Journal
NEUROLOGY
Volume 93, Issue 8, Pages E778-E790Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000007967
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Funding
- National Institute on Aging/NIH [P50 AG05131, U19 AG010483, P50 AG005131, U01 AG016976]
- Helen A. Jarret Chair for Alzheimer's Disease Research [P50 AG05131, R01 AG049810]
- National Institute on Aging [P50 AG005131, P30 AG019610, P30 AG013846, P50 AG008702, P50 AG025688, P50 AG047266, P30 AG010133, P50 AG005146, P50 AG005134, P50 AG016574, P50 AG005138, P30 AG008051, P30 AG013854, P30 AG008017, P30 AG010161, P50 AG047366, P30 AG010129, P50 AG016573]
- NIA [P50 AG023501, P30 AG035982, P30 AG028383, P30 AG053760, P30 AG010124, P50 AG005133, P50 AG005142, P30 AG012300, P30 AG049638, P50 AG005136, P50 AG033514, P50 AG005681, P50 AG047270]
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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 Alzheimer's 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 epsilon 4, 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.
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