Dataset Information

Insulin resistance, brain atrophy, and cognitive performance in late middle-aged adults.

ABSTRACT: Insulin resistance dysregulates glucose uptake and other functions in brain areas affected by Alzheimer disease. Insulin resistance may play a role in Alzheimer disease etiopathogenesis. This longitudinal study examined whether insulin resistance among late middle-aged, cognitively healthy individuals was associated with 1) less gray matter in Alzheimer disease-sensitive brain regions and 2) worse cognitive performance.Homeostasis model assessment of insulin resistance, gray matter volume, and the Rey Auditory Verbal Learning Test (RAVLT) were acquired in 372 participants at baseline and a consecutive subset of 121 individuals ~4 years later. Voxel-based morphometry and tensor-based morphometry were used, respectively, to test the association of insulin resistance with baseline brain volume and progressive gray matter atrophy.Higher insulin resistance predicted less gray matter at baseline and 4 years later in medial temporal lobe, prefrontal cortices, precuneus, and other parietal gyri. A region-of-interest analysis, independent of the voxel-wise analyses, confirmed that higher insulin resistance was related to medial temporal lobe atrophy. Atrophy itself corresponded to cognitive deficits in the RAVLT. Temporal lobe atrophy that was predicted by higher insulin resistance significantly mediated worse RAVLT encoding performance.These results suggest that insulin resistance in an asymptomatic, late middle-aged cohort is associated with progressive atrophy in regions affected by early Alzheimer disease. Insulin resistance may also affect the ability to encode episodic information by negatively influencing gray matter volume in medial temporal lobe.

SUBMITTER: Willette AA

PROVIDER: S-EPMC3554303 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Insulin resistance, brain atrophy, and cognitive performance in late middle-aged adults.

Willette Auriel A AA Xu Guofan G Johnson Sterling C SC Birdsill Alex C AC Jonaitis Erin M EM Sager Mark A MA Hermann Bruce P BP La Rue Asenath A Asthana Sanjay S Bendlin Barbara B BB

Diabetes care 20121015 2

<h4>Objective</h4>Insulin resistance dysregulates glucose uptake and other functions in brain areas affected by Alzheimer disease. Insulin resistance may play a role in Alzheimer disease etiopathogenesis. This longitudinal study examined whether insulin resistance among late middle-aged, cognitively healthy individuals was associated with 1) less gray matter in Alzheimer disease-sensitive brain regions and 2) worse cognitive performance.<h4>Research design and methods</h4>Homeostasis model asses ...[more]

PMID: 23069842

Similar Datasets

Project description: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 ?4 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 (??=?-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 (??=?0.317; t148?=?4.08; P?<?.001) and delayed memory (??=?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.

Project description:ObjectivesStudies of autosomal dominant Alzheimer disease (AD) have shown structural and cognitive changes in mutation carriers decades prior to clinical disease. Whether such changes are detectable in offspring of persons with sporadic dementia remains unknown. We related prospectively verified parental dementia to brain MRI and cognitive testing in the offspring, within a 2-generational community-based cohort.MethodsA total of 717 Framingham offspring (mean age: 59 +/- 8 years) were studied. In multivariate analyses, we compared offspring with and without verified parental dementia (and AD) for 1) performance on tests of memory, abstract reasoning, and cognitive flexibility, and 2) volumetric brain MRI measures of total cerebral brain volume (TCBV), hippocampal volume (HV), and white matter hyperintensity volume (WMHV), assessed cross-sectionally and longitudinally.ResultsWhen testing the association of parental dementia and AD with baseline cognitive performance, we observed an interaction of parental dementia and AD with APOE epsilon4 status (p < 0.002). In APOE epsilon4 carriers only (n = 165), parental dementia was associated with poorer scores on tests of verbal memory (beta = -1.81 +/- 0.53, p < 0.001) and visuospatial memory (beta = -1.73 +/- 0.47, p < 0.001). These associations were stronger for parental AD (beta = -1.97 +/- 0.52, p < 0.001, beta = -1.95 +/- 0.48, p < 0.001), equivalent to 14-16 years of brain aging. Among APOE epsilon4 carriers, offspring of participants with dementia were also more likely to show an annual decline in TCBV in the top quartile (odds ratio = 4.67 [1.26-17.30], p = 0.02). Regardless of APOE epsilon4 status, participants with parental dementia were more likely to be in the highest quartile of decline in executive function test scores (odds ratio = 1.61 [1.02-2.53], p = 0.04).ConclusionsAmong middle-aged carriers of the APOE epsilon4 allele, parental dementia and Alzheimer disease were associated with poorer verbal and visuospatial memory and a higher rate of global brain atrophy.

Project description:BackgroundDaily activities have been associated with neurocognitive performance. However, much of this research has used in-person neuropsychological testing that requires participants to travel to a laboratory or clinic, which may not always be feasible and does not allow for the examination of real-time relationships between cognition and behavior. Thus, there is a need to understand the real-time relationship between activities in the real world and neurocognitive functioning to improve tracking of symptoms or disease states and aid in the early identification of neurocognitive deficits among at-risk individuals.ObjectiveWe used a smartphone-based ecological momentary cognitive assessment (EMCA) platform to examine real-time relationships between daily activities and neurocognitive performance (executive functioning and verbal learning) in the everyday environment of middle-aged and older adults with and without HIV.MethodsA total of 103 adults aged 50-74 years (67 persons with HIV; mean age 59 years, SD 6.4) were recruited from the University of California, San Diego HIV Neurobehavioral Research Program and the San Diego community. Participants completed our EMCA protocol for 14 days. Participants reported their current daily activities 4 times per day; following 2 of the 4 daily ecological momentary assessment (EMA) surveys, participants were administered the mobile Color-Word Interference Test (mCWIT) and mobile Verbal Learning Test (mVLT), each once per day. Activities were categorized into cognitively stimulating activities, passive leisure activities, and instrumental activities of daily living (IADLs). We used multilevel modeling to examine the same-survey and lagged within-person and between-person effects of each activity type on mobile cognitive performance.ResultsOn average, participants completed 91% of the EMA surveys, 85% of the mCWIT trials, and 80% of the mVLT trials, and they reported engaging in cognitively stimulating activities on 17% of surveys, passive leisure activities on 33% of surveys, and IADLs on 20% of surveys. Adherence and activity percentages did not differ by HIV status. Within-persons, engagement in cognitively stimulating activities was associated with better mCWIT performance (β=-1.12; P=.007), whereas engagement in passive leisure activities was associated with worse mCWIT performance (β=.94; P=.005). There were no lagged associations. At the aggregate between-person level, a greater percentage of time spent in cognitively stimulating activities was associated with better mean mVLT performance (β=.07; P=.02), whereas a greater percentage of time spent in passive leisure activities was associated with worse mean mVLT performance (β=-.07; P=.01). IADLs were not associated with mCWIT or mVLT performance.ConclusionsSmartphones present unique opportunities for assessing neurocognitive performance and behavior in middle-aged and older adults' own environment. Measurement of cognition and daily functioning outside of clinical settings may generate novel insights on the dynamic association of daily behaviors and neurocognitive performance and may add new dimensions to understanding the complexity of human behavior.

Dataset Information

Insulin resistance, brain atrophy, and cognitive performance in late middle-aged adults.

Publications

Insulin resistance, brain atrophy, and cognitive performance in late middle-aged adults.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets