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
Citations
More filters
Journal ArticleDOI
Solving neurodegeneration: common mechanisms and strategies for new treatments
Lauren K. Wareham,Shane A. Liddelow,Sally Temple,Larry I. Benowitz,Adriana Di Polo,Cheryl L. Wellington,Jeffrey L. Goldberg,Zhigang He,Xin Duan,Guojun Bu,Albert A. Davis,Karthik Shekhar,Anna La Torre,David C. Chan,M. Valeria Canto-Soler,John G. Flanagan,Preeti Subramanian,Sharyn L. Rossi,Thomas Brunner,Diane E. Bovenkamp,David J. Calkins +20 more
TL;DR: Solving Neurodegeneration as discussed by the authors is a virtual meeting focused on uncovering common mechanistic roots of neurodegenerative disease and promising targets for new treatments, catalyzed by the goal of finding new treatments for glaucoma, the leading cause of irreversible blindness and the common interest of the three hosting foundations.
Journal ArticleDOI
Growth differentiation factor-15 and white matter hyperintensities in cognitive impairment and dementia.
Yuek Ling Chai,Saima Hilal,Jenny P.C. Chong,Y.X. Ng,O.W. Liew,Xin Xu,Mohammad Kamran Ikram,N. Venketasubramanian,Arthur Mark Richards,Mitchell K.P. Lai,Christopher Chen +10 more
TL;DR: It is shown that increased GDF-15 may be a biomarker for CIND and AD in subjects with WMH, and the associations between G DF-15 and cognitive impairment as well as withWMH remained significant after excluding subjects with cardiovascular diseases.
Journal ArticleDOI
Alzheimer's/Vascular Spectrum Dementia: Classification in Addition to Diagnosis.
Sheina Emrani,Melissa Lamar,Catherine C. Price,Victor Wasserman,Emily F Matusz,Rhoda Au,Rodney Swenson,Robert G. Nagele,Kenneth M. Heilman,David J. Libon +9 more
TL;DR: It is proposed that in conjunction with current diagnostic criteria, statistical modeling techniques using neuropsychological test performance should be leveraged to construct a system to classify AD/VaD spectrum dementia in order to test hypotheses regarding how mechanisms related to AD and VaD pathology interact and influence each other.
Journal ArticleDOI
Contributions of Aging to Cerebral Small Vessel Disease.
TL;DR: This review summarizes recent progress and concepts in cerebral small vessel disease, highlighting key findings and some major unanswered questions and focuses on phenotypes and mechanisms that underlie microvascular aging, the greatest risk factor for cerebrovascular disease and its subsequent effects.
Journal ArticleDOI
Therapeutic Strategies and Drug Development for Vascular Cognitive Impairment
Eric E. Smith,Alicja Cieslak,Philip A. Barber,Jerry Chen,Yu-Wei Chen,Ida Donnini,Jodi D. Edwards,Richard Frayne,Thalia S. Field,Janka Hegedus,Victoria Hanganu,Zahinoor Ismail,Jamila Kanji,Makoto Nakajima,Raza Noor,Stefano Peca,Demetrios J. Sahlas,Mukul Sharma,Luciano A. Sposato,Richard H. Swartz,Charlotte Zerna,Sandra E. Black,Vladimir Hachinski +22 more
TL;DR: Trial design and drug development for vascular cognitive impairment (VCI) is reviewed, focusing on symptomatic patients with vascular mild cognitive impairment or dementia, and axes along which vascular components of cognitive impairment can be addressed are reviewed.
References
More filters
Book
Mixed-Effects Models in S and S-PLUS
TL;DR: Linear Mixed-Effects and Nonlinear Mixed-effects (NLME) models have been studied in the literature as mentioned in this paper, where the structure of grouped data has been used for fitting LME models.
MonographDOI
Categorical data analysis
TL;DR: In this article, the authors present a generalized linear model for categorical data, which is based on the Logit model, and use it to fit Logistic Regression models.
Journal ArticleDOI
Vascular Contributions to Cognitive Impairment and Dementia A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association
Philip B. Gorelick,Angelo Scuteri,Sandra E. Black,Charles DeCarli,Steven M. Greenberg,Costantino Iadecola,Lenore J. Launer,Stéphane Laurent,Oscar L. Lopez,David L. Nyenhuis,Ronald C. Petersen,Julie A. Schneider,Christophe Tzourio,Donna K. Arnett,David A. Bennett,Helena C. Chui,Randall T. Higashida,Ruth Lindquist,Peter M. Nilsson,Gustavo C. Román,Frank W. Sellke,Sudha Seshadri +21 more
TL;DR: This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia and provides evidence that subcortical forms of VCI with white matter hyperintensities and small deep infarcts are common and risk markers for VCI are the same as traditional risk factors for stroke.
Journal ArticleDOI
Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry.
TL;DR: To better meet the demands of routine laboratories this procedure is revised here by adapting tissue selection and processing to the needs of paraffin-embedded sections and by introducing a robust immunoreaction (AT8) for hyperphosphorylated tau protein that can be processed on an automated basis.
Journal ArticleDOI
Brain Infarction and the Clinical Expression of Alzheimer Disease: The Nun Study
David A. Snowdon,Lydia H. Greiner,James A. Mortimer,Kathryn P. Riley,Philip A. Greiner,William R. Markesbery +5 more
TL;DR: Findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
Related Papers (5)
Vascular Contributions to Cognitive Impairment and Dementia A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association
Philip B. Gorelick,Angelo Scuteri,Sandra E. Black,Charles DeCarli,Steven M. Greenberg,Costantino Iadecola,Lenore J. Launer,Stéphane Laurent,Oscar L. Lopez,David L. Nyenhuis,Ronald C. Petersen,Julie A. Schneider,Christophe Tzourio,Donna K. Arnett,David A. Bennett,Helena C. Chui,Randall T. Higashida,Ruth Lindquist,Peter M. Nilsson,Gustavo C. Román,Frank W. Sellke,Sudha Seshadri +21 more
The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease
Guy M. McKhann,Guy M. McKhann,David S. Knopman,Howard Chertkow,Bradley T. Hyman,Clifford R. Jack,Claudia H. Kawas,William E. Klunk,Walter J. Koroshetz,Jennifer J. Manly,Richard Mayeux,Richard C. Mohs,John C. Morris,Martin N. Rossor,Philip Scheltens,Maria C. Carrillo,Bill Thies,Sandra Weintraub,Creighton H. Phelps +18 more
Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration
Joanna M. Wardlaw,Eric E. Smith,Geert J. Biessels,Charlotte Cordonnier,Franz Fazekas,Richard Frayne,Richard I. Lindley,John T. O'Brien,Frederik Barkhof,Oscar R. Benavente,Sandra E. Black,Carol Brayne,Monique M.B. Breteler,Hugues Chabriat,Charles DeCarli,Frank-Erik de Leeuw,Fergus N. Doubal,Marco Duering,Nick C. Fox,Steven M. Greenberg,Vladimir Hachinski,Ingo Kilimann,Vincent Mok,Robert J. van Oostenbrugge,Leonardo Pantoni,Oliver Speck,Blossom C. M. Stephan,Stefan J. Teipel,Anand Viswanathan,David J. Werring,Christopher Chen,Colin Smith,Mark A. van Buchem,Bo Norrving,Philip B. Gorelick,Martin Dichgans +35 more