title: 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 (≥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.
authors.affiliation: Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205, United States. Electronic address: wennberg.alexandra@mayo.edu.
authors.forename: Alexandra M V
authors.initials: AM
authors.lastname: Wennberg
authors.affiliation: Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205, United States; Department of Psychiatry and Behavioral Science, Johns Hopkins School of Medicine, 733 N. Broadway, Baltimore, MD 21205, United States; Johns Hopkins Center on Aging and Health, 2024 E. Monument St., Baltimore, MD 21205, United States. Electronic address: aspira@jhu.edu.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Spira
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, 733 N. Broadway, Baltimore, MD 21205, United States. Electronic address: cpettigrew@jhmi.edu.
authors.forename: Corinne
authors.initials: C
authors.lastname: Pettigrew
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, 733 N. Broadway, Baltimore, MD 21205, United States. Electronic address: asoldan1@jhmi.edu.
authors.forename: Anja
authors.initials: A
authors.lastname: Soldan
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205, United States; Johns Hopkins Center on Aging and Health, 2024 E. Monument St., Baltimore, MD 21205, United States. Electronic address: vadim.zipunnikov@gmail.com.
authors.forename: Vadim
authors.initials: V
authors.lastname: Zipunnikov
authors.affiliation: Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205, United States; Department of Psychiatry and Behavioral Science, Johns Hopkins School of Medicine, 733 N. Broadway, Baltimore, MD 21205, United States; Johns Hopkins Center on Aging and Health, 2024 E. Monument St., Baltimore, MD 21205, United States. Electronic address: grebok1@jhu.edu.
authors.forename: George W
authors.initials: GW
authors.lastname: Rebok
authors.affiliation: Department of Neurology, Duke University School of Medicine, 8 Searle Center Dr., Durham, NC 27703, United States. Electronic address: allen.roses@duke.edu.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Roses
authors.affiliation: Department of Neurology, Duke University School of Medicine, 8 Searle Center Dr., Durham, NC 27703, United States. Electronic address: michael.lutz@duke.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Lutz
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, United States. Electronic address: mim@cis.jhu.edu.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Miller
authors.affiliation: Unit of Clinical and Translational Neuroscience, National Institute on Aging, 251 Bayview Blvd, Baltimore, MD 21224, United States. Electronic address: thambisettym@mail.nih.gov.
authors.forename: Madhav
authors.initials: M
authors.lastname: Thambisetty
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, 733 N. Broadway, Baltimore, MD 21205, United States. Electronic address: malbert9@jhmi.edu.
authors.forename: Marilyn S
authors.initials: MS
authors.lastname: Albert
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics; D001786:Blood Glucose / Q000235:genetics; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000473:pathology; D003071:Cognition; D003430:Cross-Sectional Studies; D005215:Fasting; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009929:Organ Size
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human
keywords: APOE; Alzheimer's disease; Blood glucose; Cortical thinning; TOMM40