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Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease.

Abstract：

IMPORTANCE:Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET). OBJECTIVES:To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicted variation in regional glucose metabolism is associated with worse cognitive performance. DESIGN, SETTING, AND PARTICIPANTS:This population-based, cross-sectional study included 150 cognitively normal, late middle-aged (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for Alzheimer's Prevention (WRAP) study, a general community sample enriched for AD parental history. Participants underwent cognitive testing, fasting blood draw, and FDG-PET at baseline. We used the homeostatic model assessment of peripheral insulin resistance (HOMA-IR). Regression analysis tested the statistical effect of HOMA-IR on global glucose metabolism. We used a voxelwise analysis to determine whether HOMA-IR predicted regional glucose metabolism. Finally, predicted variation in regional glucose metabolism was regressed against cognitive factors. Covariates included age, sex, body mass index, apolipoprotein E ε4 genotype, AD parental history status, and a reference region used to normalize regional uptake. MAIN OUTCOMES AND MEASURES:Regional glucose uptake determined using FDG-PET and neuropsychological factors. RESULTS:Higher HOMA-IR was associated with lower global glucose metabolism (β = -0.29; P < .01) and lower regional glucose metabolism across large portions of the frontal, lateral parietal, lateral temporal, and medial temporal lobes (P < .05, familywise error corrected). The association was especially robust in the left medial temporal lobe (R2 = 0.178). Lower glucose metabolism in the left medial temporal lobe predicted by HOMA-IR was significantly related to worse performance on the immediate memory (β = 0.317; t148 = 4.08; P < .001) and delayed memory (β = 0.305; t148 = 3.895; P < .001) factor scores. CONCLUSIONS AND RELEVANCE:Our results show that insulin resistance, a prevalent and increasingly common condition in developed countries, is associated with significantly lower regional cerebral glucose metabolism, which in turn may predict worse memory performance. Midlife may be a critical period for initiating treatments to lower peripheral insulin resistance to maintain neural metabolism and cognitive function.

journal_name

JAMA Neurol

journal_title

JAMA neurology

authors

Willette AA,Bendlin BB,Starks EJ,Birdsill AC,Johnson SC,Christian BT,Okonkwo OC,La Rue A,Hermann BP,Koscik RL,Jonaitis EM,Sager MA,Asthana S

doi

10.1001/jamaneurol.2015.0613

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

1013-20

issue

eissn

2168-6149

issn

2168-6157

pii

2398420

journal_volume

pub_type

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Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease.