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Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction.
Brain Pathol. 2020 01; 30(1):191-202.BP

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.

Authors+Show Affiliations

Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.Histology and Pathology Department, Lille University Hospital, University Lille Nord de France, Lille, France.School of Medicine, University of Exeter, Exeter, United Kingdom.Department of Medical Gerontology, Trinity College Dublin, Dublin, Ireland.Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, United Kingdom.Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.School of Medicine, University of Exeter, Exeter, United Kingdom.Centre for Neuroregeneration, University of Edinburgh, Little France Crescent, Edinburgh, United Kingdom.Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31357238

Citation

Hase, Yoshiki, et al. "Small Vessel Disease Pathological Changes in Neurodegenerative and Vascular Dementias Concomitant With Autonomic Dysfunction." Brain Pathology (Zurich, Switzerland), vol. 30, no. 1, 2020, pp. 191-202.
Hase Y, Polvikoski TM, Firbank MJ, et al. Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction. Brain Pathol. 2020;30(1):191-202.
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., & Kalaria, R. N. (2020). Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction. Brain Pathology (Zurich, Switzerland), 30(1), 191-202. https://doi.org/10.1111/bpa.12769
Hase Y, et al. Small Vessel Disease Pathological Changes in Neurodegenerative and Vascular Dementias Concomitant With Autonomic Dysfunction. Brain Pathol. 2020;30(1):191-202. PubMed PMID: 31357238.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction. AU - Hase,Yoshiki, AU - Polvikoski,Tuomo M, AU - Firbank,Michael J, AU - Craggs,Lucinda J L, AU - Hawthorne,Emily, AU - Platten,Charlotte, AU - Stevenson,William, AU - Deramecourt,Vincent, AU - Ballard,Clive, AU - Kenny,Rose Anne, AU - Perry,Robert H, AU - Ince,Paul, AU - Carare,Roxana O, AU - Allan,Louise M, AU - Horsburgh,Karen, AU - Kalaria,Raj N, Y1 - 2019/08/16/ PY - 2019/02/27/received PY - 2019/07/21/accepted PY - 2019/7/30/pubmed PY - 2020/9/30/medline PY - 2019/7/30/entrez KW - Alzheimer's disease KW - Mixed dementia KW - Parkinson's disease with dementia KW - autonomic dysfunction KW - dementia KW - dementia with Lewy bodies KW - microvascular pathology KW - small vessel disease KW - vascular dementia SP - 191 EP - 202 JF - Brain pathology (Zurich, Switzerland) JO - Brain Pathol VL - 30 IS - 1 N2 - 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. SN - 1750-3639 UR - https://www.unboundmedicine.com/medline/citation/31357238/Small_vessel_disease_pathological_changes_in_neurodegenerative_and_vascular_dementias_concomitant_with_autonomic_dysfunction_ L2 - https://doi.org/10.1111/bpa.12769 DB - PRIME DP - Unbound Medicine ER -