Insulin resistance was linked to decreased brain glucose metabolism and predicted worse memory function among late-middle-aged adults at risk for Alzheimer’s disease, researchers reported online July 27 in JAMA Neurology.
Based on the findings, “midlife may be a critical period for initiating treatments aimed at preventing or delaying the onset of Alzheimer’s disease,” said Auriel A. Willette, Ph.D., of Iowa State University, Ames, and his associates. Targeting insulin signaling might affect central glucose metabolism and should be studied in presymptomatic Alzheimer’s disease (AD), the researchers added.
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Insulin is now known to play a key role in the brain, and patients with type 2 diabetes are at increased risk of AD, the investigators noted. They performed cognitive testing, blood assays, and fludeoxyglucose F 18 (FDG)–labeled positron emission tomography (PET) for 150 cognitively normal, late-middle-aged adults who averaged almost 61 years old. In all, 72% of participants were women, 69% had a parent with AD, about 41% had an APOE E4 allele, and almost 5% had type 2 diabetes mellitus, the investigators reported (JAMA Neurol. 2015 Jul. 27 [doi:10.1001/jamaneurol.2015.0613]). Based on the homeostatic model assessment, increased peripheral insulin resistance was significantly associated with decreased glucose metabolism, both globally (P < .01) and in large areas of the frontal, lateral parietal, and medial and lateral temporal lobes (all P < .05), Dr. Willette and his associates found.
Insulin resistance and lower glucose uptake were especially robustly associated in the left medial temporal lobe (R2 = 0.178; P < .05), and lower glucose metabolism in this lobe was associated with worse immediate and delayed memory performance factors (P < .001 for both). “This finding provides a potential link between insulin resistance and cognitive decline,” they wrote.
The findings also support results from previous studies of older adults that have linked insulin resistance, hyperglycemia, and diabetes mellitus to hypometabolism on FDG-PET. “Insulin resistance and hyperglycemia are related conditions, and hyperglycemia, even in the prediabetic range, is associated with a significantly increased risk for later development of dementia,” they noted.
The study was funded by the National Institute on Aging, the National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Iowa State University, and the William S. Middleton Memorial Veterans Hospital. The investigators declared having no relevant conflicts of interest.