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Dissociable effects of APOE-ε4 and β-amyloid pathology on visual working memory.

ABSTRACT: Although APOE-ε4 carriers are at significantly higher risk of developing Alzheimer's disease than non-carriers¹, controversial evidence suggests that APOE-ε4 might confer some advantages, explaining the survival of this gene (antagonistic pleiotropy)^2,3. In a population-based cohort born in one week in 1946 (assessed aged 69-71), we assessed differential effects of APOE-ε4 and β-amyloid pathology (quantified using ¹⁸F-Florbetapir-PET) on visual working memory (object-location binding). In 398 cognitively normal participants, APOE-ε4 and β-amyloid had opposing effects on object identification, predicting better and poorer recall respectively. ε4-carriers also recalled locations more precisely, with a greater advantage at higher β-amyloid burden. These results provide evidence of superior visual working memory in ε4-carriers, showing that some benefits of this genotype are demonstrable in older age, even in the preclinical stages of Alzheimer's disease.

SUBMITTER: Lu K

PROVIDER: S-EPMC7612005 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Dissociable effects of APOE-ε4 and β-amyloid pathology on visual working memory.

Lu Kirsty K Nicholas Jennifer M JM Pertzov Yoni Y Grogan John J Husain Masud M Pavisic Ivanna M IM James Sarah-Naomi SN Parker Thomas D TD Lane Christopher A CA Keshavan Ashvini A Keuss Sarah E SE Buchanan Sarah M SM Murray-Smith Heidi H Cash David M DM Malone Ian B IB Sudre Carole H CH Coath William W Wong Andrew A Henley Susie M D SMD Fox Nick C NC Richards Marcus M Schott Jonathan M JM Crutch Sebastian J SJ

Nature aging 20211007 11

Although APOE-ε4 carriers are at significantly higher risk of developing Alzheimer's disease than non-carriers1, controversial evidence suggests that APOE-ε4 might confer some advantages, explaining the survival of this gene (antagonistic pleiotropy)2,3. In a population-based cohort born in one week in 1946 (assessed aged 69-71), we assessed differential effects of APOE-ε4 and β-amyloid pathology (quantified using 18F-Florbetapir-PET) on visu ...[more]

PMID: 34806027

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Project description:ImportanceTypical cognitive aging may be defined as age-associated changes in cognitive performance in individuals who remain free of dementia. Ideally, the full adult age spectrum should be included to assess brain imaging findings associated with typical aging.ObjectiveTo compare age, sex, and APOE ε4 effects on memory, brain structure (adjusted hippocampal volume [HVa]), and amyloid positron emission tomography (PET) in cognitively normal individuals aged 30 to 95 years old.Design, setting, and participantsCross-sectional observational study (March 2006 to October 2014) at an academic medical center. We studied 1246 cognitively normal individuals, including 1209 participants aged 50 to 95 years old enrolled in a population-based study of cognitive aging and 37 self-selected volunteers aged 30 to 49 years old.Main outcomes and measuresMemory, HVa, and amyloid PET.ResultsOverall, memory worsened from age 30 years through the 90s. The HVa worsened gradually from age 30 years to the mid-60s and more steeply beyond that age. The median amyloid PET was low until age 70 years and increased thereafter. Memory was worse in men than in women overall (P < .001) and more specifically beyond age 40 years. The HVa was lower in men than in women overall (P < .001) and more specifically beyond age 60 years. There was no sex difference in amyloid PET at any age. Within each sex, memory performance and HVa were not different by APOE ε4 status at any age. From age 70 years onward, APOE ε4 carriers had significantly greater median amyloid PET than noncarriers. However, the ages at which 10% of the population were amyloid PET positive were 57 years for APOE ε4 carriers and 64 years for noncarriers.Conclusions and relevanceMale sex is associated with worse memory and HVa among cognitively normal individuals, while APOE ε4 is not. In contrast, APOE ε4 is associated with greater amyloid PET (from age 70 years onward), while sex is not. Worsening memory and HVa occur at earlier ages than abnormal amyloid PET. Therefore, neuropathological processes other than β-amyloidosis must underlie declines in brain structure and memory function in middle age. Our findings are consistent with a model of late-onset Alzheimer disease in which β-amyloidosis arises in later life on a background of preexisting structural and cognitive decline that is associated with aging and not with β-amyloid deposits.

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Dissociable effects of APOE-ε4 and β-amyloid pathology on visual working memory.

Publications

Dissociable effects of <i>APOE</i>-ε4 and β-amyloid pathology on visual working memory.

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Dataset Information

Dissociable effects of APOE-ε4 and β-amyloid pathology on visual working memory.

Publications

Dissociable effects of &lt;i&gt;APOE&lt;/i&gt;-ε4 and β-amyloid pathology on visual working memory.

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OmicsDI is part of the ELIXIR infrastructure

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Dissociable effects of <i>APOE</i>-ε4 and β-amyloid pathology on visual working memory.