Longitudinal cognitive performance of Alzheimer's disease neuropathological subtypes. Issue 1 (27th September 2021)

• Record Type: Journal Article
• Authors: Uretsky, Madeline; Gibbons, Laura E.; Mukherjee, Shubhabrata; Trittschuh, Emily H.; Fardo, David W.; Boyle, Patricia A.; Keene, C. Dirk; Saykin, Andrew J.; Crane, Paul K.; Schneider, Julie A.; Mez, Jesse
• Is Part Of: Alzheimer's & dementia. Volume 7:Issue 1(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-27
• Subjects: Alzheimer's disease -- cognitive decline -- cognitive trajectories -- executive function -- hippocampal sparing -- language -- limbic predominant -- memory -- Memory and Aging Project -- neuropathological subtypes -- Religious Orders Study -- visuospatial function; Dementia -- Periodicals; Dementia -- Treatment -- Periodicals; Alzheimer's disease -- Treatment -- Periodicals; Alzheimer's disease -- Periodicals; 616.831
• DOI: 10.1002/trc2.12201
• Languages: English
• ISSNs: 2352-8737

Abstract

Abstract: Introduction: Alzheimer's disease (AD) neuropathological subtypes (limbic predominant [lpAD], hippocampal sparing [HpSpAD], and typical [tAD]), defined by relative neurofibrillary tangle (NFT) burden in limbic and cortical regions, have not been studied in prospectively characterized epidemiological cohorts with robust cognitive assessments. Methods: Two hundred ninety‐two participants with neuropathologically confirmed AD from the Religious Orders Study and Memory and Aging Project were categorized by neuropathological subtype based on previously specified diagnostic criteria using quantitative regional NFT counts. Rates of cognitive decline were compared across subtypes using linear mixed‐effects models that included subtype, time, and a subtype–time interaction as predictors and four cognitive domain factor scores (memory, executive function, language, visuospatial) and a global score as outcomes. To assess if memory was relatively preserved in HpSpAD, non‐memory factor scores were included as covariates in the mixed‐effects model with memory as the outcome. Results: There were 57 (20%) with lpAD, 22 (8%) with HpSpAD and 213 (73%) with tAD. LpAD died significantly later than the participants with tAD (2.4 years, P = .01) and with HpSpAD (3.8 years, P = .03). Compared to tAD, HpSpAD, but not lpAD, performed significantly worse in all cognitive domains at the time of initial impairment and declined significantly faster in memory, language, and globally. HpSpAD did not have relatively preserved memory performance at any time point. Conclusion: The relative frequencies of AD neuropathological subtypes in an epidemiological sample were consistent with a previous report in a convenience sample. People with HpSpAD decline rapidly, but may not have a memory‐sparing clinical syndrome. Cohort‐specific differences in regional tau burden and comorbid neuropathology may explain the lack of clinicopathological correlation.