Clinical validity of Braak neuropathological staging in the oldest-old

Gold, G.; Bouras, C.; Kövari, E.; Canuto, A.; González Glaría, B.; Malky, A.; Hof, P. R.; Michel, J.-P.; Giannakopoulos, P.

doi:10.1007/s004010051163

Cited by 129Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Clinical validity of Braak neuropathological staging in the oldest-old

Gold, G., Bouras, C., Kövari, E., Canuto, A., González Glaría, B., Malky, A., Hof, P. R., Michel, J.-P. +1 more·2000·Acta Neuropathologica

DOI 10.1007/s004010051163

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Abstract

Several studies have demonstrated a good correlation between clinical severity and Braak's neuropathological staging in Alzheimer's disease (AD). However, nonagenarians and centenarians display a different pattern of cortical vulnerability to the neurodegenerative process compared to younger elderly, and it is not known whether correlations between clinical severity and neuropathological stages remain valid in this age group. To address this issue we compared Clinical Dementia Rating scale (CDR) scores and Braak stages in 116 patients over 90 years of age with either no cognitive impairment or very mild to severe AD. There is a strong positive correlation between CDR scores and Braak staging (Spearman coefficient = 0.66; P < 0.01). However, neuropathological staging does not distinguish cases with normal cognition (CDR 0) from those with mild cognitive changes (CDR 0.5). Unlike younger cohorts, Braak stages I and II are frequently associated with questionable dementia in this age group. Braak stage III overlaps with all CDR levels and correlates poorly with cognitive function. Braak stages IV or greater are consistently associated with at least mild dementia. Consistent with our previous neuropathological analyses of nonagenarians and centenarians, the present data suggest that the substantial involvement of the hippocampus which characterizes Braak stage IV is a key step in the development of overt clinical signs of dementia in the oldest-old. Moreover, they indicate that Braak staging represents a broad concept of the evolution of neurofibrillary tangles rather than a precise hierarchical model associated with a stepwise deterioration of cognitive abilities near the upper limit of life.

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Numerous studies have documented a strong link between neocortical NFTs and cognitive loss.
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Authors: Gold, G., Bouras, C., Kövari, E., Canuto, A., González Glaría, B., Malky, A., Hof, P. R., Michel, J.-P., & Giannakopoulos, P.
Affiliations: University Hospital of Geneva (CH)
Icahn School of Medicine at Mount Sinai (US)
ORCID: Kövari, E.
Hof, P. R.
Giannakopoulos, P.
Venue: Acta Neuropathologica
Publisher: Springer Science and Business Media LLC
Published: 2000-05-30
Volume: 99
Issue: 5
Pages: 579-582
ISSN: 0001-6322 (ISSN-L)
1432-0533
DOI: 10.1007/s004010051163
OpenAlex: W2047542833
Cited by: 128
References: 20
Citations by year: 2026: 4 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 10 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 7 · 2013: 4 · 2012: 3
FWCI: 3.26
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Acta Neuropathologica (publishedVersion)
PubMed (publishedVersion)
Funders: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
National Institutes of Health
National Institute on Aging (AG 05138, P50AG005138)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Braak staging, Alzheimer's disease, oldest old, centenarians, nonagenarians, Clinical Dementia Rating, neurofibrillary tangles, hippocampal involvement, cognitive impairment, clinical validity
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition Disorders, Female, Humans, Male, Neurology, Reproducibility of Results, Neurofibrillary Tangles

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Clinical validity of Braak neuropathological staging in the oldest-old

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