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September 04, 2012; 79 (10) Articles

Higher normal fasting plasma glucose is associated with hippocampal atrophy

The PATH Study

Nicolas Cherbuin, Perminder Sachdev, Kaarin J. Anstey
First published September 3, 2012, DOI: https://doi.org/10.1212/WNL.0b013e31826846de
Nicolas Cherbuin
From the Centre for Research on Ageing, Health and Wellbeing (N.C., K.J.A.), Australian National University, Canberra, Australia; and School of Psychiatry (P.S.), University of New South Wales, Sydney, Australia.
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Perminder Sachdev
From the Centre for Research on Ageing, Health and Wellbeing (N.C., K.J.A.), Australian National University, Canberra, Australia; and School of Psychiatry (P.S.), University of New South Wales, Sydney, Australia.
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Kaarin J. Anstey
From the Centre for Research on Ageing, Health and Wellbeing (N.C., K.J.A.), Australian National University, Canberra, Australia; and School of Psychiatry (P.S.), University of New South Wales, Sydney, Australia.
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Citation
Higher normal fasting plasma glucose is associated with hippocampal atrophy
The PATH Study
Nicolas Cherbuin, Perminder Sachdev, Kaarin J. Anstey
Neurology Sep 2012, 79 (10) 1019-1026; DOI: 10.1212/WNL.0b013e31826846de

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Abstract

Objectives: Substantial evidence showing an association between type 2 diabetes (T2D) and cerebral atrophy, cognitive impairment, and dementia is accumulating. However, relatively little is known about the subclinical effects of high plasma glucose levels within the normal range. The aim of this study was to investigate the association between plasma glucose levels and hippocampal and amygdalar atrophy in a sample of 266 cognitively healthy individuals free of T2D, aged 60–64 years, taking part in a longitudinal study of aging.

Methods: Fasting plasma glucose was assessed at wave 1. Hippocampal and amygdalar volumes were manually traced on 1.5 T MRI scans collected at wave 1 and at wave 2 4 years later. General linear model analyses were used to assess the relationship between plasma glucose and incident medial temporal lobe atrophy after controlling for a range of sociodemographic and health variables.

Results: Plasma glucose levels were found to be significantly associated with hippocampal and amygdalar atrophy and accounted for 6%–10% in volume change after controlling for age, sex, body mass index, hypertension, alcohol, and smoking.

Conclusions: High plasma glucose levels within the normal range (<6.1 mmol/L) were associated with greater atrophy of structures relevant to aging and neurodegenerative processes, the hippocampus and amygdala. These findings suggest that even in the subclinical range and in the absence of diabetes, monitoring and management of plasma glucose levels could have an impact on cerebral health. If replicated, this finding may contribute to a reevaluation of the concept of normal blood glucose levels and the definition of diabetes.

GLOSSARY

BMI=
body mass index;
CRP=
C-reactive protein;
FOV=
field of view;
GLM=
general linear model;
HPA=
hypothalamic-pituitary-adrenal;
ICV=
intracranial volume;
IGT=
impaired glucose tolerance;
MetS=
metabolic syndrome;
ROI=
region of interest;
T2D=
type 2 diabetes;
TE=
echo time;
TR=
repetition time

Footnotes

  • Study funding: Supported by NHMRC of Australia grants 973302, 179805, and 157125 and by an Australian Rotary Health Research Fund grant. Nicolas Cherbuin and Kaarin Anstey are funded by NHMRC Research Fellowships 471501 and 1002560. This research was partly undertaken at the National Computational Infrastructure facility in Canberra, Australia, which is supported by the Australian Commonwealth Government.

  • Supplemental data at www.neurology.org

  • Received January 18, 2012.
  • Accepted April 19, 2012.
  • Copyright © 2012 by AAN Enterprises, Inc.
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