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Sex differences in the association between AD biomarkers and cognitive decline.

ABSTRACT: Women are disproportionately affected by Alzheimer's disease (AD) in terms of both disease prevalence and severity. Previous autopsy work has suggested that, in the presence of AD neuropathology, females are more susceptible to the clinical manifestation of AD. This manuscript extends that work by evaluating whether sex alters the established associations between cerebrospinal fluid (CSF) biomarker levels and brain aging outcomes (hippocampal volume, cognition). Participants were drawn from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and included individuals with normal cognition (n = 348), mild cognitive impairment (n = 565), and AD (n = 185). We leveraged mixed effects regression models to assess the interaction between sex and baseline cerebrospinal fluid biomarker levels of amyloid-?42 (A?-42) and total tau on cross-sectional and longitudinal brain aging outcomes. We found a significant interaction between sex and A?-42 on longitudinal hippocampal atrophy (p = 0.002), and longitudinal decline in memory (p = 0.017) and executive function (p = 0.025). Similarly, we observed an interaction between sex and total tau level on longitudinal hippocampal atrophy (p = 0.008), and longitudinal decline in executive function (p = 0.034). Women with A?-42 and total tau levels indicative of worse pathological changes showed more rapid hippocampal atrophy and cognitive decline. The sex difference was particularly pronounced among individuals with MCI, with lower education, and varied by APOE ?4 allele. These results suggest females may be more susceptible to the clinical manifestation of AD.

SUBMITTER: Koran MEI

PROVIDER: S-EPMC4972701 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Sex differences in the association between AD biomarkers and cognitive decline.

Koran Mary Ellen I MEI Wagener Madison M Hohman Timothy J TJ

Brain imaging and behavior 20170201 1

Women are disproportionately affected by Alzheimer's disease (AD) in terms of both disease prevalence and severity. Previous autopsy work has suggested that, in the presence of AD neuropathology, females are more susceptible to the clinical manifestation of AD. This manuscript extends that work by evaluating whether sex alters the established associations between cerebrospinal fluid (CSF) biomarker levels and brain aging outcomes (hippocampal volume, cognition). Participants were drawn from the ...[more]

PMID: 26843008

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Project description:ImportanceSex differences in dementia risk are unclear, but some studies have found greater risk for women.ObjectiveTo determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk.Design, setting, and participantsThis cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020.ExposureSex.Main outcomes and measuresThe primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition.ResultsAmong 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95% CI, -0.08 to -0.05 points/y; P < .001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P < .001). Men and women had similar declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P = .61).Conclusions and relevanceThe results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.

Project description:ImportanceAn association between sleep duration and the trajectory of cognitive decline has not been conclusively demonstrated.ObjectiveTo investigate the association between sleep duration and cognitive decline by a pooled analysis of 2 nationally representative aging cohorts.Design, setting, and participantsA pooled cohort study using data from waves 4 to 8 (2008-2009 to 2016-2017) in the English Longitudinal Study of Ageing and waves 1 to 3 (2011 to 2015) in the China Health and Retirement Longitudinal Study in a population-based setting. Participants were 2 randomly enrolled cohorts comprising 28 756 individuals living in England who were 50 years or older and those living in China who were 45 years or older.ExposureSelf-reported sleep duration per night according to face-to-face interviews.Main outcomes and measuresGlobal cognitive z scores were calculated according to immediate and delayed recall test, an animal fluency test, the serial sevens test, an intersecting pentagon copying test, and a date orientation test.ResultsData were analyzed from 20 065 participants, including 9254 from the English Longitudinal Study of Ageing (mean [SD] age, 64.6 [9.8] years; 55.9% [5174 of 9254] women; median follow-up duration, 8 [interquartile range, 6-8] years) and 10 811 from the China Health and Retirement Longitudinal Study (mean [SD] age, 57.8 [9.0] years; 50.2% [5425 of 10 811] men; median follow-up duration, 4 [interquartile range, 4-4] years). During 100 000 person-years of follow-up, global cognitive z scores in individuals with 4 hours or less (pooled β = -0.022; 95% CI, -0.035 to -0.009 SD per year; P = .001) and 10 hours or more (pooled β = -0.033; 95% CI, -0.054 to -0.011 SD per year; P = .003) of sleep per night declined faster than in the reference group (7 hours per night) after adjusting for a number of covariates. An inverted U-shaped association between sleep duration and global cognitive decline was also observed.Conclusions and relevanceIn this pooled cohort study, an inverted U-shaped association between sleep duration and global cognitive decline was found, indicating that cognitive function should be monitored in individuals with insufficient (≤4 hours per night) or excessive (≥10 hours per night) sleep duration. Future studies are needed to examine the mechanisms of the association between sleep duration and cognitive decline.

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Sex differences in the association between AD biomarkers and cognitive decline.

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Sex differences in the association between AD biomarkers and cognitive decline.

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