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
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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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Retinal Dysfunction in Alzheimer's Disease and Implications for Biomarkers.
TL;DR: In this article, the evidence of retinal dysfunction in Alzheimer's disease, particularly at the early stage, together with the underlying molecular mechanisms are reviewed and compared with other ophthalmological diseases and summarized potential retinal biomarkers measurable by existing technologies for detecting AD.
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Transgene distribution and immune response after ultrasound delivery of rAAV9 and PHP.B to the brain in a mouse model of amyloidosis.
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TL;DR: In this article, the authors investigated the transduction efficiency and immunological response following non-invasive gene-delivery strategies to the brain of a mouse model of amyloidosis.
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Adapting to dementia in society: a challenge for our lifetimes and a charge for public health.
TL;DR: An approach to brain health that eschews singular, short- and medium-term methodology and instead reflects long-term complexity is recommended, consistent with the ecological models of public health, which emphasize the development of community infrastructure that can foster population and individual health over the life-course by minimizing risk through multifaceted, systemic approaches.
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A double-dichotomy clustering of dual pathology dementia patients.
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TL;DR: The double-dichotomy clustering based on imaging and fluid biomarkers offers an unbiased method for identifying mixed dementia patients and selecting better defined sub-groups and supports the hypothesis that the categories of dementia represent different etiologies.
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Influence of APOE and RNF219 on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer's Disease.
Alessandra Mosca,Samantha Sperduti,Viorela Pop,Domenico Ciavardelli,Alberto Granzotto,Miriam Punzi,Liborio Stuppia,Valentina Gatta,Francesca Assogna,Nerisa Banaj,Fabrizio Piras,Federica Piras,Carlo Caltagirone,Gianfranco Spalletta,Stefano L. Sensi +14 more
TL;DR: Analysis of interactions between APOE-𝜀4 and RNF219/G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI) or AD revealed a novel synergistic activity APOE and R NF219 in the modification of behavioral traits of female MCI and AD patients.
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