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

Alzheimers Dement. 2023 Jan 17. doi: 10.1002/alz.12922. Online ahead of print.


Introduction: The relationship between initial cognitive symptoms and subsequent rate of clinical decline is important in clinical care and the design of dementia clinical trials.

Methods: 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. Linear mixed models evaluated the longitudinal outcome of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score.

Results: 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.

Discussion: Initial cognitive symptoms, despite varied underlying pathology, are a predictor of longitudinal functional outcomes among dementias.

Highlights: 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.

Keywords: Alzheimer's; Lewy body; cognitive decline; initial cognitive symptom; mixed dementia; neuropathology; rate of progression.