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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Plasma total prion protein as a potential biomarker for neurodegenerative dementia: diagnostic accuracy in the spectrum of prion diseases.
Franc Llorens,Franc Llorens,Anna Villar-Piqué,Matthias Schmitz,Daniela Diaz-Lucena,M. Wohlhage,Peter Hermann,Stefan Goebel,I. Schmidt,Markus Glatzel,Jean-Jacques Hauw,Beata Sikorska,Pawel P. Liberski,Joachim Riggert,Isidro Ferrer,Isidro Ferrer,Isidro Ferrer,Inga Zerr +17 more
TL;DR: The concentration of total prion protein (t‐PrP) in the plasma of neurodegenerative dementias is characterized and its accuracy in this differential diagnostic context is assessed.
Journal ArticleDOI
"Alzheimer's disease" is neither "Alzheimer's clinical syndrome" nor "dementia".
William J. Jagust,Clifford R. Jack,David A. Bennett,Kaj Blennow,Samantha Budd Haeberlein,David M. Holtzman,Frank Jessen,Jason Karlawish,Enchi Liu,José Luis Molinuevo,Thomas J. Montine,Creighton H. Phelps,Katherine P. Rankin,Christopher C. Rowe,Philip Scheltens,Eric Siemers,Reisa A. Sperling +16 more
TL;DR: The authors misunderstand a central issue addressed in the framework: the fundamental definition of Alzheimer's disease (AD) and its distinction from the terms “Alzheimer’s clinical syndrome” and dementia, and propose these terms to distinguish between the pathological features of the disease and its clinical consequences.
Journal ArticleDOI
Modeling the Relationships Among Late-Life Body Mass Index, Cerebrovascular Disease, and Alzheimer’s Disease Neuropathology in an Autopsy Sample of 1,421 Subjects from the National Alzheimer’s Coordinating Center Data Set
Michael L. Alosco,Jonathan Duskin,Lilah M. Besser,Brett Martin,Christine E. Chaisson,John Gunstad,Neil W. Kowall,Ann C. McKee,Robert S. Stern,Yorghos Tripodis +9 more
TL;DR: Lower late-life BMI may be a preclinical indicator of underlying ADNP, and joint modeling examined relationships among BMI, IIS, and ADNP in the overall sample and stratified by initial visit Clinical Dementia Rating score confirmed lower late- life BMI confers increased odds for ADNP.
Journal ArticleDOI
Amyloid and cerebrovascular burden divergently influence brain functional network changes over time.
Joanna Su Xian Chong,Hyemin Jang,Hee Jin Kim,Kwun Kei Ng,Duk L. Na,Jae-Hong Lee,Sang Won Seo,Juan Zhou +7 more
TL;DR: The findings underscore the divergent effects of Aβ and cerebrovascular burden on longitudinal FC changes in the DMN and ECN in the predementia stage, which reflect the underlying pathology and may be used to track early changes in Alzheimer disease and cereBrovascular disease.
Journal ArticleDOI
AMPK: Potential Therapeutic Target for Alzheimer's Disease.
TL;DR: Results demonstrated that activation of AMPK is controversial in Aβ deposition and tau phosphorylation, but is positive to promote autophagy, maintain mitochondrial quality control, reduce insulin resistance and oxidative stress, and it is concluded that AMPK might be a new target for AD by aggressively treating the risk factors in the future.
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