Objective: This study aimed to compare white matter hyperintensity (WMH) burden between PSP and PD using a novel AI-based tool for more accurate WMH volume quantification.

Background: Small vessel disease (SVD)is found in up to 65% of PSP patients at autopsy[1] and hypertension (HTN) is a debated risk factor for the disease[2][3]. Ghika et al. reported higher presymptomatic HTN rates in PSP than in other parkinsonian disorders, suggesting early adrenergic nucleus degeneration may explain both HTN and SVD[4]. SVD has been linked to tau phosphorylation[5][6], and tau accumulation can worsen SVD[7]. Additionally, SVD may impair glymphatic clearance of tau and beta-amyloid, promoting tau propagation[6].

Method: We retrospectively reviewed two age- and sex-matched cohorts: 67 PSP (mean age 70.5) and 67 PD (mean age 70.7). MRI was performed using 1.5T and 3T scanners to acquire 3D T1w (1mm isotropic) and 2D FLAIR (0.43×0.43×5.0mm) per institutional protocols. T1w and FLAIR images were co-registered using rigid body registration, and WMH volumes were quantified with a novel CNN-based tool[8] optimized for diverse clinical datasets. Volumes were adjusted for intracranial volume (ICV) and log10 normalized. Primary analysis used linear regression to compare WMHvol/ICV between PSP and PD, accounting for age, sex, MR field strength, and manufacturer [figure1a,b,c]. A secondary sensitivity analysis considered confounding factors affecting WMH burden, including cardiovascular disease, smoking, HTN, dyslipidemia, diabetes, obstructive sleep apnea (OSA), chronic kidney disease, and orthostatic lightheadedness.

Results: PSP patients had a higher WMH burden than PD patients (0.55% vs. 0.29% of total ICV, Wilcoxon p=0.001). Multivariable linear regression confirmed the diagnosis effect (PSP > PD, beta=0.28, p=0.00041), even after adjusting for age. The effect remained significant after accounting for 8 cardiometabolic variables (PSP > PD, beta=0.24, p=0.0025). Significant associations with WMH included smoking (beta=0.63, p=0.002) and OSA (beta=0.52, p=0.005).

Conclusion: Our findings demonstrate increased WMH in PSP compared to PD, even after adjusting for vascular risk factors, suggesting that WMH differences may reflect distinct neurobiological mechanisms. The WMH quantification using this novel AI tool supports its potential as a biomarker to differentiate PSP from PD.

Figure 1

References: Jecmenica Lukic M, Kurz C, Respondek G, et al. Copathology in Progressive Supranuclear Palsy: Does It Matter? Movement disorders : official journal of the Movement Disorder Society. 2020;35(6):984-993. doi:https://doi.org/10.1002/mds.28011

Colosimo C, Osaki Y, Vanacore N, Lees AJ. Lack of association between progressive supranuclear palsy and arterial hypertension: A clinicopathological study. Movement Disorders. 2003;18(6):694-697. doi:https://doi.org/10.1002/mds.10392

Rabadia SV, Litvan I, Juncos J, et al. Hypertension and progressive supranuclear palsy. Parkinsonism & Related Disorders. 2019;66:166-170. doi:https://doi.org/10.1016/j.parkreldis.2019.07.036

‌Ghika J, Julien Bogousslavsky. Presymptomatic Hypertension Is a Major Feature in the Diagnosis of Progressive Supranuclear Palsy. Archives of neurology. 1997;54(9):1104-1108. doi:https://doi.org/10.1001/archneur.1997.00550210038010

‌Raz L, Bhaskar K, Weaver J, et al. Hypoxia promotes tau hyperphosphorylation with associated neuropathology in vascular dysfunction. Neurobiology of Disease. 2019;126:124-136. doi:https://doi.org/10.1016/j.nbd.2018.07.009

‌Kapasi A, Yu L, V. Petyuk, K. Arfanakis, Bennett DA, Schneider JA. Association of small vessel disease with tau pathology. Acta Neuropathologica. 2022;143(3):349-362. doi:https://doi.org/10.1007/s00401-021-02397-x

‌Merlini M, Wanner D, Nitsch RM. Tau pathology-dependent remodelling of cerebral arteries precedes Alzheimer’s disease-related microvascular cerebral amyloid angiopathy. Acta Neuropathologica. 2016;131(5):737-752. doi:https://doi.org/10.1007/s00401-016-1560-2

‌Gibson E, Ramirez J, Woods LA, et al. segcsvdWMH: A convolutional neural network-based tool for quantifying white matter hyperintensities in heterogeneous patient cohorts. medRxiv (Cold Spring Harbor Laboratory). Published online June 21, 2024. doi:https://doi.org/10.1101/2024.06.20.24309230

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MDS Abstracts - https://www.mdsabstracts.org/abstract/white-matter-abnormalities-in-progressive-supranuclear-palsy-psp-vs-parkinsons-disease-pd-evaluation-with-a-convolutional-neural-network-cnn-based-tool/