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Clinical and neuropathological diagnoses in 112 demented subjects comprised dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Alzheimer's disease (AD), Mixed dementia (mostly AD\u2010DLB) and vascular dementia (VaD). Of these, 12 DLB subjects had no recorded unexpected falls in life and therefore no evidence of concomitant autonomic dysfunction. A further 17 subjects were assessed as aging controls without significant pathology or signs of autonomic dysfunction. We quantified brain vascular pathological changes and determined severities of neurodegenerative lesions including \u03b1\u2010synuclein pathology. We found moderate\u2010severe vascular changes and high\u2010vascular pathology scores (<jats:italic>P\u00a0&lt;\u00a0<\/jats:italic>0.01) in all neurodegenerative dementias and as expected in VaD compared to similar age controls. Arteriolosclerosis, perivascular spacing and microinfarcts were frequent in the basal ganglia and frontal white matter (WM) across all dementias, whereas small infarcts (&lt;5\u00a0mm) were restricted to VaD. In a sub\u2010set of demented subjects, we found that vascular pathology scores were correlated with WM hyperintensity volumes determined by MRI in life (<jats:italic>P\u00a0&lt;\u00a0<\/jats:italic>0.02). Sclerotic index values were increased by ~50% in both the WM and neocortex in all dementias compared to similar age controls. We found no evidence for increased \u03b1\u2010synuclein deposition in subjects with autonomic dysfunction. Our findings suggest greater SVD pathological changes occur in the elderly diagnosed with neurodegenerative dementias including DLB and who develop autonomic dysfunction. SVD changes may not necessarily manifest in clinically overt symptoms but they likely confound motor or cognitive dysfunction. We propose dysautonomia promotes chronic cerebral hypoperfusion to impact upon aging\u2010related neurodegenerative disorders and characterize their end\u2010stage clinical syndromes.<\/jats:p>","DOI":"10.1111\/bpa.12769","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T22:38:04Z","timestamp":1564439884000},"page":"191-202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction"],"prefix":"10.1111","volume":"30","author":[{"given":"Yoshiki","family":"Hase","sequence":"first","affiliation":[{"name":"Institute of Neuroscience Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomo M.","family":"Polvikoski","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Firbank","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Newcastle University Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucinda J. 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