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Sex differences in brain aging and predictors of neurodegeneration in cognitively healthy older adults.

ABSTRACT: We evaluated sex differences in MRI-based volume loss and differences in predictors of this neurodegeneration in cognitively healthy older adults. Mixed-effects regression was used to compare regional brain volume trajectories of 295 male and 328 female cognitively healthy Baltimore Longitudinal Study of Aging participants, aged 55-92 years, with up to 20 years of follow-up and to assess sex differences in the associations of age, hypertension, obesity, APOE e4 carrier status, and high-density lipoprotein cholesterol with regional brain volume trajectories. For both sexes, older age was associated with steeper volumetric declines in many brain regions, with sex differences in volume loss observed in frontal, temporal, and parietal regions. In males, hypertension and higher high-density lipoprotein cholesterol were protective against volume loss in the hippocampus, entorhinal cortex, and parahippocampal gyrus. In females, hypertension was associated with steeper volumetric decline in gray matter, and obesity was protective against volume loss in temporal gray matter. Predictors of volume change may affect annual rates of volume change differently between men and women.

SUBMITTER: Armstrong NM

PROVIDER: S-EPMC9310670 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Sex differences in brain aging and predictors of neurodegeneration in cognitively healthy older adults.

Armstrong Nicole M NM An Yang Y Beason-Held Lori L Doshi Jimit J Erus Guray G Ferrucci Luigi L Davatzikos Christos C Resnick Susan M SM

Neurobiology of aging 20190605

We evaluated sex differences in MRI-based volume loss and differences in predictors of this neurodegeneration in cognitively healthy older adults. Mixed-effects regression was used to compare regional brain volume trajectories of 295 male and 328 female cognitively healthy Baltimore Longitudinal Study of Aging participants, aged 55-92 years, with up to 20 years of follow-up and to assess sex differences in the associations of age, hypertension, obesity, APOE e4 carrier status, and high-density l ...[more]

PMID: 31280118

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Project description:IntroductionLate onset Alzheimer's disease (AD) is the most common form of dementia, in which almost 70% of patients are women.HypothesisWe hypothesized that women show worse global FC metrics compared to men, and further hypothesized a sex-specific positive correlation between FC metrics and cognitive scores in women.MethodsWe studied cognitively healthy individuals from the Alzheimer's Disease Neuroimaging Initiative cohort, with resting-state functional Magnetic Resonance Imaging. Metrics derived from graph theoretical analysis and functional connectomics were used to assess the global/regional sex differences in terms of functional integration and segregation, considering the amyloid status and the contributions of APOE E4. Linear mixed effect models with covariates (education, handedness, presence of apolipoprotein [APOE] E4 and intra-subject effect) were utilized to evaluate sex differences. The associations of verbal learning and memory abilities with topological network properties were assessed.ResultWomen had a significantly lower magnitude of the global and regional functional network metrics compared to men. Exploratory association analysis showed that higher global clustering coefficient was associated with lower percent forgetting in women and worse cognitive scores in men.ConclusionWomen overall show lower magnitude on measures of resting state functional network topology and connectivity. This factor can play a role in their different vulnerability to AD.Significance statementTwo thirds of AD patients are women but the reasons for these sex difference are not well understood. When this late onset form dementia arises is too late to understand the potential causes of this sex disparities. Studies on cognitively healthy elderly population are a fundamental approach to explore in depth this different vulnerability to the most common form of dementia, currently affecting 6.2 million Americans aged 65 and older are, which means that >1 in 9 people (11.3%) 65 and older are affected by AD. Approaches such as resting-state functional network topology and connectivity may play a key role in understanding and elucidate sex-dependent differences relevant to late-onset dementia syndromes.

Project description:ImportanceOlder adults are increasingly prescribed medications that have adverse effects. Prior studies have found a higher risk of motor vehicle crashes to be associated with certain medication use.ObjectiveTo determine whether specific medication classes were associated with performance decline as assessed by a standardized road test in a community sample of cognitively healthy older adults, to evaluate additional associations of poor road test performance with comorbid medical conditions and demographic characteristics, and to test the hypothesis that specific medication classes (ie, antidepressants, benzodiazepines, sedatives or hypnotics, anticholinergics, antihistamines, and nonsteroidal anti-inflammatory drugs or acetaminophen) would be associated with an increase in risk of impaired driving performance over time.Design, setting, and participantsThis was a prospective cohort study of 198 cognitively healthy adults 65 years and older with a valid driver's license who were followed up annually, with rolling enrollment. Data were collected from participants in St Louis, Missouri, and neighboring Illinois who were enrolled in the Knight Alzheimer's Disease Research Center. Data were collected from August 28, 2012, to March 14, 2023, and analyzed from April 1 to 25, 2023. Participants with healthy cognition, defined as a Clinical Dementia Rating score of 0 at baseline and subsequent visits, who had available clinical, neuropsychological, road tests, and self-reported medication data were included.ExposurePotentially driver-impairing medication use.Main outcomes and measuresThe primary outcome measure was performance on the Washington University Road Test (pass or marginal/fail). Multivariable Cox proportional hazards models were used to evaluate associations between potentially driver-impairing medication use and road test performance.ResultsOf the 198 included adults (mean [SD] baseline age, 72.6 [4.6] years; 87 female [43.9%]), 70 (35%) received a marginal/fail rating on the road test over a mean (SD) follow-up of 5.70 (2.45) years. Any use of antidepressants (adjusted hazard ratio [aHR], 2.68; 95% CI, 1.69-4.71), serotonin and norepinephrine reuptake inhibitors (aHR, 2.68; 95% CI, 1.54-4.64), sedatives or hypnotics (aHR, 2.70; 95% CI, 1.40-5.19), or nonsteroidal anti-inflammatory drugs (aHR, 2.72; 95% CI, 1.31-5.63) was associated with an increase in risk of receiving a marginal/fail rating on the road test compared with control individuals. Conversely, participants taking lipid-lowering agents had a lower risk of receiving a marginal/fail rating compared to control individuals. There were no statistically significant associations found between anticholinergic or antihistamines and poor performance.Conclusions and relevanceIn this prospective cohort study, specific medication classes were associated with an increase in risk of poor road test performance over time. Clinicians should consider this information and counsel patients accordingly when prescribing these medications.

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Sex differences in brain aging and predictors of neurodegeneration in cognitively healthy older adults.

Publications

Sex differences in brain aging and predictors of neurodegeneration in cognitively healthy older adults.

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