Associations of Regional Brain Structural Differences With Aging, Modifiable Risk Factors for Dementia, and Cognitive Performance | Dementia and Cognitive Impairment | JAMA Network Open | JAMA Network
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    Original Investigation
    Geriatrics
    December 11, 2019

    Associations of Regional Brain Structural Differences With Aging, Modifiable Risk Factors for Dementia, and Cognitive Performance

    Author Affiliations
    • 1Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
    • 2Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
    • 3Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom
    • 4United Kingdom Dementia Research Institute, London, United Kingdom
    • 5Data Science Institute, Imperial College London, London, United Kingdom
    • 6Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom
    JAMA Netw Open. 2019;2(12):e1917257. doi:10.1001/jamanetworkopen.2019.17257
    Key Points español 中文 (chinese)

    Question  Are aging and modifiable risk factors for dementia (MRFD) associated with volume differences in brain regions also associated with Alzheimer disease (AD)?

    Findings  In this cross-sectional study including 8312 participants, 4 MRFD (hypertension, diabetes, obesity, and frequent alcohol use) were independently and negatively associated with overlapping gray matter regions, including the posterior cingulate cortex, which overlapped with regions that are known to show atrophy in AD. The negative associations of MRFD with spatial memory were associated with mediation through differences in posterior cingulate cortex volume.

    Meaning  These findings suggest that common brain regions associated with change with aging and MRFD may explain their joint contributions to cognitive variances in people considered cognitively healthy and in people with AD.

    Abstract

    Importance  Identifying brain regions associated with risk factors for dementia could guide mechanistic understanding of risk factors associated with Alzheimer disease (AD).

    Objectives  To characterize volume changes in brain regions associated with aging and modifiable risk factors for dementia (MRFD) and to test whether volume differences in these regions are associated with cognitive performance.

    Design, Setting, and Participants  This cross-sectional study used data from UK Biobank participants who underwent T1-weighted structural brain imaging from August 5, 2014, to October 14, 2016. A voxelwise linear model was applied to test for regional gray matter volume differences associated with aging and MRFD (ie, hypertension, diabetes, obesity, and frequent alcohol use). The potential clinical relevance of these associations was explored by comparing their neuroanatomical distributions with the regional brain atrophy found with AD. Mediation models for risk factors, brain volume differences, and cognitive measures were tested. The primary hypothesis was that common, overlapping regions would be found. Primary analysis was conducted on April 1, 2018.

    Main Outcomes and Measures  Gray matter regions that showed relative atrophy associated with AD, aging, and greater numbers of MRFD.

    Results  Among 8312 participants (mean [SD] age, 62.4 [7.4] years; 3959 [47.1%] men), aging and 4 major MRFD (ie, hypertension, diabetes, obesity, and frequent alcohol use) had independent negative associations with specific gray matter volumes. These regions overlapped neuroanatomically with those showing lower volumes in participants with AD, including the posterior cingulate cortex, the thalamus, the hippocampus, and the orbitofrontal cortex. Associations between these MRFD and spatial memory were mediated by differences in posterior cingulate cortex volume (β = 0.0014; SE = 0.0006; P = .02).

    Conclusions and Relevance  This cross-sectional study identified differences in localized brain gray matter volume associated with aging and MRFD, suggesting regional vulnerabilities. These differences appeared relevant to cognitive performance even among people considered cognitively healthy.

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