Brain Atrophy in Type 2 Diabetes: Regional distribution and influence on cognition

OBJECTIVE

Type 2 diabetes (T2DM) is associated with brain atrophy and cerebrovascular disease. We aimed to define the regional distribution of brain atrophy in T2DM and to examine whether atrophy or cerebrovascular lesions are feasible links between T2DM and cognitive function.

RESEARCH DESIGN AND METHODS

This cross-sectional study used magnetic resonance imaging (MRI) scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. With voxel-based morphometry, we studied the regional distribution of atrophy in T2DM. We measured cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) while blinded to T2DM status. With use of multivariable regression, we examined for mediation or effect modification of the association between T2DM and cognitive measures by MRI measures.

RESULTS

T2DM was associated with more cerebral infarcts and lower total gray, white, and hippocampal volumes (all P < 0.05) but not with microbleeds or WMH. T2DM-related gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobes, and white matter loss was distributed in frontal and temporal regions. T2DM was associated with poorer visuospatial construction, planning, visual memory, and speed (P ≤ 0.05) independent of age, sex, education, and vascular risk factors. The strength of these associations was attenuated by almost one-half when adjusted for hippocampal and total gray volumes but was unchanged by adjustment for cerebrovascular lesions or white matter volume.

CONCLUSIONS

Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer disease. Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment.Type 2 diabetes (T2DM) is associated with an increased risk of incident cognitive impairment, dementia, and Alzheimer disease as a possible result of cerebrovascular and/or neurodegenerative disease (1–3). T2DM is associated with brain infarcts (4,5) on magnetic resonance imaging (MRI) and less consistently with cerebral white matter hyperintensities (WMHs) (6,7) and cerebral microbleeds (8,9). Lower hippocampal volume (10–12) and total brain volume (13), which are features of Alzheimer disease, are also more likely to occur in T2DM. However, few studies have clarified the regional distribution of brain atrophy attributable to T2DM (14–16). These studies were small, and only one compared people with and without T2DM, with the results suggesting that temporal lobe gray matter may be affected in T2DM (15). Understanding the pattern of brain atrophy in T2DM may provide clues toward the underlying neurodegenerative process. For example, gray matter atrophy occurs early in the temporal, parietal, and limbic cortices before spreading to involve frontal and occipital regions in Alzheimer disease (17). Moreover, although some studies demonstrated associations of T2DM with brain atrophy or cerebrovascular disease, no data describe how MRI measures of atrophy and cerebrovascular disease mediate the difference in cognitive function between those with and without T2DM. Manschot et al. (18) found an association between T2DM and more deep white matter lesions, cortical and subcortical atrophy, and infarcts as well as impaired cognitive performance. In subgroup analysis of only those with T2DM, they found that cognitive performance was inversely associated with deep white matter lesion volume, atrophy, and infarcts. In the current study, we examined the distribution of brain atrophy in older people with T2DM, predicting that MRI measures of brain atrophy and cerebrovascular disease would mediate or modify the association between T2DM and cognitive function.