Initial non-amnestic symptoms relate to faster rate of functional and cognitive decline compared to amnestic symptoms in neuropathologically confirmed dementias.

Abstract

The relationship between initial cognitive symptoms and subsequent rate of clinical decline is important in clinical care and the design of dementia clinical trials. This retrospective longitudinal, autopsy-confirmed, cohort study among 2426 participants in the National Alzheimer's Coordinating Center database included Alzheimer's disease (AD) pathology, n=1187; Lewy body pathology (LBP), n=331; and mixed pathology (AD-LBP), n=904. The predominant initial cognitive symptom was assessed clinically. Linearmixed modelsevaluated the longitudinal outcome of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. Non-amnestic initial symptoms had a faster rate of decline than amnestic symptoms in all three groups. Language symptoms had a faster rate of decline in all three groups. Executive symptoms had a faster rate of decline than amnestic in AD and AD-LBP. There was a similar trend for visuospatial symptoms in AD-LBP. Initial cognitive symptoms, despite varied underlying pathology, are a predictor of longitudinal functional outcomes among dementias. Initial non-amnestic symptoms had a faster rate of longitudinal cognitive and functional decline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores than amnestic symptoms among Alzheimer's disease, Lewy body pathology, and mixed neuropathology. Given the relative size of CDR-SB changes in Alzheimer's disease clinical trials, clarifying the nature of initial symptoms could be an important variable in ensuring appropriately designed clinical trials.