期刊
FRONTIERS IN NEUROLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fneur.2021.551975
关键词
prediabetes; sex; brain metabolism; Alzheimer' s disease; hippocampal volume; amyloid-beta; phosphorylated tau; cognitive function
资金
- California Department of Public Health [19-10613]
- NIH [R01 AG049810]
- Alzheimer's Association [AARF-17-528918, AARG-18-566254, AARG-17-500358]
- U.S. Department of Veterans Affairs Clinical Sciences Research and Development Service (Career Development Award-2) [1IK2CX001415, IK2CX001865, I01 CX001842]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- Biogen
- CereSpir, Inc.
- Cogstate
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- Fujirebio
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Merck Co., Inc.
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- ADNI clinical sites in Canada
- Foundation for the National Institutes of Health
- Northern California Institute for Research and Education
- Laboratory for Neuro Imaging at the University of Southern California
- AbbVie
- Alzheimer's Association
- BioClinica, Inc
- BristolMyers Squibb Company
- Eisai Inc.
- F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Lumosity
- Lundbeck
- Meso Scale Diagnostics, LLC.
- Neurotrack Technologies
- Servier
- Transition Therapeutics
The study found that prediabetes may affect cognition through altered brain metabolism, and that women may be more vulnerable to the negative effects of glucose intolerance.
Although type 2 diabetes is a well-known risk factor for Alzheimer's disease (AD), little is known about how its precursor-prediabetes-impacts neuropsychological function and brain health. Thus, we examined the relationship between prediabetes and AD-related biological and cognitive/clinical markers in a well-characterized sample drawn from the Alzheimer's Disease Neuroimaging Initiative. Additionally, because women show higher rates of AD and generally more atherogenic lipid profiles than men, particularly in the context of diabetes, we examined whether sex moderates any observed associations. The total sample of 911 nondemented and non-diabetic participants [normal control = 540; mild cognitive impairment (MCI) = 371] included 391 prediabetic (fasting blood glucose: 100-125 mg/dL) and 520 normoglycemic individuals (age range: 55-91). Linear mixed effects models, adjusted for demographics and vascular and AD risk factors, examined the independent and interactive effects of prediabetes and sex on 2-6 year trajectories of FDG-PET measured cerebral metabolic glucose rate (CMRglu), hippocampal/intracranial volume ratio (HV/IV), cerebrospinal fluid phosphorylated tau-(181)/amyloid-beta(1-42) ratio (p-tau(181)/A beta(1-42)), cognitive function (executive function, language, and episodic memory) and the development of dementia. Analyses were repeated in the MCI subsample. In the total sample, prediabetic status had an adverse effect on CMRglu across time regardless of sex, whereas prediabetes had an adverse effect on executive function across time in women only. Within the MCI subsample, prediabetic status was associated with lower CMRglu and poorer executive function and language performance across time within women, whereas these associations were not seen within men. In the total sample and MCI subsample, prediabetes did not relate to HV/IV, p-tau(181)/A beta(1-42), memory function or dementia risk regardless of sex; however, among incident dementia cases, prediabetic status related to earlier age of dementia onset in women but not in men. Results suggest that prediabetes may affect cognition through altered brain metabolism, and that women may be more vulnerable to the negative effects of glucose intolerance.
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