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Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer's dementia.

ABSTRACT: Alterations of the transverse relaxation rate, R2, measured using MRI, are observed in older persons with Alzheimer's (AD) dementia. However, the spatial pattern of these alterations and the degree to which they reflect the accumulation of common age-related neuropathologies are unknown. In this study, we characterized the profile of R2 alterations in post-mortem brains of persons with clinical diagnosis of AD dementia and investigated how the profile differs after accounting for neuropathologic indices of AD, cerebral infarcts, Lewy body disease, hippocampal sclerosis and transactive response DNA-binding protein 43. Data came from 567 post-mortem brains donated by participants in two cohort studies of aging and dementia. R2 was quantified using fast spin echo imaging. Voxelwise linear regression examined R2 alterations between subjects diagnosed with AD dementia at death and those with no cognitive impairment. Voxels showing significant R2 alterations were clustered into regions of interest (ROIs). Three R2 profiles were compared, which were adjusted for (1) demographics only; (2) demographics and AD pathology; (3) demographics, AD pathology and other common neuropathologies. R2 alterations were observed throughout the hemisphere, most commonly in white matter. Of the distinct ROIs identified, the largest region encompassed large portions of white matter in all lobes. This ROI became smaller in size but remained largely intact after adjusting for AD and other neuropathologic indices. Further, R2 alterations identify AD dementia with improved accuracy, above and beyond demographics and neuropathologic indices (p<0.0001). In conclusion, R2 alterations in AD dementia are not solely reflective of common age-related neuropathologies, suggesting that other mechanisms are at work.

SUBMITTER: Yu L

PROVIDER: S-EPMC5325779 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer's dementia.

Yu Lei L Dawe Robert J RJ Buchman Aron S AS Boyle Patricia A PA Schneider Julie A JA Arfanakis Konstantinos K Bennett David A DA

Behavioural brain research 20160903 Pt B

Alterations of the transverse relaxation rate, R<sub>2</sub>, measured using MRI, are observed in older persons with Alzheimer's (AD) dementia. However, the spatial pattern of these alterations and the degree to which they reflect the accumulation of common age-related neuropathologies are unknown. In this study, we characterized the profile of R<sub>2</sub> alterations in post-mortem brains of persons with clinical diagnosis of AD dementia and investigated how the profile differs after accounti ...[more]

PMID: 27596378

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Project description:BackgroundNeuropsychiatric symptoms (NPS) have been reported to be useful in predicting incident dementia among cognitively normal older persons. However, the literature has not been conclusive on the differential utilities of the various NPS in predicting the subtypes of dementia. This study compared the risks of Alzheimer's and non-Alzheimer's dementia associated with the various NPS, among cognitively normal older persons.MethodsThis cohort study included 12,452 participants from the Alzheimer's Disease Centers across USA, who were ≥ 60 years and had normal cognition at baseline. Participants completed the Neuropsychiatric Inventory-Questionnaire at baseline and were followed up almost annually for incident dementia (median follow-up = 4.7 years). Symptom clusters of NPS-as identified from exploratory and confirmatory factor-analyses-were included in the Cox regression to investigate their associations with incident dementia.ResultsThe various NPS showed independent yet differential associations with incident dementia. Although psychotic symptoms were rarely endorsed by the participants, they predicted much higher risk of dementia (HR 3.6, 95% CI 2.0-6.4) than affective symptoms (HR 1.5, 95% CI 1.2-1.8) or agitation symptoms (HR 1.6, 95% CI 1.3-2.1). Psychotic symptoms predicted all dementia subtypes, while affective and agitation symptoms differentially predicted some subtypes. Across dementia subtypes, psychotic symptoms had relatively higher risk estimates than affective or agitation symptoms, with the risk estimates being particularly high in non-Alzheimer's dementia.ConclusionsAmong cognitively normal individuals, the presence of NPS may warrant greater clinical vigilance as precursors to dementia and its subtypes. The findings highlight the need for further research to enrich our understanding on the neurobiological links between various NPS and dementia subtypes. They may also change the clinical approach in managing late-life psychotic symptoms, requiring a greater emphasis on dementia surveillance in the diagnostic criteria of late-life psychotic disorders.

Dataset Information

Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer's dementia.

Publications

Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer's dementia.

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