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August 02, 2011; 77 (5) Articles

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

S. Debette, S. Seshadri, A. Beiser, R. Au, J.J. Himali, C. Palumbo, P.A. Wolf, C. DeCarli
First published August 1, 2011, DOI: https://doi.org/10.1212/WNL.0b013e318227b227
S. Debette
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S. Seshadri
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A. Beiser
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R. Au
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J.J. Himali
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C. Palumbo
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P.A. Wolf
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C. DeCarli
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Citation
Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline
S. Debette, S. Seshadri, A. Beiser, R. Au, J.J. Himali, C. Palumbo, P.A. Wolf, C. DeCarli
Neurology Aug 2011, 77 (5) 461-468; DOI: 10.1212/WNL.0b013e318227b227

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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.

GLOSSARY

ARIC=
Atherosclerosis Risk in Communities;
BMI=
body mass index;
DSM-IV=
Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
LM-d=
Logical Memory, delayed recall;
NP=
neuropsychological test battery;
TBV=
total brain volume;
THV=
temporal horn volume;
TrB-A=
Trail-Making Test B-A;
VR-d=
delayed recall component of the Visual Reproductions test;
WMHV=
white matter hyperintensity volume

Footnotes

  • Study funding: This work (design and conduct of the study, collection and management of the data) was supported by the Framingham Heart Study's National Heart, Lung, and Blood Institute contract (N01-HC-25195) and by grants from the National Institute of Neurological Disorders and Stroke (R01 NS17950) and from the National Institute on Aging (R01 AG16495; AG08122; AG033193; AG031287). Dr. Debette was supported by a Fulbright grant and received an award from the Bettencourt-Schueller Foundation.

  • Supplemental data at www.neurology.org

  • Received January 2, 2011.
  • Accepted April 5, 2011.
  • Copyright © 2011 by AAN Enterprises, Inc.
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