Clinical Profiles of Arteriolosclerosis and Alzheimer Disease at Mild Cognitive Impairment and Mild Dementia in a National Neuropathology Cohort

Objective: We sought to evaluate early clinical differences between cerebral arteriolosclerosis (pARTE), Alzheimer disease (pAD), and AD with arteriolosclerosis (ADARTE). Methods: Using National Alzheimer's Coordinating Center neuropathology diagnoses, we defined pARTE (n=21), pAD (n=203), and ADARTE (n=158) groups. We compared demographics, medical history, psychometrics, neuropsychiatric symptoms, and apolipoprotein E (APOE) allele variants across neuropathology groups. Retrospective timepoints were first evaluation with Global Clinical Dementia Rating (CDR) score of 0.5 and 1.0, via the CDR Dementia Staging Instrument, corresponding to mild cognitive impairment (MCI) and mild dementia, respectively. Results: In MCI, clinical differences were minimal but pARTE subjects were older, had later onset cognitive decline, and progressed less severely than pAD. In mild dementia, pAD subjects were younger and had earlier onset of decline. Neuropsychiatric (depression) and psychometric (Logical Memory Delayed Recall, Trails B) differences also emerged between the groups. In MCI, APOE4 associated with worse Logical Memory Delayed Recall in pAD and ADARTE. In mild dementia, APOE4 associated with better animal fluency in pAD, but with better Trails A performance and more neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire) in ADARTE. Conclusions: Differences between pARTE, pAD, and ADARTE emerge at mild dementia rather than MCI. APOE4 has varied cognitive and psychiatric impact dependent on neuropathology group and stage.