{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:43:21Z","timestamp":1784004201151,"version":"3.55.0"},"reference-count":111,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["17253"],"award-info":[{"award-number":["17253"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Motor and cognitive impairment in Parkinson's disease (PD) is associated with dopaminergic dysfunction that stems from substantia nigra (SN) degeneration and concomitant \u03b1\u2010synuclein accumulation. Diffusion magnetic resonance imaging (MRI) can detect microstructural alterations of the SN and its tracts to (sub)cortical regions, but their pathological sensitivity is still poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To unravel the pathological substrate(s) underlying microstructural alterations of SN, and its tracts to the dorsal striatum and dorsolateral prefrontal cortex (DLPFC) in PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Combining post\u2010mortem in situ MRI and histopathology, T1\u2010weighted and diffusion MRI, and neuropathological samples of nine PD, six PD with dementia (PDD), five dementia with Lewy bodies (DLB), and 10 control donors were collected. From diffusion MRI, mean diffusivity (MD) and fractional anisotropy (FA) were derived from the SN, and tracts between the SN and caudate nucleus, putamen, and DLPFC. Phosphorylated\u2010Ser129\u2010\u03b1\u2010synuclein and tyrosine hydroxylase immunohistochemistry was included to quantify nigral Lewy pathology and dopaminergic degeneration, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to controls, PD and PDD\/DLB showed increased MD of the SN and SN\u2010DLPFC tract, as well as increased FA of the SN\u2010caudate nucleus tract. Both PD and PDD\/DLB showed nigral Lewy pathology and dopaminergic loss compared to controls. Increased MD of the SN and FA of SN\u2010caudate nucleus tract were associated with SN dopaminergic loss. Whereas increased MD of the SN\u2010DLPFC tract was associated with increased SN Lewy neurite load.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In PD and PDD\/DLB, diffusion MRI captures microstructural alterations of the SN and tracts to the dorsal striatum and DLPFC, which differentially associates with SN dopaminergic degeneration and Lewy neurite pathology. \u00a9 2023 The Authors.\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  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