Association between Type 2 Diabetes Mellitus and Brain Atrophy: A Meta-Analysis

Abstract

Background: Type 2 diabetes mellitus (T2DM) is known to be associated with cognitive decline and brain structural changes. This study systematically reviews and estimates human brain volumetric differences and atrophy associated with T2DM.

Methods: PubMed, PsycInfo and Cochrane Library were searched for brain imaging studies reporting on brain volume differences between individuals with T2DM and healthy controls. Data were examined using meta-analysis, and association between age, sex, diabetes characteristics and brain volumes were tested using meta-regression.

Results: A total of 14,605 entries were identified; after title, abstract and full-text screening applying inclusion and exclusion criteria, 64 studies were included and 42 studies with compatible data contributed to the meta-analysis (n=31,630; mean age 71.0 years; 44.4% male; 26,942 control; 4,688 diabetes). Individuals with T2DM had significantly smaller total brain volume, total grey matter volume, total white matter volume and hippocampal volume (approximately 1% to 4%); meta-analyses of smaller samples focusing on other brain regions and brain atrophy rate in longitudinal investigations also indicated smaller brain volumes and greater brain atrophy associated with T2DM. Meta-regression suggests that diabetes-related brain volume differences start occurring in early adulthood, decreases with age and increases with diabetes duration.

Conclusion: T2DM is associated with smaller total and regional brain volume and greater atrophy over time. These effects are substantial and highlight an urgent need to develop interventions to reduce the risk of T2DM for brain health.

Keywords: Atrophy; Brain; Diabetes mellitus, type 2; Neuroimaging.

Fig. 1

Flowchart of the screening and inclusion of studies into the systematic review and meta-analysis.

Fig. 2

Forest plots of differences in global brain volumes and total brain atrophy rate between participants with and without type 2 diabetes mellitus. (A) Total brain volume difference, (B) grey matter volume difference, (C) white matter volume difference, (D) total brain atrophy difference. CI, confidence interval.

Fig. 3

Funnel plots of brain volumes and atrophy rate assessing possible publication bias using the trim and fill method. Filled circles represent studies included in the meta-analysis. Open circles represent possible missing studies. Brain volumes: (A) total brain volume, (B) grey matter, (C) white matter, (D) hippocampus, (E) thalamus, (F) caudate, (G) putamen, (H) globus pallidus, (I) amygdala, (J) nucleus accumbens, (K) superior temporal gyrus, (L) frontal lobe, (M) cerebrospinal fluid, (N) white matter hyperintensity, and (O) total brain atrophy rate._(Continued to the next page)