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. 2012 Mar;35(3):488-94.
doi: 10.2337/dc11-2075. Epub 2012 Feb 1.

Impaired insulin sensitivity as indexed by the HOMA score is associated with deficits in verbal fluency and temporal lobe gray matter volume in the elderly

Christian Benedict  1 , Samantha J Brooks, Joel Kullberg, Jonathan Burgos, Matthew J Kempton, Richard Nordenskjöld, Ruta Nylander, Lena Kilander, Suzanne Craft, Elna-Marie Larsson, Lars Johansson, Håkan Ahlström, Lars Lind, Helgi B Schiöth
Affiliations

Impaired insulin sensitivity as indexed by the HOMA score is associated with deficits in verbal fluency and temporal lobe gray matter volume in the elderly

Christian Benedict et al. Diabetes Care. 2012 Mar.

Abstract

Objective: Impaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

Research design and methods: Insulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).

Results: The HOMA-IR was negatively correlated with verbal fluency performance, brain size, and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.

Conclusions: These cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.

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Figures

Figure 1
Figure 1
Subject inclusionary criteria and sample sizes. Initially, 1,016 individuals (509 females) were examined at age 70 years. From these individuals, 409 underwent an MRI whole-brain scan at age 75. At the same age, the participant’s ability to generate spontaneously words of a certain category was tested by means of a VF task. To ensure a cognitively healthy population, those participants with a history of dementia or stroke, a diagnosis of type 1 or type 2 diabetes, a BMI >3 SD, pathological lesions on MRI (including arachnoidal cyst, bilateral hygroma, meningioma, and schwannoma), and who scored <27 on the mini–mental state examination (MMSE) to control for mild cognitive impairment were excluded. Furthermore, we examined each individual’s MRI scan and excluded one that was affected by movement artifacts. Thus, 285 elderly men and women were considered eligible to analyze the association between the HOMA-IR, cognitive functions, and gray matter volume at age 75 years.
Figure 2
Figure 2
Insulin resistance is linked to deficits in temporal lobe gray matter volume in elderly men and women. VBM in 285 elderly men and women aged 75 years illustrates a significant inverse association between insulin resistance as indexed by the HOMA-IR and two major clusters situated in the left and right temporal lobe of the brain, as indicated by colored areas. A: Basic regression model rendering controlled for sex and TIV. B: Complex regression model further controlled for education, serum LDL concentration, mean arterial BP, and abdominal visceral fat volume as covariates of no interest. Neurologic sections were focused at the significant peak voxels (MNI coordinates shown in brackets), and the colored bar indicates the t values. All clusters illustrated were thresholded at P < 0.05 by using FWE. R, right brain hemisphere; L, left brain hemisphere. (A high-quality digital representation of this figure is available in the online issue.)
See this image and copyright information in PMC

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