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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:Importance:An association between sleep duration and the trajectory of cognitive decline has not been conclusively demonstrated. Objective:To investigate the association between sleep duration and cognitive decline by a pooled analysis of 2 nationally representative aging cohorts. Design, Setting, and Participants:A 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. Exposure:Self-reported sleep duration per night according to face-to-face interviews. Main Outcomes and Measures:Global 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. Results:Data 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 ??=?-0.022; 95% CI, -0.035 to -0.009 SD per year; P?=?.001) and 10 hours or more (pooled ??=?-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 Relevance:In 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.

Project description:ObjectiveThe goal of this study was to examine sex differences in tau distribution across the brain of older adults, using positron emission tomography (PET), and investigate how these differences might associate with cognitive trajectories.MethodsParticipants were 343 clinically normal individuals (women, 58%; 73.8 [8.5] years) and 55 individuals with mild cognitive impairment (MCI; women, 38%; 76.9 [7.3] years) from the Harvard Aging Brain Study and the Alzheimer's Disease Neuroimaging Initiative. We examined 18 F-Flortaucipir (FTP)-positron emission tomography (PET) signal across 41 cortical and subcortical regions of interest (ROIs). Linear regression models estimated the effect of sex on FTP-signal for each ROI after adjusting for age and cohort. We also examined interactions between sex*Aβ-PET positive / negative (+ / -) and sex*apolipoprotein ε4 (APOEε4) status. Linear mixed models estimated the moderating effect of sex on the relationship between a composite of sex-differentiated tau ROIs and cognitive decline.ResultsWomen showed significantly higher FTP-signals than men across multiple regions of the cortical mantle (p < 0.007). β-amyloid (Aβ)-moderated sex differences in tau signal were localized to medial and inferio-lateral temporal regions (p < 0.007); Aβ + women exhibited greater FTP-signal than other groups. APOEε4-moderated sex differences in FTP-signal were only found in the lateral occipital lobe. Women with higher FTP-signals in composite ROI exhibited faster cognitive decline than men (p = 0.04).InterpretationTau vulnerability in women is not just limited to the medial temporal lobe and significantly contributed to greater risk of faster cognitive decline. Interactive effects of sex and Aβ were predominantly localized in the temporal lobe, however, sex differences in extra-temporal tau highlights the possibility of accelerated tau proliferation in women with the onset of clinical symptomatology. ANN NEUROL 2020;88:921-932.

Project description:We aimed to detect the possible accelerating role of previous traumatic brain injury (TBI) exposures on the onset of later cognitive decline assessed across different brain diseases. We analyzed data from the National Alzheimer's Coordinating Center (NACC), which provide information on history of TBI and longitudinal data on cognitive and non-cognitive domains for each available subject. At the time of this investigation, a total of 609 NACC subjects resulted to have a documented history of TBI. We compared subjects with and without a history of previous TBI (of any type) at the time of their first cognitive decline assessment, and termed them, respectively, TBI+ and TBI- subjects. Three hundred and sixty-one TBI+ subjects (229 male/132 female) and 248 TBI- subjects (156 male/92 female) were available. The analyses included TBI+ and TBI- subjects with a clinical diagnosis of Mild Cognitive Impairment, Alzheimer's disease, Dementia with Lewy bodies, Progressive supranuclear palsy, Corticobasal degeneration, Frontotemporal dementia, Vascular dementia, non-AD Impairment, and Parkinson's disease. The data showed that the mean age of TBI+ subjects was lower than TBI- subjects at the time of their first cognitive decline assessment (71.6 ± 11.2 vs. 74.8 ± 9.5 year; p < 0.001). Moreover, the earlier onset of cognitive decline in TBI+ vs. TBI- subjects was independent of sex, race, attained education, APOE genotype, and importantly, clinical diagnoses. As for specific cognitive aspects, MMSE, Trail Making Test part B and WAIS-R scores did not differ between TBI+ and TBI- subjects, whereas Trail Making Test part A (p = 0.013) and Boston Naming test (p = 0.008) did. In addition, data showed that neuropsychiatric symptoms [based on Neuropsychiatry Inventory (NPI)] were much more frequent in TBI+ vs. TBI- subjects, including AD and non-AD neurodegenerative conditions such as PD. These cross-sectional analyses outcomes from longitudinally-assessed cohorts of TBI+ subjects that is, subjects with TBI exposure before the onset of cognitive decline in the contest of different neurodegenerative disorders and associated pathogenetic mechanisms, are novel, and indicate that a previous TBI exposure may act as a significant "age-lowering" factor on the onset of cognitive decline in either AD and non-AD conditions independently of demographic factors, education, APOE genotype, and current or upcoming clinical conditions.

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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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