Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre
Jon B. Toledo,Steven E. Arnold,Kevin M. Raible,Johannes Brettschneider,Sharon X. Xie,Murray Grossman,Sarah E. Monsell,Walter A. Kukull,John Q. Trojanowski +8 more
TLDR
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.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.read more
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Diagnostic Assessment & Prognosis Revolutionizing Alzheimer's disease and clinical trials through biomarkers
Niklas Mattsson,Maria C. Carrillo,Robert A. Dean,Michael D. Devous,Tania Nikolcheva,Pedro Pesini,William Z. Potter,Reisa S. Sperling,Randall J. Bateman,Lisa J. Bain,Enchi Liu +10 more
TL;DR: The Alzheimer's Association's Research Roundtable met in May 2014 to explore recent progress in developing biomarkers to improve understanding of disease pathogenesis and expedite drug development as mentioned in this paper, which is a clear need to develop novel biomarkers that are minimally invasive and that more broadly characterize underlying pathogenic mechanisms, including neurodegeneration, neuroinflammation, and synaptic dysfunction.
Journal ArticleDOI
Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy Magnetic Resonance Imaging Measurements in Alzheimer's Disease.
Michel Bilello,Jimit Doshi,S. Ali Nabavizadeh,Jon B. Toledo,Guray Erus,Sharon X. Xie,John Q. Trojanowski,Xiaoyan Han,Christos Davatzikos +8 more
TL;DR: Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy, highlighting the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly.
Journal ArticleDOI
Blood will out: vascular contributions to Alzheimer’s disease
TL;DR: The complexity of AD is discussed and possible cause-and-effect relationships between A&bgr; and the vascular and hemostatic systems are discussed and specific pathologies, including vascular pathways, can be therapeutically targeted.
Journal ArticleDOI
Post-Stroke Cognitive Impairment and Dementia.
Natalia S. Rost,Amy Brodtmann,Matthew P. Pase,Susanne J. van Veluw,Alessandro Biffi,Marco Duering,Jason D Hinman,Martin Dichgans +7 more
TL;DR: Recent developments in the field are summarized, future directions are discussed, and a call for action to systematically include cognitive outcome assessment into any clinical studies of poststroke outcome is called for.
Journal ArticleDOI
Cilostazol Add-On Therapy in Patients with Mild Dementia Receiving Donepezil: A Retrospective Study
Masafumi Ihara,Madoka Nishino,Akihiko Taguchi,Yumi Yamamoto,Yorito Hattori,Satoshi Saito,Yukako Takahashi,Masahiro Tsuji,Yukiko Kasahara,Yu Takata,Masahiro Okada +10 more
TL;DR: Potential for cilostazol treatment in the suppression of cognitive decline in patients receiving donepezil with mild dementia but not in those with moderate/severe dementia is suggested.
References
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Brain Infarction and the Clinical Expression of Alzheimer Disease: The Nun Study
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TL;DR: Findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
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