Association of TDP-43 proteinopathy, cerebral amyloid angiopathy, and Lewy bodies with cognitive impairment in individuals with or without Alzheimer's disease neuropathology.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 09 2020
03 09 2020
Historique:
received:
11
02
2020
accepted:
14
07
2020
entrez:
5
9
2020
pubmed:
5
9
2020
medline:
26
3
2021
Statut:
epublish
Résumé
Alzheimer's disease patients typically present with multiple co-morbid neuropathologies at autopsy, but the impact of these pathologies on cognitive impairment during life is poorly understood. In this study, we developed cognitive trajectories for patients with common co-pathologies in the presence and absence of Alzheimer's disease neuropathology. Cognitive trajectories were modelled in a Bayesian hierarchical regression framework to estimate the effects of each neuropathology on cognitive decline as assessed by the mini-mental state examination and the clinical dementia rating scale sum of boxes scores. We show that both TDP-43 proteinopathy and cerebral amyloid angiopathy associate with cognitive impairment of similar magnitude to that associated with Alzheimer's disease neuropathology. Within our study population, 63% of individuals given the 'gold-standard' neuropathological diagnosis of Alzheimer's disease in fact possessed either TDP-43 proteinopathy or cerebral amyloid angiopathy of sufficient severity to independently explain the majority of their cognitive impairment. This suggests that many individuals diagnosed with Alzheimer's disease may actually suffer from a mixed dementia, and therapeutics targeting only Alzheimer's disease-related processes may have severely limited efficacy in these co-morbid populations.
Identifiants
pubmed: 32883971
doi: 10.1038/s41598-020-71305-2
pii: 10.1038/s41598-020-71305-2
pmc: PMC7471113
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14579Subventions
Organisme : NIA NIH HHS
ID : P50 AG005142
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010133
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005146
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG008017
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG025688
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005133
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005138
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047366
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG028383
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013854
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG053760
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062428
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010124
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG023501
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062421
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG035982
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG008702
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG008051
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005681
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013846
Pays : United States
Organisme : Medical Research Council
ID : MC_UP_1604/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P50 AG047270
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062429
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005136
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG049638
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG012300
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062422
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016573
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047266
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00024/8
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : Medical Research Council
ID : MR/R015600/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG062715
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066468
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010129
Pays : United States
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