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P2–172: Evaluation of amyloid‐based enrichment using established and novel clinical instruments
Author(s) -
Yu Peng,
Martenyi Ferenc,
Sun Jia,
Siemers Eric,
Schwarz Adam,
Sims John
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.05.817
Subject(s) - nuclear medicine , posterior cingulate , sample size determination , medicine , standardized uptake value , amyloid (mycology) , positron emission tomography , cortex (anatomy) , psychology , pathology , neuroscience , mathematics , statistics
Background: Converging evidence suggests that Alzheimer’s disease (AD) involves impairments in insulin signaling. Diabetics are at increased risk for AD, brain insulin levels are decreased in AD, and both AD patients and people at risk for AD show metabolic deficits as indexed by F18-fluorodeoxyglucose positron emission tomography (FDG-PET). While midlife may be a critical period to initiate intervention treatments against AD, the extent to which insulin resistance in midlife is associated with brain alterations remains incompletely characterized. In this study, we assessed the impact of insulin resistance on neural metabolic function in cognitively healthy, late middle-aged adults. Methods: Participants (n1⁄4150, mean age1⁄460.7 yrs, SD 1⁄4 5.8) from the Wisconsin Registry for Alzheimer’s Prevention underwent cognitive testing, fasting blood draw, and FDG-PET. HOMA-IR was calculated as [basal glucose(mg/dL)*basal insulin(mU/mL)/405]. Regression analysis was used to test the effect of HOMA-IR on global FDG-PETuptake (normalized to occipital cortex). Avoxel-wise multiple regression analysis was used to test for a regional effect of HOMA-IR on FDG-PET uptake. Analyses controlled for age, sex, APOE4 genotype, and parental family history of AD. Results: Insulin resistance (indexed by higher HOMA-IR) was associated with lower global FDG-PET uptake and regional reductions across large portions of frontal, lateral parietal, lateral temporal, and medial temporal lobe (p<.001, Figure 1). After correcting for multiple comparisons, reduced FDG-PET uptake was localized to left parahippocampal gyrus (p<.05 FWE, Figure 2). FDG-PET signal extracted from the left parahippocampal gyrus was associated with cognitive function, where lower uptake was associated with lower performance on tests of verbal and immediate memory. Conclusions: Our results concur with previous studies which suggest that insulin resistance is associated with alterations in brain metabolism. This study is the first to examine the