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Association between APOE‐ε4 allele and CSF amyloid in memory performance differ by sex
Author(s) -
BrugulatSerrat Anna,
Tsoy Elena,
MilàAlomà Marta,
SánchezBenavides Gonzalo,
Buckley Rachel F.,
Gispert Juan Domingo,
Molinuevo Jose,
Possin Kate L,
Kramer Joel H
Publication year - 2021
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 - 10.1002/alz.055181
Subject(s) - apolipoprotein e , cognition , episodic memory , medicine , cohort , psychology , effects of sleep deprivation on cognitive performance , neuropsychology , association (psychology) , oncology , memory clinic , dementia , audiology , disease , psychiatry , psychotherapist
Background There is growing evidence of sex differences in the association between Alzheimer’s disease (AD) biomarkers and cognition. However, few studies have examined the effect of sex on the associations between established AD risk factors and cognitive performance in clinically normal older adults. This study aimed to elucidate potential sex differences in the relationship between APOE‐ε4 status, AD biomarkers, and cognitive performance in a large multinational cohort of clinically normal older adults. Method Participants were 952 cognitively unimpaired older adults from the multicenter European Prevention of Alzheimer’s Disease (EPAD) study (age range 50‐88 years, mean age 65.0(7.0), mean education 14.6(3.6) years, 58% females). All participants underwent a lumbar puncture and CSF Aβ42, p‐tau and t‐tau biomarkers (Roche Elecsys®) were measured, APOE genotyping, and a battery of digital cognitive tests (UCSF TabCAT; Favorites (associative memory), Dot Counting (executive function), and Flanker (processing speed)). APOE genotype was dichotomized (ε4 carrier vs. ε4 non‐carrier). We performed multiple linear regression models to examine the effect of sex, CSF biomarkers, APOE‐ε4 , and their interactions on cognitive performance covarying for age, education, and testing language. Result There were no differences in age (p=.07), frequency of APOE‐ε4 carriers (33.1%, p=.55) or CSF biomarkers (all p>0.1) between males and females. Females had lower educational attainment (p=.01). Females outperformed males on an associative memory task (p=.002), whereas males performed better on tasks of working memory (p=.01) and inhibitory control (p=.01). A sex*Aβ* APOE‐ε4 status interaction (p=.01) revealed APOE‐ε4 carriership and abnormal levels of CSF Aβ were associated with poorer associative memory performance only in males (Fig 1). Conclusion Sex seems to moderate the association between CSF Aβ and APOE‐ε4 allele and memory performance in cognitively unimpaired older adults. Our results suggest a cross‐sectional association of APOE‐ε4 and CSF Aβ with cognitive performance in males that complement previous literature on the relationship between APOE ‐ε4 and longitudinal cognitive decline in females. Taken together, these findings highlight the importance of understanding the complexity of sex differences in individuals at higher risk of AD.