Dataset Information

FMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease.

ABSTRACT: To determine whether APOE genotype influences brain response and whether nonverbal stimuli generate findings comparable with those of previous studies that used verbal stimuli. The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults.Twenty nondemented participants with normal episodic memory function were divided into two groups based on the presence (n = 10) or absence (n = 10) of the APOE epsilon4 allele. Picture learning was completed during functional MRI in a blocked design alternating between experimental (novel pictures) and control (repeated picture) conditions.Nondemented older adults with an APOE epsilon4 allele showed greater magnitude and extent of BOLD brain response during learning of new pictures relative to their matched epsilon3 counterparts. Different patterns and directions of association between hippocampal activity and learning and memory performance were also demonstrated.The results suggest that brain response differences are not due to poorer general memory abilities, differential atrophy, or brain response during control conditions, but instead appear to be directly influenced by APOE genotype. Results are consistent with a compensatory hypothesis wherein older adults at genetic risk for Alzheimer disease by virtue of the APOE epsilon4 allele appear to require additional cognitive effort to achieve comparable performance levels on tests of episodic memory encoding.

SUBMITTER: Bondi MW

PROVIDER: S-EPMC1761695 | biostudies-literature | 2005 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease.

Bondi Mark W MW Houston Wes S WS Eyler Lisa T LT Brown Gregory G GG

Neurology 20050201 3

<h4>Objective</h4>To determine whether APOE genotype influences brain response and whether nonverbal stimuli generate findings comparable with those of previous studies that used verbal stimuli. The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults.<h4>Methods</h4>Twenty nondemented participants with normal episodic memory function were divided into two groups based on the presenc ...[more]

PMID: 15699382

Similar Datasets

Project description:Background and objectivesBrain amyloid deposition, a major risk factor for Alzheimer's disease (AD), is currently estimated by measuring cerebrospinal fluid or plasma amyloid peptide levels, or by positron-emission tomography imaging. Assessing genetic risks relating to amyloid deposition before any accumulation has occurred would allow for earlier intervention in persons at increased risk for developing AD. Previous work linking amyloid burden and genetic risk relied almost exclusively on APOE, a major AD genetic risk factor. Here, we ask whether a polygenic risk score (PRS) that incorporates an optimized list of common variants linked to AD and excludes APOE is associated with brain amyloid load in cognitively unimpaired elderly adults.MethodsWe included 291 elderly asymptomatic participants from the INveStIGation of AlzHeimer's PredicTors (INSIGHT-preAD) cohort who underwent amyloid imaging, including 83 amyloid-positive (+) participants. We used an Alzheimer's (A) PRS composed of 33 AD risk variants excluding APOE, and selected the 17 variants that showed the strongest association with amyloid positivity to define an optimized (oA) PRS. Participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study [228 participants, 90 amyloid (+)] were tested as a validation cohort. Finally, 2,300 AD patients and 6,994 controls from the European Alzheimer's Disease Initiative (EADI) were evaluated.ResultsA-PRS was not significantly associated with amyloid burden in the INSIGHT or ADNI cohorts with or without correction for APOE genotype. However, oA-PRS was significantly associated with amyloid status independently of APOE adjustment (INSIGHT OR: 5.26 [1.71-16.88]; ADNI OR: 3.38 [1.02-11.63]). Interestingly, oA-PRS accurately discriminated amyloid (+) and (-) APOE ε4 carriers (INSIGHT OR: 181.6 [7.53-10,674.6]; ADNI OR: 44.94 [3.03-1,277]). A-PRS and oA-PRS showed a significant association with disease status in the EADI cohort (OR: 1.68 [1.53-1.85] and 2.06 [1.73-2.45] respectively). Genes assigned to oA-PRS variants were enriched in ontologies related to Aβ metabolism and deposition.DiscussionPRSs relying on AD genetic risk factors excluding APOE may improve risk prediction for brain amyloid, allowing stratification of cognitively unimpaired individuals at risk of AD independent of their APOE status.

Project description:ObjectivesTo measure the burden of delirium in older adults with or without Alzheimer disease or related disorders (ADRDs).DesignProspective, observational cohort.SettingInpatient hospital and study participants' homes.ParticipantsA subset (n = 267) of older medical and surgical patients and their caregivers enrolled in the Better Assessment of Illness study.MeasurementsDelirium burden was measured using the DEL-B instrument (range = 0-40, with higher scores indicating greater burden) in caregivers (DEL-B-C) and patients 1 month after hospitalization. Severity of cognitive impairment (Montreal Cognitive Assessment [MoCA]), delirium presence (Confusion Assessment Method [CAM]), and delirium severity (CAM-Severity [CAM-S]) were measured during hospitalization and at 1-month follow-up. ADRD diagnosis was determined by a clinical consensus process.ResultsFor patients with (n = 56) and without (n = 211) ADRD, both DEL-B instruments had good internal consistency. DEL-B-C scores had a median (interquartile range) among caregivers of patients with and without ADRD of 9 (5-15) and 5 (1-11), respectively (P < .05). If the patient developed delirium, caregivers experienced greater burden (β[delirium × ADRD] = -.29; P = .42), regardless of ADRD status. Further, caregiver burden was modestly correlated with patient MoCA scores (Spearman correlation coefficient, ρ = -0.18; P = .01). Patients with ADRD who developed delirium self-reported less burden than those without ADRD (β[delirium × ADRD] = -.67; P = .044). As with caregivers, delirium burden was modestly correlated with patient MoCA score (ρ = -0.18; P = .005) and correlated with the CAM-S in patients without ADRD (ρ = 0.38; P < .001) but not for patients with ADRD (ρ = -0.07; P = .61).ConclusionsDelirium resulted in the same degree of increased caregiver burden regardless of whether a patient had ADRD, signifying delirium is equally stressful to caregivers, even among those with experience caring for someone with a chronic cognitive disorder. Delirium burden is only modestly associated with degree of cognitive impairment, suggesting that other aspects of delirium contribute to burden. J Am Geriatr Soc 67:2587-2592, 2019.

Project description:ImportancePreclinical studies suggest that amylin has a U-shaped dose-response association with risk of Alzheimer disease (AD). The association of plasma amylin with AD in humans is unknown.ObjectivesTo measure amylin concentration in plasma by using enzyme-linked immunosorbent assay and to study the association between plasma amylin, incidence of AD, and brain structure in humans.Design, setting, and participantsThis cohort study used data from the Framingham Heart Study offspring cohort from 1998 to 2015. Using a Monte Carlo approach, participants were divided into 3 plasma amylin concentration groups: (1) low (<75 pmol/L), (2) high (75-2800 pmol/L), and (3) extremely high (≥2800 pmol/L). Data analyses were conducted October 5, 2017, to December 18, 2018.ExposuresBaseline plasma amylin concentrations at examination 7.Main outcomes and measuresIncidence of dementia or AD and brain volumetric measures from structural magnetic resonance imaging data.ResultsFrom the Framingham Heart Study offspring cohort, 3061 participants (mean [SD] age at baseline, 61.0 [9.5] years; 1653 [54.0%] women) who had plasma amylin measurements, dementia incidence, and brain volume measurements on record were included in this study. The distribution of plasma amylin concentrations was highly skewed (median [interquartile range], 7.5 [4.6-18.9] pmol/L; mean [SD], 302.3 [1941.0] pmol/L; range, 0.03-44 623.7 pmol/L). Compared with the low plasma amylin concentration group, the high plasma amylin concentration group had a lower rate of AD incidence (2.3% vs 5.6%; P = .04), but the extremely high plasma amylin concentration group had a higher rate of AD incidence (14.3%; P < .001). After adjusting for age, sex, education, body mass index, diabetes, cardiovascular disease, high-density lipoprotein level, and APOE4, high plasma amylin was not associated with decreased AD risk (hazard ratio, 0.42 [95% CI, 0.16-1.14]; P = .09) but was positively associated with volume of gray matter in the temporal lobe (β = 0.17 [SE, 0.05]; P < .001). In contrast, extremely high plasma amylin concentration was associated with a higher AD risk (hazard ratio, 2.51 [95% CI, 1.38-4.57]; P = .003) but not associated with temporal lobe volume (β = 0.02 [SE, 0.07]; P = .82).Conclusions and relevanceThis study found that plasma amylin concentration was associated with AD incidence and brain structure with a U-shaped pattern. These findings are consistent with preclinical findings that suggest amylin is a neuropeptide that is physiological; however, at extremely high concentrations, it may lead to amylin aggregation and therefore may be a risk factor for AD.

Dataset Information

FMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease.

Publications

fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets