Ex vivo MRI transverse relaxation in community based older persons with and without Alzheimer's dementia.
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 R2alterations 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. R2was quantified using fast spin echo imaging. Voxelwise linear regression examined R2alterations between subjects diagnosed with AD dementia at death and those with no cognitive impairment. Voxels showing significant R2alterations were clustered into regions of interest (ROIs). Three R2profiles were compared, which were adjusted for (1) demographics only; (2) demographics and AD pathology; (3) demographics, AD pathology and other common neuropathologies. R2alterations 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, R2alterations identify AD dementia with improved accuracy, above and beyond demographics and neuropathologic indices (p<0.0001). In conclusion, R2alterations in AD dementia are not solely reflective of common age-related neuropathologies, suggesting that other mechanisms are at work.
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Lei
L
Yu
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, IL, USA.
Robert J
RJ
Dawe
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
Aron S
AS
Buchman
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA.
Patricia A
PA
Boyle
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Department of Pathology, Rush University Medical Center, Chicago, IL, USA.
Julie A
JA
Schneider
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
Konstantinos
K
Arfanakis
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA. Electronic address: David_A_Bennett@Rush.edu.
David A
DA
Bennett
D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D001344:Autopsy; D001921:Brain / Q000000981:diagnostic imaging*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D012372:ROC Curve; D066127:White Matter / Q000000981:diagnostic imaging
AD dementia; Age-related neuropathology; Ex vivo MRI; Transverse relaxation alterations