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O4‐02‐02: Pathologies underlying longitudinal cognitive decline in old age
Author(s) -
Erten-Lyons Deniz,
Mattek Nora,
Dodge Hiroko H.,
Woltjer Randy,
Howieson Diane,
Silbert Lisa C.,
Piccinin Andrea,
Hofer Scott,
Kaye Jeffrey
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.07.352
Subject(s) - cognitive decline , hippocampal sclerosis , dementia , neuropathology , psychology , neuropsychology , cognition , medicine , episodic memory , pathological , neuroscience , gerontology , disease , temporal lobe , epilepsy
Objective: This study examines the association between trajectories of memory and executive function decline and brain pathologies. Background: Contributions of different brain pathologies to domain-specific cognitive trajectories is not well studied. Methods: Two-hundred-twenty-seven Oregon Alzheimers Disease Center research participants who were cognitively intact at entry were followed on average for 7.3 years with annual neuropsychological testing until death and autopsy. Last evaluation was on average 8.4 months prior to death. Mean age at death was 93.8 years. Mixed-effects models examined the relationship between longitudinal decline in memory and executive function and pathology (neurofibrillary tangles (NFTs), neuritic plaques (NPs), gross infarcts, hippocampal sclerosis, and, Lewy bodies) and APOE genotype, adjusting for duration of follow up, age at death and years of education. In secondary models diagnosis was added as a time varying covariate to the main models. Results: Memory decline over time was associated with presence of hippocampal sclerosis (p=0.01), Braak score 5 or 6 (p=0.003) and the e4 allele (p=0.007). Executive function decline over time was associated with presence of gross infarcts (p=0.005), and hippocampal sclerosis (p=0.05). Diagnosis of MCI or dementia, as a time-varying covariate, was associated with steeper declines in memory and executive function independent of pathological measures (p<. 0001). Conclusions: Memory decline was most strongly associated with NFT burden, and executive function decline with cerebrovascular disease. Presence of the e4 allele was associated with memory decline independent of pathologies, suggesting that APOE may be involved in mechanisms beyond those related to amyloid metabolism. Disclosure: Dr. Nguyen has nothing to disclose. Dr. Mattek has nothing to disclose. Dr. Dodge has nothing to disclose. Dr. Woltjer has nothing to disclose. Dr. Howieson has nothing to disclose. Dr. Silbert has nothing to disclose. Dr. Hofer has nothing to disclose. Dr. Kaye has received personal compensation for activities with Eli Lilly & Co. Dr. Piccinin has nothing to disclose. Dr. Erten-Lyons has received research support from Lundbeck, Eisai, Roche and Lilly.