],
      "direct_transition": "Diagnosis_ADCS_ADL_MCI"
    },
     "Diagnosis_ADCS_ADL_MCI": {
      "type": "Observation",
      "category": "survey",
      "range": { "low": 0, "high": 20 },
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "57048-1", "display": "ADCS-ADL" }
      ],
      "direct_transition": "Diagnosis_CDR_MCI"
    },
     "Diagnosis_CDR_MCI": {
      "type": "Observation",
      "category": "survey",
      "exact": {"quantity": 0.5},
      "unit": "{score}",
      "remarks": [
        
      ],
      "codes": [
        { "system": "LOINC", "code": "72088-8", "display": "CDR" }
      ],
      "direct_transition": "Diagnosis_CSF_AB42_MCI"
    },
    
    
      "Diagnosis_CSF_AB42_MCI": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 500, "high": 1000 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "33203-1", "display": "CSF-Aβ42" }
       ],
       "direct_transition": "Diagnosis_CSF_Ttau_MCI"
    },
    
     "Diagnosis_CSF_Ttau_MCI": {
       "type": "Observation",
       "category": "imaging",
       "range": { "low": 200, "high": 600 },
       "unit": "pg/ml",
       "remarks": [

       ],
       "codes": [
        { "system": "LOINC", "code": "58463-1", "display": "CSF-TAU" }
       ],
       "direct_transition": "Diagnosis_MMSE_Score_MCI"
    },
       
    
   "Diagnosis_MMSE_Score_MCI": {
     "type": "Observation",
     "category": "survey",
     "range": { "low": 18, "high": 28 },
     "unit": "{score}",
     "codes": [
      { "system": "LOINC", "code": "72106-8", "display": "MMSE" }
      ],
     "direct_transition": "FirstPrescription_MCI"
   },
   
   "FirstPrescription_MCI": {
      "type": "MedicationOrder",
      "assign_to_attribute": "Alzheimer's Medication",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "310436",
          "display": "Galantamine 4 MG Oral Tablet"
        }
      ],
      "direct_transition": "FirstPrescription_MCI2"
    },
    
   
    "FirstPrescription_MCI2": {
      "type": "MedicationOrder",
      "assign_to_attribute": "Alzheimer's Medication",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "997223",
          "display": "Donepezil hydrochloride 10 MG Oral Tablet"
        }
      ],
      "direct_transition": "FirstPrescription_MCI3"
    },
    
    
    "FirstPrescription_MCI3": {
      "type": "MedicationOrder",
      "assign_to_attribute": "Alzheimer's Medication",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "313185",
          "display": "Tacrine 10 MG Oral Capsule"
        }
      ],
      "direct_transition": "FirstPrescription_MCI4"
    },
    
   
     "FirstPrescription_MCI4": {
      "type": "MedicationOrder",
      "assign_to_attribute": "Alzheimer's Medication",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "2608323",
          "display": "Lecanemab 10 MG/Kg Injection"
        }
      ],
      "direct_transition": "SecondPrescription_MCI"
    },
    
     "SecondPrescription_MCI": {
      "type": "MedicationOrder",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "996740",
          "display": "Memantine hydrochloride 2 MG/ML Oral Solution"
        }
      ],
      "direct_transition": "FirstPrescription_MCI5"
    },
    
  
     "FirstPrescription_MCI5": {
      "type": "MedicationOrder",
      "assign_to_attribute": "Alzheimer's Medication",
      "reason": "Type of Alzheimer's",
      "codes": [
        {
          "system": "RxNorm",
          "code": "2608324",
          "display": "Rivastigmina 1,5 MG oral"
        }
      ],
      "direct_transition": "MildDecline"
    },
    
  

  "MildDecline": {
      "type": "Delay",
      "range": { "low": 2, "high": 3, "unit": "months" },
      "remarks": [
        "3. Mild decline, aka mild cognitive impairment (MCI) progresses to the next stage in generally 2-4 years",
        "Persons at this stage display subtle deficits which are noted by others close to the subject",
        "https://www.alzinfo.org/understand-alzheimers/clinical-stages-of-alzheimers/"
      ],
      "conditional_transition": [
        {
          "condition": { "condition_type": "Age", "operator": ">", "quantity": 80, "unit": "years" },
          "transition": "End_MCI_Encounter",
          "remarks": [
            "if the symptom is sufficiently noticeable enough people can be diagnosed in this stage, if not they will be diagnosed in the next stage"
          ]
        },
       
        { "transition": "Lab_analysis_MCI" }
      ]
    },
  
  "End_MCI_Encounter": {
      "type": "EncounterEnd",
      "direct_transition": "Death"
    },
  
  
  
  
    "Admit to Hospice": {
      "type": "SetAttribute",
      "attribute": "hospice",
      "direct_transition": "Terminal",
      "value": true
    },
    "Emergency Time": {
      "type": "Delay",
      "distribution": {
        "kind": "EXPONENTIAL",
        "parameters": {
          "mean": 3
        }
      },
      "unit": "hours",
      "direct_transition": "End Emergency Visit"
    },
    "End Emergency Visit": {
      "type": "EncounterEnd",
      "direct_transition": "PneumoniaDeath",
      "discharge_disposition": {
        "system": "NUBC",
        "code": 50,
        "display": "Discharged/transferred to Hospice - home"
      }
    }
  },
  "gmf_version": 1
}