Dataset Information

Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline.

ABSTRACT:

Objective

Our aim was to test the association of vascular risk factor exposure in midlife with progression of MRI markers of brain aging and measures of cognitive decline.

Methods

A total of 1,352 participants without dementia from the prospective Framingham Offspring Cohort Study were examined. Multivariable linear and logistic regressions were implemented to study the association of midlife vascular risk factor exposure with longitudinal change in white matter hyperintensity volume (WMHV), total brain volume (TBV), temporal horn volume, logical memory delayed recall, visual reproductions delayed-recall (VR-d), and Trail-Making Test B-A (TrB-A) performance a decade later.

Results

Hypertension in midlife was associated with accelerated WMHV progression (p < 0.001) and worsening executive function (TrB-A score; p = 0.012). Midlife diabetes and smoking were associated with a more rapid increase in temporal horn volume, a surrogate marker of accelerated hippocampal atrophy (p = 0.017 and p = 0.008, respectively). Midlife smoking also predicted a more marked decrease in total brain volume (p = 0.025) and increased risk of extensive change in WMHV (odds ratio = 1.58 [95%confidence interval 1.07-2.33], p = 0.021). Obesity in midlife was associated with an increased risk of being in the top quartile of change in executive function (1.39 [1.02-1.88], p = 0.035) and increasing waist-to-hip ratio was associated with marked decline in TBV (10.81 [1.44-81.01], p = 0.021). Longitudinal changes in brain structure were significantly correlated with decline in memory and executive function.

Conclusions

Midlife hypertension, diabetes, smoking, and obesity were associated with an increased rate of progression of vascular brain injury, global and hippocampal atrophy, and decline in executive function a decade later.

SUBMITTER: Debette S

PROVIDER: S-EPMC3146307 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Publications

Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline.

Debette S S Seshadri S S Beiser A A Au R R Himali J J JJ Palumbo C C Wolf P A PA DeCarli C C

Neurology 20110801 5

<h4>Objective</h4>Our aim was to test the association of vascular risk factor exposure in midlife with progression of MRI markers of brain aging and measures of cognitive decline.<h4>Methods</h4>A total of 1,352 participants without dementia from the prospective Framingham Offspring Cohort Study were examined. Multivariable linear and logistic regressions were implemented to study the association of midlife vascular risk factor exposure with longitudinal change in white matter hyperintensity vol ...[more]

PMID: 21810696

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Project description:BackgroundType 2 diabetes mellitus (T2DM) is known to be associated with neurobiological and cognitive deficits; however, their extent, overlap with aging effects, and the effectiveness of existing treatments in the context of the brain are currently unknown.MethodsWe characterized neurocognitive effects independently associated with T2DM and age in a large cohort of human subjects from the UK Biobank with cross-sectional neuroimaging and cognitive data. We then proceeded to evaluate the extent of overlap between the effects related to T2DM and age by applying correlation measures to the separately characterized neurocognitive changes. Our findings were complemented by meta-analyses of published reports with cognitive or neuroimaging measures for T2DM and healthy controls (HCs). We also evaluated in a cohort of T2DM-diagnosed individuals using UK Biobank how disease chronicity and metformin treatment interact with the identified neurocognitive effects.ResultsThe UK Biobank dataset included cognitive and neuroimaging data (N = 20,314), including 1012 T2DM and 19,302 HCs, aged between 50 and 80 years. Duration of T2DM ranged from 0 to 31 years (mean 8.5 ± 6.1 years); 498 were treated with metformin alone, while 352 were unmedicated. Our meta-analysis evaluated 34 cognitive studies (N = 22,231) and 60 neuroimaging studies: 30 of T2DM (N = 866) and 30 of aging (N = 1088). Compared to age, sex, education, and hypertension-matched HC, T2DM was associated with marked cognitive deficits, particularly in executive functioning and processing speed. Likewise, we found that the diagnosis of T2DM was significantly associated with gray matter atrophy, primarily within the ventral striatum, cerebellum, and putamen, with reorganization of brain activity (decreased in the caudate and premotor cortex and increased in the subgenual area, orbitofrontal cortex, brainstem, and posterior cingulate cortex). The structural and functional changes associated with T2DM show marked overlap with the effects correlating with age but appear earlier, with disease duration linked to more severe neurodegeneration. Metformin treatment status was not associated with improved neurocognitive outcomes.ConclusionsThe neurocognitive impact of T2DM suggests marked acceleration of normal brain aging. T2DM gray matter atrophy occurred approximately 26% ± 14% faster than seen with normal aging; disease duration was associated with increased neurodegeneration. Mechanistically, our results suggest a neurometabolic component to brain aging. Clinically, neuroimaging-based biomarkers may provide a valuable adjunctive measure of T2DM progression and treatment efficacy based on neurological effects.FundingThe research described in this article was funded by the W. M. Keck Foundation (to LRMP), the White House Brain Research Through Advancing Innovative Technologies (BRAIN) Initiative (NSFNCS-FR 1926781 to LRMP), and the Baszucki Brain Research Fund (to LRMP). None of the funding sources played any role in the design of the experiments, data collection, analysis, interpretation of the results, the decision to publish, or any aspect relevant to the study. DJW reports serving on data monitoring committees for Novo Nordisk. None of the authors received funding or in-kind support from pharmaceutical and/or other companies to write this article.

Project description:BackgroundThe impact of cardiovascular risk burden on cognitive trajectories and brain structure changes remains unclear.ObjectivesThis study aimed to examine whether cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) is associated with cognitive decline and structural brain differences.MethodsWithin the Rush Memory and Aging Project, 1,588 dementia-free participants (mean age: 79.5 years) were followed for up to 21 years. FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with a battery of 19 tests, from which composite scores were derived. A subsample (n = 378) of participants underwent magnetic resonance imaging. Structural total and regional brain volumes were estimated. Data were analyzed using linear mixed-effects models and linear regression models.ResultsIn all participants, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Compared with the lowest tertile of FGCRS, the highest tertile was associated with faster decline in global cognition (β = -0.019; 95% confidence interval [CI]: -0.035 to -0.003), episodic memory (β = -0.023; 95% CI: -0.041 to -0.004), working memory (β = -0.021; 95% CI: -0.035 to -0.007), and perceptual speed (β = -0.027; 95% CI: -0.042 to -0.011) over the follow-up. In magnetic resonance imaging data analyses, higher FGCRS was related to smaller volumes of the hippocampus (β = -0.021; 95% CI: -0.042 to -0.000), gray matter (β = -1.569; 95% CI: -2.757 to -0.382), and total brain (β = -1.588; 95% CI: -2.832 to -0.344), and greater volume of white matter hyperintensities (β = 0.035; 95% CI: 0.001 to 0.069).ConclusionsHigher cardiovascular risk burden may predict decline in episodic memory, working memory, and perceptual speed and is associated with neurodegeneration and vascular lesions in the brain.

Dataset Information

Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline.

Objective

Methods

Results

Conclusions

Publications

Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline.

Similar Datasets

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