Fig. 1.

High-level model diagram outlining the key relationships in AD ACE simulator. AD Alzheimer’s disease, DMT disease-modifying therapy, ADAS-Cog Alzheimer’s Disease Assessment Scale-Cognitive, ADL activities of daily living, ApoE4 apolipoprotein E4, ARIA-E amyloid-related imaging abnormalities-edema/effusion, CDRSB Clinical Dementia Rating Sum of Boxes, CSF t-tau cerebrospinal fluid total tau, DAD Disability Assessment Scale for Dementia, DS dependence scale, FDG-PET fluorodeoxyglucose–positron emission tomography, IADL instrumental activities of daily living, MMSE Mini-Mental State Examination, NPI Neuropsychiatric Inventory Questionnaire, PET positron emission tomography, SUVr standard uptake value ratio. ^*Key baseline patient characteristics: age, sex, race, education, ApoE4 status, baseline biomarkers, baseline scales. ^†DMT effect is directly applied on amyloid PET SUVr level. ^‡Includes ARIA-E. ^§DMT is initiated in patients with confirmed amyloid positive MCI due to AD or mild AD and discontinues once patients progress to moderate AD. ^¶Defined by CDRSB thresholds: MCI due to AD < 4.5, mild AD ≥ 4.5 to < 9.5, mild AD ≥ 9.5 to < 16, severe AD ≥ 16