Barbara B. Bendlin, PhD – Slide of the Week

Barbara B. Bendlin, PhD - Slide of the Week

Title: MAP-MRI shows that Alzheimer’s disease is associated with widespread white matter injury

Legend: White matter skeleton voxels with significant associations between Alzheimer’s disease pathology as measured in CSF (top panel: Aβ42/40, bottom panel: pTau) and DWI Metrics (MAP‐MRI: Red, NODDI: Blue, DTI: None) overlaid on the 1 mm MNI 152 standard T1 template. White matter is delineated by the mean FA skeleton of all subjects (green). Techniques such as NODDI and MAP-MRI are sensitive to neural injury in Alzheimer’s disease. Results are corrected for age, sex, and multiple comparisons across voxels with p < 0.05.

Citation: Moody JF, Dean DC 3rd, Kecskemeti SR, Blennow K, Zetterberg H, Kollmorgen G, Suridjan I, Wild N, Carlsson CM, Johnson SC, Alexander AL, Bendlin BB. Associations between diffusion MRI microstructure and cerebrospinal fluid markers of Alzheimer’s disease pathology and neurodegeneration along the Alzheimer’s disease continuum. Alzheimers Dement (Amst). 2022 Dec 4;14(1):e12381. doi: 10.1002/dad2.12381. PMID: 36479018; PMCID: PMC9720004.


White matter (WM) degeneration is a critical component of early Alzheimer’s disease (AD) pathophysiology. Diffusion‐weighted imaging (DWI) models, including diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and mean apparent propagator MRI (MAP‐MRI), have the potential to identify early neurodegenerative WM changes associated with AD.

Methods – We imaged 213 (198 cognitively unimpaired) aging adults with DWI and used tract‐based spatial statistics to compare 15 DWI metrics of WM microstructure to 9 cerebrospinal fluid (CSF) markers of AD pathology and neurodegeneration treated as continuous variables.

Results – We found widespread WM injury in AD, as indexed by robust associations between DWI metrics and CSF biomarkers. MAP‐MRI had more spatially diffuse relationships with Aβ42/40 and pTau, compared with NODDI and DTI.

Discussion – Our results suggest that WM degeneration may be more pervasive in AD than is commonly appreciated and that innovative DWI models such as MAP‐MRI may provide clinically viable biomarkers of AD‐related neurodegeneration in the earliest stages of AD progression.

About the Lab: The mission of the Bendlin Lab is to take a multidisciplinary, collaborative, and inclusive approach to understand the factors that contribute to healthy and pathological brain aging. As a part of the Wisconsin Alzheimer’s Disease Research Center, we share the goal of improving the lives of those affected by Alzheimer’s disease. The Bendlin Lab strives to foster a non-discriminatory, diverse, and inclusive research and academic environment. Our research projects, supported by multiple NIA/NIH grants, donors, and private funding agencies, study brain structure and function in midlife and in older adults using a wide array of neuroimaging, biomarker, and genomic analyses. With a focus on education and outreach, the Bendlin Lab engages with students, staff, participants, and individuals in the community to promote greater awareness and understanding of Alzheimer’s disease.

Investigator: Barbara B. Bendlin, PhD

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