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Insulin resistance in late middle-aged patients affected risk for Alzheimer’s disease
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Recent data suggest that insulin resistance among late middle-aged patients is associated with progressive atrophy in regions of the brain affected by early Alzheimer’s disease. Additionally, insulin resistance in this patient population may negatively affect gray matter volume in the medial temporal lobe.
“Most studies to date have found that measures of insulin resistance correspond to lower hippocampal volume either cross-sectionally or longitudinally. In our sample, this association was predominantly found in anterior hippocampus abutting the amygdala and parahippocampus,” the researchers wrote. “This result is important because morphological changes in entorhinal cortex and anterior hippocampus, particularly the cornu ammonis fields, are sensitive to mild cognitive impairment and early Alzheimer’s disease relative to normative aging.”
Auriel A. Willette, PhD, of the Geriatric Research Education and Clinical Center at William S. Middleton Memorial Veterans Hospital, the Waisman Laboratory for Brain Imaging and Behavior at the University of Wisconsin-Madison, and the Wisconsin Alzheimer’s Disease Research Center in Madison, and colleagues assessed 372 late middle-aged, asymptomatic patients (mean age 57.66 years). The patients were part of the Wisconsin Registry for Alzheimer’s Prevention (WRAP) ongoing study.
Researchers collected basal glucose and insulin, apolipoprotein E genotype, family history and Rey Auditory Verbal Learning Test (RAVLT) scores. Additional tests included voxel-based morphometry and tensor-based morphometry to examine the link between insulin resistance with baseline brain volume and progressive gray matter atrophy. Four years after baseline, a subset of 121 patients underwent follow-up volumetric brain scans.
Willette and colleagues found that higher insulin resistance predicted less gray matter at baseline and at the 4-year follow-up in the medial temporal lobe, prefrontal cortices, precuneus and other parietal gyri.
“Across all 372 participants, higher [homeostasis model assessment of insulin resistance] was significantly associated with less gray matter at baseline in several regions implicated in early Alzheimer’s disease,” the researchers wrote.
According to data from the region-of-interest analyses, higher insulin resistance was associated with medial temporal lobe atrophy.
The researchers said the link between HOMA-IR, the chosen region of interest, including hippocampus and parahippocampus, and RAVLT scores were “modest but consistent.”
Despite these findings, Willette and colleagues wrote that causal inferences should not be made based upon the associations.
Disclosure: The researchers report no relevant financial disclosures.
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