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Sex and APOE: A memory advantage in male APOE ?4 carriers in midlife.

ABSTRACT: Short-term memory in middle-aged individuals with different APOE alleles was examined using a recently developed task which is sensitive to medial temporal lobe (MTL) damage. Individuals (age-range: 40-51 years) with ?3/?3, ?3/?4 and ?4/?4 APOE genotypes (N = 60) performed a delayed estimation task with a sensitive continuous measure of report. The paradigm allowed us to measure memory for items and their locations, as well as maintenance of identity-location feature binding in memory. There was a significant gene-dosage dependent effect of the ?4 allele on performance: memory decay or forgetting was slower in ?4 carriers, as measured by localization error and after controlling for misbinding errors. Furthermore ?4 carriers made less misbinding errors. These findings were specific to male carriers only. Thus, male ?4 carriers are at a behavioral advantage in midlife on a sensitive task of short-term memory. The results would be consistent with an antagonistic pleiotropy hypothesis and hightight the interaction of gender on the influence of APOE in cognition.

SUBMITTER: Zokaei N

PROVIDER: S-EPMC5333781 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Sex and APOE: A memory advantage in male APOE ε4 carriers in midlife.

Zokaei Nahid N Giehl Kathrin K Sillence Annie A Neville Matt J MJ Karpe Fredrik F Nobre Anna C AC Husain Masud M

Cortex; a journal devoted to the study of the nervous system and behavior 20161224

Short-term memory in middle-aged individuals with different APOE alleles was examined using a recently developed task which is sensitive to medial temporal lobe (MTL) damage. Individuals (age-range: 40-51 years) with ε3/ε3, ε3/ε4 and ε4/ε4 APOE genotypes (N = 60) performed a delayed estimation task with a sensitive continuous measure of report. The paradigm allowed us to measure memory for items and their locations, as well as maintenance of identity-location feature binding in memory. There was ...[more]

PMID: 28086184

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Project description:OBJECTIVEFew have characterized cognitive changes with age as a function of menopausal stage relative to men, or sex differences in components of memory in early midlife. The study aim was to investigate variation in memory function in early midlife as a function of sex, sex steroid hormones, and reproductive status.METHODSA total of 212 men and women aged 45 to 55 were selected for this cross-sectional study from a prenatal cohort of pregnancies whose mothers were originally recruited in 1959 to 1966. They underwent clinical and cognitive testing and hormonal assessments of menopause status. Multivariate general linear models for multiple memory outcomes were used to test hypotheses controlling for potential confounders. Episodic memory, executive function, semantic processing, and estimated verbal intelligence were assessed. Associative memory and episodic verbal memory were assessed using Face-Name Associative Memory Exam (FNAME) and Selective Reminding Test (SRT), given increased sensitivity to detecting early cognitive decline. Impacts of sex and reproductive stage on performance were tested.RESULTSWomen outperformed men on all memory measures including FNAME (??=?-0.30, P < 0.0001) and SRT (??=?-0.29, P?<?0.0001). Furthermore, premenopausal and perimenopausal women outperformed postmenopausal women on FNAME (initial learning, ?= 0.32, P?=?0.01) and SRT (recall, ?= 2.39, P?=?0.02). Across all women, higher estradiol was associated with better SRT performance (recall, ??=?1.96, P?=?0.01) and marginally associated with FNAME (initial learning, ??=?0.19, P?=?0.06).CONCLUSIONSThis study demonstrated that, in early midlife, women outperformed age-matched men across all memory measures, but sex differences were attenuated for postmenopausal women. Initial learning and memory retrieval were particularly vulnerable, whereas memory consolidation and storage were preserved. Findings underscore the significance of the decline in ovarian estradiol production in midlife and its role in shaping memory function.

Project description:BackgroundSubjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment. It has been suggested that individuals with SCD exhibited brain structural alterations in widespread cortical thinning or gray matter loss in the medial temporal and frontotemporal regions. Apolipoprotein E (APOE) ε4 allele is thought to be a genetic marker associated with risk of SCD. Neuropsychiatric symptoms may provide insight in detecting higher-risk elders for early Alzheimer's disease as well. Therefore, we aim to explore the characteristics of brain morphology in SCD and to determine whether it is influenced by APOE ε4 as well as neuropsychiatric symptoms in SCD.MethodsA total of 138 cognitively normal older individuals from the SILCODE cohort underwent a clinical interview, neuropsychological assessments, a blood test, and MRI. A two-sample t-test was used to examine the cortex volume and bilateral cortical surface area alterations between SCD (n = 65) and controls (n = 73). A general linear model analysis was used to test for both main and interaction effects of clinical phenotype (SCD vs. controls) and APOE on global and regional cortex volume and bilateral cortical surface area and thickness. A multiple linear regression analysis was conducted to determine the effects of the APOE genotype on the relationships between morphometric features and neuropsychiatric symptoms in SCD.ResultsCompared with controls, individuals with SCD showed decreased total cortical volumes and cortical surface area. SCD APOE ε4 carriers showed additive reduction in the right cortical surface area. The evaluation scores of anxiety symptoms were negatively associated with the right cortical surface area in SCD APOE 4 non-carriers.ConclusionsIndividuals with SCD had an altered cortical surface area, and APOE genotype and anxiety symptoms are modified factors on the cortical surface area decrease in SCD.Trial registrationClinicalTrials.gov (Identifier: NCT03370744 ). Registered 15 March 2017.

Dataset Information

Sex and APOE: A memory advantage in male APOE ?4 carriers in midlife.

Publications

Sex and APOE: A memory advantage in male APOE ε4 carriers in midlife.

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