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Higher normal fasting plasma glucose is associated with hippocampal atrophy

The PATH Study

  1. Kaarin J. Anstey, PhD
  1. 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.
  1. Correspondence & reprint requests to Dr. Cherbuin nicolas.cherbuin{at}anu.edu.au
Scientific Advisory Boards:

  1. NONE

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  1. NONE

Funding for Travel or Speaker Honoraria:

  1. NONE

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. NONE

Speakers’ Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

Legal Proceedings:

  1. NONE

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. NONE

Editorial Boards:

  1. American Journal of Geriatric Psychiatry, Editorial Board, 2008-11 Acta Neuropsychiatrica, Editorial Board, 2006-11 Neuropsychiatric Disorders and Treatment, 2005-11 Current Opinion in Psychiatry, Section editor, 2008-12

Patents:

  1. NONE

Publishing Royalties:

  1. The Yipping Tiger and Other tales from the Neuropsychiatry clinic, University of New South Wales Press, 2009 Secondary Schizophrenia, Cambridge University Press, 2010 Akathisia and Restless legs, Cambridge University Press, 1993. The Ageing Brain, Wiley, 2000. Speakers’ Bureaus: Talk in 2011 to the Queensland Neuropsychiatry Group (sponsored by Eli Lilly). Talk to Alzheimer’s Master Class 2009 (sponsored by Pfizer)

Employment, Commercial Entity:

  1. NONE

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  1. NONE

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  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NHMRC Capacity Building Grant – ID No 568940 – Sachdev P, Brodaty H, Andrews G, Lord S. Prevention and management of mental disorders in Older Australians. 5 years – 2009- 2013. UNSW Goldstar – ID No. 568785 – Sachdev P, Easteal S, Wen W. Neurocognitive and physical health in extreme old age: Sydney Centenarian Study – 1 year – 2009. NHMRC Program Grant – ID No. 568969 – Sachdev P, Brodaty H, Andrews G. The prevention early detection and effective management of neurocognitive disorders in the elderly. 2010-2014. NHMRC Project Grant – ID No. 630592 – Sachdev P, Richmond R, Kochan N, Wen W, Crawford J. A cognitive and neuroimaging study of exceptionally old individuals: Sydney Centenarian Study. 3 years - 2010-2012. Department of Health & Ageing. Dementia Collaborative Research Centre – Assessment and Better Care, Centre Funding – 2010-2013 - (4 years) (Brodaty / Sachdev / Broe / Draper). Department of Innovation, Industry, Science & Research (DIISR). Collaborative Research Networks Grant - – 2011-2013 (3 years) (Lead CI/Institution: Prof Annabelle Duncan/University of New England (UNE); Kelly B - UoN; Llewellyn G – USyd; Pitts M – LaTrobe; Moran G - UNSW); Sachdev P (AI). CSIRO Flagship Project Grant. SNP and CNV analysis of discordant neuropsychiatric and brain imaging traits in twins from the Older Australians Twin Study (OATS). – 2011 - (1 year) (Sachdev / Mather / Dusing).

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. Pacific Alzheimer Research Foundation (PARF) Operating Grant – ID No. PARF OP06-04-Beg. Improving sensitivity of early detection of Alzheimer’s disease (AD) via multi- dimensional analysis of longitudinal MRI scans. 3 years - 2007-2009.

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

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  1. NONE

Legal Proceedings:

  1. Occasional expert opinion on medicolegal matters not related to the present study.

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  1. NONE

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. 1) Commercial entity - Pfizer - speaker honoraria

Editorial Boards:

  1. Editorial Board member of the following journals: Aging, Neuropsychology and Cognition, Journals of Gerontology: Psychological Science; Ageing International; Gertontology; European Journal on Ageing

Patents:

  1. NONE

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  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. 1) Non-profit entity: Australian Capital Territory Government 2) Non-profit entity: Alzheimer’s Australia 3) Commercial entity: Suncorp Insurance

Speakers’ Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. 1)NHMRC of Australia Grant No. 973302, 179805, 157125, and from an Australian Rotary Health Research Fund grant. NC and KA are funded by Fellowships No. 471501 and 366756

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

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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.
  1. doi: 10.1212/WNL.0b013e31826846de Neurology vol. 79 no. 10 1019-1026
  1. » Abstract
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  3. Full Text
  4. Full Text (PDF)
  5. Data Supplement
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