TY - JOUR
T1 - Blood glucose levels and cortical thinning in cognitively normal, middle-aged adults
AU - Wennberg, Alexandra M.V.
AU - Spira, Adam P.
AU - Pettigrew, Corinne
AU - Soldan, Anja
AU - Zipunnikov, Vadim
AU - Rebok, George W.
AU - Roses, Allen D.
AU - Lutz, Michael W.
AU - Miller, Michael M.
AU - Thambisetty, Madhav
AU - Albert, Marilyn S.
N1 - Funding Information:
Conflict of interests: Drs. Wennberg, Pettigrew, Soldan, Zipunnikov, Rebok, Lutz, Miller, Thambisetty, and Albert report no conflicts of interest. Dr. Spira has received grants from the National Institute on Aging, Johns Hopkins University, and the William and Ella Owens Medical Research Foundation. Dr. Roses is the Jefferson-Pilot Professor of Neurosciences and Neurology at Duke University. Dr. Roses is the CEO and sole shareholder of Zinfandel Pharmaceuticals, Inc. (a NC S-Corp). Zinfandel is an alliance with Takeda Pharmaceuticals to manage the TOMMORROW study.
Funding Information:
This study was supported in part by grants from the National Institutes of Health ( U19-AG03365 , P50-AG005146 , and T32-AG027668 ). The BIOCARD Study consists of 7 Cores with the following members: (1) the Administrative Core (Marilyn Albert, Barbara Rodzon); (2) the Clinical Core (Ola Selnes, Marilyn Albert, Anja Soldan, Rebecca Gottesman, Ned Sacktor, Guy McKhann, Scott Turner, Leonie Farrington, Maura Grega, Gay Rudow, Daniel D'Agostino, Scott Rudow); (3) the Imaging Core (Michael Miller, Susumu Mori, Tilak Ratnanather, Timothy Brown, Hayan Chi, Anthony Kolasny, Kenichi Oishi, Thomas Reigel, Laurent Younes); (4) the Biospecimen Core (Abhay Moghekar, Richard O′Brien, Abby Spangler); (5) the Informatics Core (Roberta Scherer, David Shade, Ann Ervin, Jennifer Jones, Matt Toepfner, Lauren Parlett, April Patterson, Aisha Mohammed); (6) the Biostatistics Core (Mei-Cheng Wang, Qing Cai, Daisy Lu); and (7) the Neuropathology Core (Juan Troncoso, Barbara Crain, Olga Pletnikova, Gay Rudow, and Karen Fisher). The authors are grateful to the members of the BIOCARD Scientific Advisory Board who provide continued oversight and guidance regarding the conduct of the study including: Drs John Cernansky, David Holtzman, David Knopman, Walter Kukull, and John McArdle, and Drs Neil Buckholtz, John Hsiao, Laurie Ryan, and Jovier Evans, who provide oversight on behalf of the National Institute on Aging and the National Institute of Mental Health (NIMH), respectively. The authors thank the members of the BIOCARD Resource Allocation Committee who provide ongoing guidance regarding the use of the biospecimens collected as part of the study, including: Drs Constantine Lyketsos, Carlos Pardo, Gerard Schellenberg, Leslie Shaw, Madhav Thambisetty, and John Trojanowski.
Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.
PY - 2016/6/15
Y1 - 2016/6/15
N2 - 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.
AB - 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.
KW - APOE
KW - Alzheimer's disease
KW - Blood glucose
KW - Cortical thinning
KW - TOMM40
UR - http://www.scopus.com/inward/record.url?scp=84964329895&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964329895&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2016.04.017
DO - 10.1016/j.jns.2016.04.017
M3 - Article
C2 - 27206882
AN - SCOPUS:84964329895
SN - 0022-510X
VL - 365
SP - 89
EP - 95
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
ER -