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. 2025 Jun:150:44-52.
doi: 10.1016/j.neurobiolaging.2025.03.002. Epub 2025 Mar 3.

White matter hyperintensities in dementia with lewy bodies and posterior cortical atrophy

Neha Singh-Reilly  1 , Nha Trang Thu Pham  2 , Jonathan Graff-Radford  1 , Mary M Machulda  3 , Anthony J Spychalla  2 , Matthew L Senjem  2 , Ronald C Petersen  1 , Val J Lowe  2 , Bradley F Boeve  1 , Clifford R Jack Jr  2 , Keith A Josephs  1 , Kejal Kantarci  2 , Jennifer L Whitwell  4
Affiliations

White matter hyperintensities in dementia with lewy bodies and posterior cortical atrophy

Neha Singh-Reilly et al. Neurobiol Aging. 2025 Jun.

Abstract

Dementia with Lewy bodies (DLB) and posterior cortical atrophy (PCA) are neurodegenerative disorders that can overlap clinically and in patterns of regional hypometabolism and show elevated white matter hyperintensity (WMH) burden. Little is known about the regional WMH burden in DLB patients without any interference of AD pathology and how these patterns compare to PCA patients. Twenty-two amyloid-negative DLB patients, 40 amyloid-positive PCA patients, and 49 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN. They underwent a 3 T head MRI, a Pittsburgh Compound B (PiB) PET scan, and a fluid-attenuated inversion recovery scan (FLAIR). The relationship between regional WMH volume and diagnosis was evaluated while adjusting for age and sex. DLB showed greater periventricular WMH burden in the temporal, occipital, and frontal lobes and greater WMH burden in the posterior corpus callosum compared to CU. PCA showed greater subcortical WMH burden in temporal, parietal, and occipital lobes, and greater periventricular WMH burden in the temporal, occipital, and frontal lobes, compared to CU. On comparing both dementia groups, PCA showed greater subcortical WMH burden in the temporal and occipital lobes compared to DLB, while DLB showed greater WMH burden in the posterior corpus callosum compared to PCA. Hence, DLB and PCA are both associated with periventricular WMHs, with deep subcortical WMHs being more characteristic of PCA, and callosal WMHs more characteristic of Aβ-negative DLB patients, suggesting different pathophysiological mechanisms underlying the development of WMHs in these two neurodegenerative diseases.

Keywords: Dementia with Lewy bodies; Posterior cortical atrophy; White matter hyperintensities.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jennifer L. Whitwell reports financial support was provided by National Institutes of Health. Kejal Kantarci reports financial support was provided by National Institutes of Health. Ronald C. Petersen reports financial support was provided by National Institutes of Health. Keith A. Josephs reports a relationship with National Institutes of Health that includes: funding grants. Mary M. Machulda reports a relationship with National Institutes of Health that includes: funding grants. Kejal Kantarci reports a relationship with National Institutes of Health that includes: funding grants. Jennifer L. Whitwell reports a relationship with National Institutes of Health that includes: funding grants. Jonathan Graff-Radford reports a relationship with National Institutes of Health that includes: funding grants. Matthew L. Senjem reports a relationship with Parexel International that includes: equity or stocks. Matthew L. Senjem reports a relationship with Gilead Sciences Inc that includes: equity or stocks. Matthew L. Senjem reports a relationship with Inovio Pharmaceuticals Inc that includes: equity or stocks. Matthew L. Senjem reports a relationship with Medtronic that includes: equity or stocks. Matthew L. Senjem reports a relationship with Oncothyreon Inc that includes: equity or stocks. Ronald C. Petersen reports a relationship with National Institutes of Health that includes: funding grants. Val J. Lowe reports a relationship with Bayer Schering Pharma AG that includes: consulting or advisory. Val J. Lowe reports a relationship with Eisai Inc that includes: consulting or advisory. Val J. Lowe reports a relationship with Avid Radiopharmaceuticals Inc that includes: consulting or advisory and funding grants. Val J. Lowe reports a relationship with Merck Research that includes: consulting or advisory. Val J. Lowe reports a relationship with GE Healthcare that includes: funding grants. Val J. Lowe reports a relationship with SIEMENS that includes: funding grants. Val J. Lowe reports a relationship with National Institutes of Health that includes: funding grants. Bradley F. Boeve reports a relationship with GE Healthcare that includes: consulting or advisory. Bradley F. Boeve reports a relationship with Myriad Genetics Inc that includes: funding grants. Bradley F. Boeve reports a relationship with National Institutes of Health that includes: funding grants. Bradley F. Boeve reports a relationship with Alzheimer’s Association that includes: funding grants. Clifford R. Jack reports a relationship with National Institutes of Health that includes: funding grants. Clifford R. Jack reports a relationship with GHR Foundation that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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