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Associations between mean apparent propagator MRI and cerebrospinal fluid markers of AD pathology, neurodegeneration, and glial activation, in cognitively unimpaired adults
Author(s) -
Moody Jason F.,
Dean Douglas C.,
Kecskemeti Steven R.,
Blennow Kaj,
Zetterberg Henrik,
Carlsson Cynthia M.,
Johnson Sterling C.,
Alexander Andrew L.,
Bendlin Barbara B.
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.053320
Subject(s) - diffusion mri , cerebrospinal fluid , pathology , white matter , putamen , neurodegeneration , medicine , fractional anisotropy , atrophy , neuroscience , magnetic resonance imaging , nuclear medicine , psychology , disease , radiology
Background Numerous studies have reported correlations between diffusion tensor imaging (DTI) metrics and cerebrospinal (CSF) biomarkers of Alzheimer’s disease (AD) pathology. However, the assumption of Gaussian diffusion in DTI limits the ability to characterize white matter (WM) microstructural changes. Mean apparent propagator (MAP) MRI is a model that attempts to overcome this limitation by allowing for the estimation of parameters that convey more precise information about WM microstructure. To investigate MAP MRI’s sensitivity to early WM degeneration associated with preclinical, asymptomatic AD pathology, we examined the relationship between CSF biomarkers and MAP MRI microstructural parameters in 92 cognitively unimpaired adults. Method 92 cognitively unimpaired controls from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center were imaged with multi‐shell diffusion‐weighted MRI. DTI metrics (FA, MD, RD, AxD) were computed and the MAP MRI model was employed to calculate various microstructural parameters: Return to origin probability (RTOP), return to axis probability (RTAP), return to plane probability (RTPP), mean squared displacement (MSD), Non‐Gaussianity (NG), and q‐space inverse variance (QIV). DTI and MAP parameter values were extracted from the cingulum and correlated to Aβ 42 , P‐Tau, P‐Tau/Aβ 42 , YKL‐40, and neurofilament light chain (NFL) levels in lumbar cerebrospinal fluid samples. Result MAP parameters were moderately and significantly correlated to most CSF measures. RTPP was significantly correlated to all 5 CSF measures, while MSD, NG, and QIV were significantly correlated to 4 of 5 CSF measures. NFL, a known marker for axonal degeneration, was significantly related to 5 of the 6 MAP parameters assessed. Meanwhile, correlations between DTI and CSF measures were weak and non‐significant. Conclusion These preliminary results highlight the potential of MAP MRI to detect early WM deterioration indicative of preclinical, asymptomatic AD and associated neurodegeneration. MAP metrics extracted from a commonly affected WM tract in AD were more strongly and significantly correlated with CSF measures than DTI metrics were, suggesting that MAP MRI may be more useful than DTI for identifying the earliest WM microstructural changes associated with AD. Future work will incorporate longitudinal data and assess the effects of CSF and molecular imaging markers on MAP age trajectories.