Blood glucose levels and cortical thinning in cognitively normal, middle-aged adults.
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 (≥126mg/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.
Wennberg, AMV; Spira, AP; Pettigrew, C; Soldan, A; Zipunnikov, V; Rebok, GW; Roses, AD; Lutz, MW; Miller, MM; Thambisetty, M; Albert, MS
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