title: Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre.
abstract: Cerebrovascular disease and vascular risk factors are associated with Alzheimer's disease, but the evidence for their association with other neurodegenerative disorders is limited. Therefore, we compared the prevalence of cerebrovascular disease, vascular pathology and vascular risk factors in a wide range of neurodegenerative diseases and correlate them with dementia severity. Presence of cerebrovascular disease, vascular pathology and vascular risk factors was studied in 5715 cases of the National Alzheimer's Coordinating Centre database with a single neurodegenerative disease diagnosis (Alzheimer's disease, frontotemporal lobar degeneration due to tau, and TAR DNA-binding protein 43 immunoreactive deposits, α-synucleinopathies, hippocampal sclerosis and prion disease) based on a neuropathological examination with or without cerebrovascular disease, defined neuropathologically. In addition, 210 'unremarkable brain' cases without cognitive impairment, and 280 cases with pure cerebrovascular disease were included for comparison. Cases with cerebrovascular disease were older than those without cerebrovascular disease in all the groups except for those with hippocampal sclerosis. After controlling for age and gender as fixed effects and centre as a random effect, we observed that α-synucleinopathies, frontotemporal lobar degeneration due to tau and TAR DNA-binding protein 43, and prion disease showed a lower prevalence of coincident cerebrovascular disease than patients with Alzheimer's disease, and this was more significant in younger subjects. When cerebrovascular disease was also present, patients with Alzheimer's disease and patients with α-synucleinopathy showed relatively lower burdens of their respective lesions than those without cerebrovascular disease in the context of comparable severity of dementia at time of death. Concurrent cerebrovascular disease is a common neuropathological finding in aged subjects with dementia, is more common in Alzheimer's disease than in other neurodegenerative disorders, especially in younger subjects, and lowers the threshold for dementia due to Alzheimer's disease and α-synucleinopathies, which suggests that these disorders should be targeted by treatments for cerebrovascular disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute on Ageing, Centre for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.forename: Kevin
authors.initials: K
authors.lastname: Raible
authors.forename: Johannes
authors.initials: J
authors.lastname: Brettschneider
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Xie
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Monsell
authors.forename: Walter A
authors.initials: WA
authors.lastname: Kukull
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy / Q000379:methods*; D002561:Cerebrovascular Disorders / Q000150:complications* / Q000453:epidemiology*; D015140:Dementia, Vascular / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006306:Health Surveys / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D054561:National Institute on Aging (U.S.) / Q000706:statistics & numerical data; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D015995:Prevalence; D012307:Risk Factors; D012737:Sex Factors; D014481:United States
keywords: Alzheimer’s disease; dementia; epidemiology; frontotemporal lobar degeneration; neuropathology; vascular disease