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Altered fMRI activation during mental rotation in those at genetic risk for Alzheimer disease.

ABSTRACT: This study was undertaken to examine differential functional MRI patterns in those at genetic risk for Alzheimer disease (AD), specifically investigating parietal lobe activation, a brain region with changes noted in the early stages of AD.This study uses functional MRI to investigate blood oxygenation level dependent changes in the parietal lobe in a high-risk sample of 18 asymptomatic offspring of autopsy-confirmed AD cases, compared to 15 matched controls. The cognitive activation paradigm was a mental rotation task, which requires individuals to rotate three-dimensional cube stimuli to judge their similarity.We found no differences in either reaction time or performance accuracy between groups. However, the at-risk individuals showed increases in activation in the right superior parietal lobule (BA 7), the right insula (BA 13), the right middle frontal gyrus (BA 10), and the right inferior frontal gyrus (BA 47).We present evidence for a compensatory mechanism for those at increased risk for Alzheimer disease (AD). This study examines and confirms parietal changes with increased risk for late-onset AD, despite normal cognitive performance. Added to the previous findings from this group, these results demonstrate the sensitivity of functional imaging measures to brain changes that are not yet reflected in cognitive performance, which may ultimately serve as an important indicator of disease.

SUBMITTER: Yassa MA

PROVIDER: S-EPMC2671804 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Altered fMRI activation during mental rotation in those at genetic risk for Alzheimer disease.

Yassa Michael A MA Verduzco Guillermo G Cristinzio Catherine C Bassett Susan Spear SS

Neurology 20080501 20

<h4>Objective</h4>This study was undertaken to examine differential functional MRI patterns in those at genetic risk for Alzheimer disease (AD), specifically investigating parietal lobe activation, a brain region with changes noted in the early stages of AD.<h4>Methods</h4>This study uses functional MRI to investigate blood oxygenation level dependent changes in the parietal lobe in a high-risk sample of 18 asymptomatic offspring of autopsy-confirmed AD cases, compared to 15 matched controls. Th ...[more]

PMID: 18474845

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Project description:BackgroundIncreasing use of genetic testing raises questions about disclosing secondary findings, including pleiotropic information.ObjectiveTo determine the safety and behavioral effect of disclosing modest associations between apolipoprotein E (APOE) genotype and coronary artery disease (CAD) risk during APOE-based genetic risk assessments for Alzheimer disease (AD).DesignRandomized, multicenter equivalence clinical trial. (ClinicalTrials.gov: NCT00462917).Setting4 teaching hospitals.Participants257 asymptomatic adults were enrolled, 69% of whom had 1 AD-affected first-degree relative.InterventionDisclosure of genetic risk information about AD and CAD (AD+CAD) or AD only (AD-only).MeasurementsPrimary outcomes were Beck Anxiety Inventory (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores at 12 months. Secondary outcomes were all measures at 6 weeks and 6 months and test-related distress and health behavior changes at 12 months.ResultsAt 12 months, mean BAI scores were 3.5 in both the AD-only and AD+CAD groups (difference, 0.0 [95% CI, -1.0 to 1.0]), and mean CES-D scores were 6.4 and 7.1 in the AD-only and AD+CAD groups, respectively (difference, 0.7 [CI, -1.0 to 2.4]). Both confidence bounds fell within the equivalence margin of ±5 points. Among carriers of the APOE ε4 allele, distress was lower in the AD+CAD groups (difference, -4.8 [CI, -8.6 to -1.0]) (P = 0.031 for the interaction between group and APOE genotype). Participants in the AD+CAD groups also reported more health behavior changes, regardless of APOE genotype.LimitationsOutcomes were self-reported by volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomly assigned participants.ConclusionDisclosure of pleiotropic information did not increase anxiety or depression and may have decreased distress among persons at increased risk for 2 conditions. Providing risk modification information about CAD improved health behaviors. Findings highlight the potential benefits of disclosure of secondary genetic findings when options exist for decreasing risk.Primary funding sourceNational Human Genome Research Institute.

Dataset Information

Altered fMRI activation during mental rotation in those at genetic risk for Alzheimer disease.

Publications

Altered fMRI activation during mental rotation in those at genetic risk for Alzheimer disease.

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