Progression of brain atrophy and

cognitive decline in diabetes mellitus

A 3-year follow-up
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S.G.C. van Elderen, MD,

A. de Roos, MD,
A.J.M. de Craen, PhD,
R.G.J. Westendorp, MD,
G.J. Blauw, MD,
J.W. Jukema, MD,
E.L.E.M. Bollen, MD,
H.A.M. Middelkoop, MD,
M.A. van Buchem, MD and
J. van der Grond, PhD
+AUTHOR

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AFFILIATIONS
1. From the Departments of Radiology (S.G.C.v.E., A.d.R., M.A.v.B., J.v.d.G.), Gerontology
and Geriatrics (A.J.M.d.C., R.G.J.W., G.J.B.), Cardiology (J.W.J.), and Neurology
(E.L.E.M.B., H.A.M.M.), Leiden University Medical Center, Leiden; Netherlands
Consortium of Healthy Ageing (R.G.J.W.), Leiden; and Durrer Center for Cardiogenetic
Research (J.W.J.), Amsterdam, the Netherlands.
Address correspondence and reprint requests to Dr. Saskia G.C. van Elderen, Department of
Radiology, Leiden University Medical Center, Postbus 9600, 2300 RC, Leiden, the Netherlands

doi: http://dx.doi.org/10.1212/WNL.0b013e3181f25f06

Neurology September 14, 2010 vol. 75 no. 11 997-1002

Abstract

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ABSTRACT
Objective: To investigate progression of MRI-assessed manifestations of cerebral
degeneration related to cognitive changes in a population of elderly patients with
diabetes mellitus (DM) compared to age-matched control subjects.
Methods: From a randomized controlled trial (PROSPER study), a study sample of 89
patients with DM and 438 control subjects without DM aged 7082 years were included
for brain MRI scanning and cognitive function testing at baseline and reexamination after
3 years. Changes in brain atrophy, white matter hyperintensities (WMHs), number of
infarctions, and cognitive function test results were determined in patients with DM and
subjects without DM. Linear regression analysis was performed with correction for age,
gender, hypertension, pravastatin treatment, educational level, and baseline test results.
In patients with DM, baseline MRI parameters were correlated with change in cognitive
function test result using linear regression analysis with covariates age and gender.
Results: Patients with DM showed increased progression of brain atrophy (p < 0.01)
after follow-up compared to control subjects. No difference in progression of WMH volume
or infarctions was found. Patients with DM showed increased decline in cognitive
performance on Stroop Test (p = 0.04) and Picture Learning Test (p = 0.03). Furthermore,
in patients with DM, change in Picture Learning Test was associated with baseline brain
atrophy (p < 0.02).
Conclusion: Our data show that elderly patients with DM without dementia have
accelerated progression of brain atrophy with significant consequences in cognition
compared to subjects without DM. Our findings add further evidence to the hypothesis
that diabetes exerts deleterious effects on neuronal integrity.

FOOTNOTES

Study funding: Supported by the Netherlands Consortium for Healthy Ageing (050
60 810) and the Netherlands Genomics Initiative ((05040202). The original study, up until
2003, was an investigator-driven trial funded by an unrestricted grant from Bristol-Myers
Squibb, which did not have influence on the data or manuscript.
Disclosure: Author disclosures are provided at the end of the article.
Received January 29, 2010. Accepted in final form May 18, 2010.