TY - JOUR
T1 - The correlation between neuropathology levels and cognitive performance in centenarians
AU - Zhang, Meng
AU - Ganz, Andrea B.
AU - Rohde, Susan
AU - Lorenz, Linda
AU - Rozemuller, Annemieke J. M.
AU - van Vliet, Kimberley
AU - Graat, Marieke
AU - Sikkes, Sietske A. M.
AU - Reinders, Marcel J. T.
AU - Scheltens, Philip
AU - Hulsman, Marc
AU - Hoozemans, Jeroen J. M.
AU - Holstege, Henne
N1 - Funding Information:
The authors thank and acknowledge all participating centenarians and their family members and the team who visited the centenarians over the years: Chandeny, Debbie, Elizabeth, Esther, Ilse, Karlijn, Kimberley, Kimja, Linda, Linette, Marieke, Nina, Sanne, Sterre, and Tjitske for collecting the neuropsychological data. Finally, this work would not have been possible without the great collaboration we have enjoyed with the wonderful staff of the Netherlands Brain Bank. This work was supported by BrightFocus A2021031S and Stichting VUmc Fonds. H.H. and M.J.T.R. are recipients of ABOARD, a public‐private partnership receiving funding from ZonMW (73305095007) and Health∼Holland, Topsector Life Sciences & Health (PPP‐allowance; LSHM20106). H.H. was supported by the Hans und Ilse Breuer Stiftung (2020) and the HorstingStuit Foundation (2018).
Publisher Copyright:
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2023
Y1 - 2023
N2 - INTRODUCTION: Neuropathological substrates associated with neurodegeneration occur in brains of the oldest old. How does this affect cognitive performance?. METHODS: The 100-plus Study is an ongoing longitudinal cohort study of centenarians who self-report to be cognitively healthy; post mortem brain donation is optional. In 85 centenarian brains, we explored the correlations between the levels of 11 neuropathological substrates with ante mortem performance on 12 neuropsychological tests. RESULTS: Levels of neuropathological substrates varied: we observed levels up to Thal-amyloid beta phase 5, Braak-neurofibrillary tangle (NFT) stage V, Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-neuritic plaque score 3, Thal-cerebral amyloid angiopathy stage 3, Tar-DNA binding protein 43 (TDP-43) stage 3, hippocampal sclerosis stage 1, Braak-Lewy bodies stage 6, atherosclerosis stage 3, cerebral infarcts stage 1, and cerebral atrophy stage 2. Granulovacuolar degeneration occurred in all centenarians. Some high performers had the highest neuropathology scores. DISCUSSION: Only Braak-NFT stage and limbic-predominant age-related TDP-43 encephalopathy (LATE) pathology associated significantly with performance across multiple cognitive domains. Of all cognitive tests, the clock-drawing test was particularly sensitive to levels of multiple neuropathologies.
AB - INTRODUCTION: Neuropathological substrates associated with neurodegeneration occur in brains of the oldest old. How does this affect cognitive performance?. METHODS: The 100-plus Study is an ongoing longitudinal cohort study of centenarians who self-report to be cognitively healthy; post mortem brain donation is optional. In 85 centenarian brains, we explored the correlations between the levels of 11 neuropathological substrates with ante mortem performance on 12 neuropsychological tests. RESULTS: Levels of neuropathological substrates varied: we observed levels up to Thal-amyloid beta phase 5, Braak-neurofibrillary tangle (NFT) stage V, Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-neuritic plaque score 3, Thal-cerebral amyloid angiopathy stage 3, Tar-DNA binding protein 43 (TDP-43) stage 3, hippocampal sclerosis stage 1, Braak-Lewy bodies stage 6, atherosclerosis stage 3, cerebral infarcts stage 1, and cerebral atrophy stage 2. Granulovacuolar degeneration occurred in all centenarians. Some high performers had the highest neuropathology scores. DISCUSSION: Only Braak-NFT stage and limbic-predominant age-related TDP-43 encephalopathy (LATE) pathology associated significantly with performance across multiple cognitive domains. Of all cognitive tests, the clock-drawing test was particularly sensitive to levels of multiple neuropathologies.
UR - http://www.scopus.com/inward/record.url?scp=85153490471&partnerID=8YFLogxK
U2 - 10.1002/alz.13087
DO - 10.1002/alz.13087
M3 - Article
C2 - 37092333
SN - 1552-5260
JO - Alzheimers & Dementia
JF - Alzheimers & Dementia
ER -