1. Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction
- Author
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Michael J. Firbank, Yoshiki Hase, Emily Hawthorne, Lucinda J. L. Craggs, Vincent Deramecourt, Tuomo Polvikoski, William Stevenson, Clive Ballard, Charlotte Platten, Raj N. Kalaria, Louise Allan, Roxana O. Carare, Paul G. Ince, Robert H. Perry, Rose Anne Kenny, and Karen Horsburgh
- Subjects
0301 basic medicine ,Lewy Body Disease ,medicine.medical_specialty ,Aging ,Arteriolosclerosis ,Neocortex ,Primary Dysautonomias ,Pathology and Forensic Medicine ,03 medical and health sciences ,Orthostatic vital signs ,0302 clinical medicine ,Alzheimer Disease ,Internal medicine ,mental disorders ,Medicine ,Dementia ,Vascular dementia ,Pathological ,Research Articles ,business.industry ,Dementia with Lewy bodies ,General Neuroscience ,Dementia, Vascular ,Dysautonomia ,Parkinson Disease ,medicine.disease ,Magnetic Resonance Imaging ,White Matter ,Hyperintensity ,030104 developmental biology ,Autonomic Nervous System Diseases ,Microvessels ,Cardiology ,alpha-Synuclein ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Autonomic dysfunction may affect brain blood flow and result in intermittent cerebral hypoperfusion, which is recognised as a cause of cognitive impairment and dementia. We assessed the burden of small vessel disease pathology in elderly subjects who had clinical evidence of autonomic dysfunction and had developed neurodegenerative dementias or vascular dementia (VaD). Clinical and neuropathological diagnosis in 118 subjects comprised dementia with Lewy bodies (DLB), Parkinson’s disease with dementia, Alzheimer’s disease (AD), Mixed dementia (mostly AD and DLB), VaD and ageing controls without significant pathology. Autonomic dysfunction was diagnosed in demented subjects who had clinical evidence of carotid sinus hypersensitivity or orthostatic hypotension or both. A subgroup of elderly demented subjects, who were reported to have unexplained falls in life were also analysed in parallel. Post-mortem brain tissues were stained using routine histopathological and immunocytochemical methods to quantify brain vascular and neurodegenerative lesions including hyperphosphorylated tau and α-synuclein. The frontal lobe grey and white matter (WM) in all cases was further assessed to quantify the degree of arteriolosclerosis using the sclerotic index (SI), microvascular density and capillary width using markers of the basement membrane (collagen IV; COL4) and the endothelium (glucose transporter-1; GLUT-1). We found moderate to severe vascular lesions and high vascular pathology scores (P
- Published
- 2020