Work

Cognitive heterogeneity in probable Alzheimer disease: Clinical and neuropathologic features

Year: 2019

Type: article

Abstract: Objective To identify heterogeneity in cognitive profiles of patients with probable Alzheimer disease (AD) who have mild to moderate dementia and satisfy inclusion and exclusion criteria for a typical AD clinical trial, and to determine whether cognitive profiles are systematically related to the clinical course and neuropathologic features of the disease. Methods Neuropsychological test data from patients with mild to moderate probable AD (n = 4,711) were obtained from the National Alzheimer9s Coordinating Center. Inclusion and exclusion criteria usually used in AD clinical trials were applied. Principal component analysis and model-based clustering were used to identify cognitive profiles in a subset of patients with autopsy-verified AD (n = 800) and validated in the overall (nonautopsy) sample and an independent cohort with similar test data. Relationships between cognitive profile, clinical characteristics, and rate of decline were examined with mixed-effects models. Results In the autopsy-confirmed sample, 79.6% of patients had a typical AD cognitive profile (greater impairment of episodic memory than other cognitive functions), and 20.4% had an atypical profile (comparable impairment across cognitive domains). Similar results were obtained in the overall (typical 79.8%, atypical 20.2%) and validation (typical 71.8%, atypical 28.2%) samples. Atypicality was associated with younger age, male sex, lower probability of APOE ε4, less severe global dementia, higher depression scores, lower Braak stage at autopsy, and slower cognitive decline. Conclusion We can reliably identify distinct cognitive profiles among patients with clinically diagnosed probable AD that are associated with tangle pathology and with different rates of decline. This may have implications for clinical trials in AD, especially therapies targeting tau.

Source: Neurology

DOI: 10.1212/wnl.0000000000007967

Authors: Yuqi Qiu, Diane M. Jacobs, Karen Messer, David P. Salmon, Howard H. Feldman

Institution: University of California San Diego

Language: English

Topic: Dementia and Cognitive Impairment Research

Subfield: Psychiatry and Mental health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute on Aging