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The diffusion tensor imaging\u2013analysis along the perivascular space (DTI\u2010ALPS) has been proposed as a non\u2010invasive MRI marker of glymphatic flow, although its biological specificity remains uncertain. This study aimed to identify the determinants of DTI\u2010ALPS and evaluate whether it primarily reflects white\u2010matter (WM) microstructure rather than glymphatic flow in the context of neurodegeneration. We examined 100 individuals referred to the Memory Clinic of the Policlinico Hospital in Milan for suspected dementia. All participants underwent a 3T\u2010MRI protocol including 3D\u2010T1\u2010weighted and 3D\u2010FLAIR imaging, double\u2010shell diffusion\u2010weighted imaging (\n                    <jats:italic>b<\/jats:italic>\n                    \u2009=\u20091000\/2000\u2009s\/mm\n                    <jats:sup>2<\/jats:sup>\n                    ), and multi\u2010echo gradient\u2010echo sequences for quantitative susceptibility mapping. Within standard DTI\u2010ALPS ROIs, we extracted DTI\u2010ALPS values together with fractional anisotropy (FA), mean diffusivity (MD), and mode of anisotropy (MA) at both\n                    <jats:italic>b<\/jats:italic>\n                    \u2010values, as well as neurite orientation and density imaging (NODDI) metrics, particularly the orientation dispersion index (ODI). WM microstructure was further characterized using the T1\/FLAIR ratio and diamagnetic component of susceptibility (DCS). DTI\u2010ALPS correlated inversely with MA (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009\u22120.84 at\n                    <jats:italic>b<\/jats:italic>\n                    \u2009=\u20091000;\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009\u22120.86 at\n                    <jats:italic>b<\/jats:italic>\n                    \u2009=\u20092000) and positively with ODI (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.73). Moderate correlations with the T1\/FLAIR ratio and DCS supported sensitivity to WM alterations. Factor analysis indicated that DTI\u2010ALPS clustered with MA and ODI rather than forming a distinct factor, suggesting that DTI\u2010ALPS primarily reflects WM diffusion dispersion and heterogeneity rather than glymphatic flow in the context of neurodegeneration.\n                  <\/jats:p>","DOI":"10.1002\/hbm.70603","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:37:23Z","timestamp":1790314643000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["DTI\u2010ALPS Primarily Reflects White Matter Diffusion Dispersion and Microstructural Heterogeneity in Neurodegeneration: Insights From Multi\u2010Modal MRI"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3929-9009","authenticated-orcid":false,"given":"Luca","family":"Sacchi","sequence":"first","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences University of 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