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Measures of Adiposity and Alzheimer's Disease-Related MRI Markers: The Northern Manhattan Study.

ABSTRACT: BACKGROUND:Adiposity may increase risk for dementia and Alzheimer's disease (AD), but mechanisms are unclear. OBJECTIVE:To examine associations between measures of adiposity with AD-signature region cortical thickness and hippocampal volume. METHODS:We used data from the Northern Manhattan Study, a clinically stroke-free cohort of mostly Hispanic participants. Exposures of interest included body mass index (BMI), waist-hip-ratio (WHR), waist circumference (WC), and adiponectin concentration, measured at study entry. AD-signature region cortical thickness and hippocampal volume were obtained using Freesurfer. We estimated associations using multivariable linear regression, adjusting for sociodemographics and health behaviors. We re-examined estimates after adjustment for APOE?4 allele status or carotid intima-media thickness (cIMT), among those cognitively unimpaired, and after weighting for the inverse probability of selection into the MRI sub-study. We also repeated analyses for cortical thickness in non-AD signature regions. RESULTS:The sample (N?=?947, 63% women, 66% Hispanic/Latino, 26% obese) had a mean (SD) age?=?63 (8) years. Greater BMI and WC (both z-scored) were associated with thinner AD-signature region cortex (also z-scored) (BMI: ? [95% CI]?=?-0.09 [-0.18, -0.01], WC: ? [95% CI]?=?-0.11 [-0.20, -0.02]). We did not find evidence that adiposity was related to hippocampal volume. Results were consistent after adjustment for APOE?4 allele status or cIMT, after weighting for selection, among those cognitively unimpaired, and for non-AD signature region cortical thickness. CONCLUSION:Greater BMI and WC were related to cortical thinning within and outside the AD-signature region, suggesting a global effect not specific to AD.

SUBMITTER: Caunca MR

PROVIDER: S-EPMC7212498 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Measures of Adiposity and Alzheimer's Disease-Related MRI Markers: The Northern Manhattan Study.

Caunca Michelle R MR Simonetto Marialaura M Alperin Noam N Elkind Mitchell S V MSV Sacco Ralph L RL Wright Clinton B CB Rundek Tatjana T

Journal of Alzheimer's disease : JAD 20190101 4

<h4>Background</h4>Adiposity may increase risk for dementia and Alzheimer's disease (AD), but mechanisms are unclear.<h4>Objective</h4>To examine associations between measures of adiposity with AD-signature region cortical thickness and hippocampal volume.<h4>Methods</h4>We used data from the Northern Manhattan Study, a clinically stroke-free cohort of mostly Hispanic participants. Exposures of interest included body mass index (BMI), waist-hip-ratio (WHR), waist circumference (WC), and adiponec ...[more]

PMID: 31306120

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Project description:BackgroundClinical and epidemiological studies of older persons have implicated clusterin in Alzheimer's disease (AD) pathogenesis. In the context of identifying early biomarkers of risk, we examined associations of plasma clusterin and characteristics of AD in middle-aged individuals from the community.Materials and methodsSubjects were 639 cognitively normal individuals (mean age 50 ± 3.5) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Clusterin was quantified using ELISA (mean 255± 31 ng/ml). Associations were assessed between clusterin and volumes of brain regions known to atrophy in early AD, including entorhinal cortex (ECV), hippocampus (HV), and medial temporal lobe (MTLV) volumes (cm3). Total brain volume (TBV) and volumes of structures affected in later AD were examined for comparison.ResultsIn multivariable models, higher clusterin had a negative non-linear association with ECV (combined left and right hemispheres), and this association was influenced by the highest clusterin levels. Compared to mean clusterin, 1 and 2 standard deviation (SD) level increases in clusterin were associated with -2.1% (95% CI: -3.3,-0.9) and -7.3% (95% CI: -11.3,-3.3) lower ECV, respectively. Similar relationships were observed between clusterin and HV, although the relationship was stronger for left-side HV than the right-side. However, the association was not significant after adjusting for covariates. Negative non-linear associations between clusterin and MTLV were strongest for the left side: compared to mean clusterin, 1 and 2 SD level increases in clusterin were associated with -0.9% (95% CI: -1.9, 0.1) and -3.7% (95% CI: -7.1, -0.3) lower MTLV. There were no significant associations between clusterin and brain structures affected in later AD.ConclusionsIn middle-aged adults unselected for AD, plasma clusterin was associated with lower volume of the entorhinal cortex, an area that atrophies early in AD. Clusterin could be informative as part of a multi-component preclinical marker for AD.

Dataset Information

Measures of Adiposity and Alzheimer's Disease-Related MRI Markers: The Northern Manhattan Study.

Publications

Measures of Adiposity and Alzheimer's Disease-Related MRI Markers: The Northern Manhattan Study.

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