2025 American Academy of Neurology Abstract Website

Objective:

To assess the longitudinal rate of cognitive trajectory in Alzheimer’s disease and clinical mimics.

Background:

Neuropathology at autopsy remains the standard for a final diagnosis of Alzheimer’s disease(AD) while other types of dementia(AD-mimics) confound the accuracy of a clinical diagnosis. Evidence suggests that those with a concordant diagnosis(AD-AD) perform significantly worse on neuropsychological inventories than AD-mimics at baseline and last visit.

Design/Methods:

De-identified information from the National Alzheimer’s Coordinating Center(NACC) was retrospectively reviewed to include participants with a clinical AD diagnosis at their last visit. Participants with moderate to frequent neuritic plaques and a Braak stage between III-VI were categorized as AD-AD under a modified version of the National Institute on Aging’s neuropathological change guidelines. Otherwise, they were AD-mimics, which may include but are not limited to Lewy bodies disease, frontotemporal dementia, vascular dementia, and hippocampal sclerosis. Statistical analyses were conducted on demographics and 14 neuropsychological batteries assessing attention, dementia severity, executive function, language, memory, processing speed, and visuospatial ability.

Results:

As of the December 2023 data freeze, 3013 participants met initial criteria and had neuropathology data available, of which 2351(78.03%) were AD-AD. AD-mimics were older at death(mean 82.14±9.82 vs. 88.51±8.32, p<0.001), less impaired on CDR at last visit(mean 12.64±5.36 vs. 8.73±6.15, p<0.001), and have a lower prevalence of APOEɛ4 alleles(60.12% vs. 30.37%, p<0.001). Further, AD-mimics had significantly higher neuropsychological scores at baseline except for visuospatial ability(p=0.65) and slower rates of decline(p<0.001) across all domains after adjusting for age at each visit, sex, and education level.

Conclusions:

This review of clinical and autopsy data from NACC showed that AD-mimics represent 21.97% of clinical AD diagnoses and had better cognitive performance at baseline with a slower progression of decline compared to the AD-AD group. These findings contribute to the expanding knowledge base for distinguishing AD from other dementia subtypes, facilitating timely diagnosis and adequate care.