Type 2 Diabetes Accelerates Brain Aging

We conducted a three-part meta analysis of cognitive decline associated with Type-2 Diabetes Mellitus (T2DM). First, we evaluated the current literature on cognitive function, comparing T2DM patients to age-matched controls testing whether T2DM presented a case of ‘accelerated aging’, such that the cognitive gap between groups widens with age. Second, we analyzed the current literature on brain structure and function, comparing T2DM patients to healthy controls to determine if patterns of structural and functional deficits correspond to the selective distribution of GluT4 throughout the brain. Third, to address the potential for confirmation bias inherent in meta-analyses (i.e., typically positive, but not negative, results are published) we validated these findings with a large-scale (N> 25,000) hypothesis-neutral dataset, U.K. Biobank.  Participants with type 2 diabetes performed worse than age-matched controls with significant heterogeneity across available studies on tests of several domains.  Our meta-regression revealed that age was a significant moderator of effect size for processing speed (beta= 0.0148, p < 0.005, r2 =  33.16). Age was not a significant moderator of any other domain. The findings of our meta-analysis are confirmed by our analysis of UK-Biobank. We show that participants with T2DM, even after accounting for differences in age and education, consistently performed worse on various cognitive tests. Besides the effects seen in cognition, our analysis shows statistically significant atrophy, in total grey matter volume terms, for the cohort of subjects diagnosed with type 2 diabetes, compared to healthy controls, across the age spectrum and normalized for education. These results suggest that across both cognitive and neural studies, T2DM was consistently associated with worse outcomes, indicating a negative relationship between T2DM, brain function, and cognition.

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Type 2 Diabetes Accelerates Brain Aging and Cognitive Decline: Complementary findings from UK Biobank and Meta-analyses. Antal B, McMahon LP, Sultan SF, Lithen A, Wexler DJ, Dickerson BC, Ratai EM, Mujica-Parodi LR. eLife, 11, e73138 (2022). doi:10.7554/eLife.73138. PDF+SI

Type 2 Diabetes Mellitus (T2DM) is associated with strong gray matter atrophy, consistent across the whole brain. We useed structural MRI data from 940 adults with T2DM (62.4±7.5y) and 20062 control subjects (65.4±6.8y). We then utilized multivariable linear regression to address the eects of T2DM on gray matter volume (measured in voxel count) across distinct anatomical regions. After accounting for the eects of age and education, individuals with T2DM showed signicantly decreased gray matter volume in both cortical and sub-cortical regions. The strongest effects were seen in the cerebellum (T=-15.4, P=2e-51) and ventral striatum (T=-10.5, P=6e-24), both showing 5.7% decrease in gray matter volume. *P ≤ .05; **P ≤ .01; ***P ≤ .001.