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Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction.
Hase, Yoshiki; Polvikoski, Tuomo M; Firbank, Michael J; Craggs, Lucinda J L; Hawthorne, Emily; Platten, Charlotte; Stevenson, William; Deramecourt, Vincent; Ballard, Clive; Kenny, Rose Anne; Perry, Robert H; Ince, Paul; Carare, Roxana O; Allan, Louise M; Horsburgh, Karen; Kalaria, Raj N.
Afiliação
  • Hase Y; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Polvikoski TM; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Firbank MJ; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Craggs LJL; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Hawthorne E; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Platten C; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Stevenson W; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Deramecourt V; Histology and Pathology Department, Lille University Hospital, University Lille Nord de France, Lille, France.
  • Ballard C; School of Medicine, University of Exeter, Exeter, United Kingdom.
  • Kenny RA; Department of Medical Gerontology, Trinity College Dublin, Dublin, Ireland.
  • Perry RH; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Ince P; Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, United Kingdom.
  • Carare RO; Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
  • Allan LM; School of Medicine, University of Exeter, Exeter, United Kingdom.
  • Horsburgh K; Centre for Neuroregeneration, University of Edinburgh, Little France Crescent, Edinburgh, United Kingdom.
  • Kalaria RN; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.
Brain Pathol ; 30(1): 191-202, 2020 01.
Article em En | MEDLINE | ID: mdl-31357238
ABSTRACT
We performed a clinicopathological study to assess the burden of small vessel disease (SVD) type of pathological changes in elderly demented subjects, who had clinical evidence of autonomic dysfunction, either carotid sinus hypersensitivity or orthostatic hypotension or both or had exhibited unexpected repeated falls. 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-DLB) 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 α-synuclein pathology. We found moderate-severe vascular changes and high-vascular pathology scores (P < 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 (<5 mm) were restricted to VaD. In a sub-set of demented subjects, we found that vascular pathology scores were correlated with WM hyperintensity volumes determined by MRI in life (P < 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 α-synuclein 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-related neurodegenerative disorders and characterize their end-stage clinical syndromes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças do Sistema Nervoso Autônomo / Demência Vascular / Microvasos Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças do Sistema Nervoso Autônomo / Demência Vascular / Microvasos Idioma: En Ano de publicação: 2020 Tipo de documento: Article