Hase, Y, Polvikoski, TM, Firbank, MJ et al. (13 more authors) (2020) Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction. Brain Pathology, 30 (1). pp. 191-202. ISSN 1015-6305
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 International Society of Neuropathology. This is the peer reviewed version of the following article: Hase, Y., Polvikoski, T.M., Firbank, M.J., Craggs, L.J.L., Hawthorne, E., Platten, C., Stevenson, W., Deramecourt, V., Ballard, C., Kenny, R.A., Perry, R.H., Ince, P., Carare, R.O., Allan, L.M., Horsburgh, K. and Kalaria, R.N. (2020), Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction. Brain Pathol, 30: 191-202. doi:10.1111/bpa.12769, which has been published in final form at https://doi.org/10.1111/bpa.12769. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Alzheimer's disease; autonomic dysfunction; dementia; dementia with Lewy bodies; microvascular pathology; Mixed dementia; Parkinson's disease with dementia; small vessel disease; vascular dementia |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 11 Sep 2019 14:54 |
Last Modified: | 29 Jul 2020 00:39 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/bpa.12769 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:150702 |