Distinct Characteristics of Suspected Non-Alzheimer Pathophysiology in Relation to Cognitive Status and Cerebrovascular Burden.

Abstract

This study investigated the prevalence and clinical characteristics of suspected non-Alzheimer disease pathophysiology (SNAP) across varying cognitive statuses and cerebral small vessel disease (CSVD) burden. We included 1992 participants with cognitive status categorized as cognitively unimpaired, mild cognitive impairment, or dementia. β-amyloid (Aβ, A) positivity was assessed by Aβ PET, and neurodegeneration (N) positivity was determined through hippocampal volume. Participants were further divided by the presence or absence of severe CSVD. The clinical and imaging characteristics of A-N+ (SNAP) group were compared with those of the A-N- and A+N+ groups. SNAP participants were older and had more vascular risk factors compared with A-N- and A+N+ in the CSVD(-) cohort. SNAP and A+N+ showed similar cortical thinning. At the dementia stage, SNAP had a cognitive trajectory similar to A+N+ in the CSVD(-) cohort. However, SNAP exhibited less cognitive decline than A+N+ in the CSVD(+) cohort. SNAP is characterized by distinct clinical and imaging characteristics; however, it does not necessarily indicate a benign prognosis, particularly at the dementia stage. These findings highlight the need to assess SNAP in relation to the cognitive stage and CSVD presence to better understand its progression and guide interventions.