Blood glucose levels and cortical thinning in cognitively normal, middle-aged adults

Abstract

Type II diabetes mellitus (DM) increases risk for cognitive decline and is associated with brain atrophy in older demented and non-demented individuals. We investigated (1) the cross-sectional association between fasting blood glucose level and cortical thickness in a sample of largely middle-aged, cognitively normal adults, and (2) whether these associations were modified by genes associated with both lipid processing and dementia. To explore possible modifications by genetic status, we investigated the interaction between blood glucose levels and the apolipoprotein E (APOE) ε4 allele and the translocase of the outer mitochondrial membrane (TOMM) 40 ′523 genotype on cortical thickness. Cortical thickness measures were based on mean thickness in a subset of a priori-selected brain regions hypothesized to be vulnerable to atrophy in Alzheimer's disease (AD) (i.e., ‘AD vulnerable regions’). Participants included 233 cognitively normal subjects in the BIOCARD study who had a measure of fasting blood glucose and cortical thickness measures, quantified by magnetic resonance imaging (MRI) scans. After adjustment for age, sex, race, education, depression, and medical conditions, higher blood glucose was associated with thinner parahippocampal gyri (B = −0.002; 95% CI −0.004, −0.0004) and temporal pole (B = −0.002; 95% CI −0.004, −0.0001), as well as reduced average thickness over AD vulnerable regions (B = −0.001; 95% CI −0.002, −0.0001). There was no evidence for greater cortical thinning in ε4 carriers of the APOE gene or in APOE ε3/3 individuals carrying the TOMM40 VL/VL genotypes. When individuals with glucose levels in the diabetic range (≥126 mg/dL), were excluded from the analysis, the associations between glucose levels and cortical thickness were no longer significant. These findings suggest that glucose levels in the diabetic range are associated with reduced cortical thickness in AD vulnerable regions as early as middle age.

Metabolic and hormone influences on emotion processing during menopause

“…When we divided our group into “higher” and “lower” HbA1c levels, relationships between HbA1c and TPO junction activation and reaction time to emotionally neutral images were found to exist only in women with higher HbA1c levels, with mean HbA1c falling within pre-diabetic range. Similar threshold effects have been found for other relationships between metabolic measures and neural outcomes, for example glucose levels are associated with reduced cortical thickness in Alzheimer’s Disease only in patients with glucose levels in the diabetic range (Wennberg et al, 2016). Our results suggest that the negative interpretation bias associated with increased recruitment of cognitive association regions during emotional decision-making may be driven by metabolic dysfunction during menopause.…”

Atrophy in Distributed Networks Predicts Cognition in Alzheimer’s Disease and Type 2 Diabetes

“…In a prospective study of non-demented adults, insulin resistance at baseline predicted subsequent atrophy of the hippocampus and parahippocampal gyrus and impaired performance on RAVLT encoding trials [13]. In healthy adults, hyperglycemia is associated with cortical thinning in AD-associated regions including the parahippocampal gyrus and temporal pole [74]. Furthermore, in observational studies, T2DM almost doubled the risk of developing AD [75].…”

Cognitive dysfunction: A growing link between diabetes and Alzheimer's disease

“…In vivo (other than mice and rats) (Pruzin et al, 2017) Biomarkers of AD are increased in case of insulin resistant adults United States 2016 (Hoscheidt et al, 2016) Correlation between blood glucose and cortical thickness in adults United States 2016 (Wennberg et al, 2016) Mild cognitive impairment to AD as a growing risk factor in case of DM DM and possible biomarkers in neurodegeneration Australia 2015 (Moran et al, 2015) 8…”