Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Peak width of skeletonized mean diffusivity reveals early and multifactorial white matter injury across sporadic and Down syndrome-associated Alzheimer's disease.
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Morcillo-Nieto Alejandra O, Franquesa-Mullerat Maria, Zsadanyi Sara E, Arriola-Infante José Enrique, Vaqué-Alcázar Lídia, Rozalem-Aranha Mateus, Parra José Allende, Zhao Zili, Arranz Javier, Rodríguez-Baz Íñigo, Maure-Blesa Lucia, Videla Laura, Barroeta Isabel, Del Hoyo Soriano Laura, Benejam Bessy, Fernández Susana, Sanjuan Hernandez Aida, Pertierra Lucia, Giménez Sandra, Santos-Santos Miguel, Dols-Icardo Oriol, Illán-Gala Ignacio, Alcolea Daniel, Belbin Olivia, Lleó Alberto, Carmona-Iragui María, Fortea Juan, Bejanin Alexandre
Аннотация
INTRODUCTION: This study investigates the evolution with disease progression and pathological correlates of peak width of skeletonized mean diffusivity (PSMD), a sensitive diffusion magnetic resonance imaging (MRI) marker of microvascular white matter (WM) injury, in sporadic Alzheimer's disease (sAD) and Down syndrome (DS)-associated AD (DSAD).
METHOD: This cross-sectional study included 150 euploid controls, 118 subjects with sAD, and 228 DS adults (34.65% with symptomatic AD). PSMD was derived from 3T-MRI diffusion tensor imaging. Associations with sociodemographic, clinical stage, cerebrospinal fluid (CSF), and small vessel disease markers were examined.
RESULTS: PSMD correlated with age in all groups, showing a stronger association in DS, with alterations apparent 15 years before the population's dementia age at onset. In euploid and DS, higher PSMD correlated with AD severity, CSF-neurofilament light chain (NfL), microbleeds, and WM hyperintensities (WMH). PSMD abnormalities were more frequent than WMH, especially in DS.
DISCUSSION: PSMD is a sensitive early biomarker of WM injury across sAD and DSAD, preceding symptom onset and capturing multifactorial disease processes.
METHOD: This cross-sectional study included 150 euploid controls, 118 subjects with sAD, and 228 DS adults (34.65% with symptomatic AD). PSMD was derived from 3T-MRI diffusion tensor imaging. Associations with sociodemographic, clinical stage, cerebrospinal fluid (CSF), and small vessel disease markers were examined.
RESULTS: PSMD correlated with age in all groups, showing a stronger association in DS, with alterations apparent 15 years before the population's dementia age at onset. In euploid and DS, higher PSMD correlated with AD severity, CSF-neurofilament light chain (NfL), microbleeds, and WM hyperintensities (WMH). PSMD abnormalities were more frequent than WMH, especially in DS.
DISCUSSION: PSMD is a sensitive early biomarker of WM injury across sAD and DSAD, preceding symptom onset and capturing multifactorial disease processes.