Cited by 106Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Morphological substrates of cognitive decline in nonagenarians and centenarians: A new paradigm?

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Imhof, Anouk, Kövari, Enikö, von Gunten, Armin, Gold, Gabriel, Rivara, Claire-Bénédicte, Herrmann, François R., Hof, Patrick R., Bouras, Constantin +1 more·2007·Journal of the Neurological Sciences

Abstract

Brain aging is characterized by the formation of neurofibrillary tangles (NFT) and senile plaques (SP) in both cognitively intact individuals and patients with Alzheimer's disease (AD). The ubiquitous presence of these lesions and the steady increase of the prevalence of dementia up to 85 years have strongly supported a continuum between normal brain aging and AD. In this context, the study of nonagenarians and centenarians could provide key informations about the characteristics of extreme aging. We provide here a detailed review of currently available neuropathological data in very old individuals and critically discuss the patterns of NFT, SP and neuronal loss distribution as a function of age. In younger cohorts, NFTs are usually restricted to hippocampal formation, whereas clinical signs of dementia appear when temporal neocortex is involved. SPs would not be a specific marker of cognitive impairment as no correlation was found between their quantitative distribution and AD severity. The low rate of AD lesions even in severe AD as well as the weakness of clinicopathological correlations reported in the oldest-old indicate that AD pathology is not a mandatory phenomenon of increasing chronological age. Our recent stereological observations of hippocampal microvasculature in oldest-old cases challenge the traditional lesional model by revealing that mean capillary diameters is an important structural determinant of cognition in this age group.

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Crossref · 10.1016/j.jns.2007.01.025

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  • In brains from cognitively intact subjects, hippocampal CA1 neuron counts do not correlate with age.

    “In brains from cognitively intact subjects, hippocampal CA1 neuron counts do not correlate with age [47–49].”

    From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [49]

  • Not all studies are in agreement that the prevalence of high NP and high NFT pathologic diagnosis levels off in the oldest old.

    “However, not all studies are in agreement on this point (185, 186); these “survivors” represent a small fraction of the human population with underrepresentation of APOE ε4 allele (187).”

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Authors
Imhof, A., Kövari, E., von Gunten, A., Gold, G., Rivara, C.-B., Herrmann, F. R., Hof, P. R., Bouras, C., & Giannakopoulos, P.
Affiliations
  • University of Geneva (CH)
  • Icahn School of Medicine at Mount Sinai (US)
Venue
Journal of the Neurological Sciences
Publisher
Elsevier BV
Published
2007-06
Volume
257
Issue
1-2
Pages
72-79
ISSN
0022-510X (ISSN-L)
OpenAlex
W2019428673
Cited by
106
References
97
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 2 · 2020: 5 · 2019: 8 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 3 · 2012: 8
FWCI
1.03
Type
journal article
Language
en
Open access
Locations
  • Journal of the Neurological Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion)
Funders
National Institute on Aging (AG-02219, AG 05138, P50AG005138, P01AG002219)
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 › Neurological Disease Mechanisms and Treatments
Keywords
cognitive decline, nonagenarians, centenarians, brain aging, Alzheimer's disease, neurofibrillary tangles, amyloid plaques, neuronal loss, capillary diameter, oldest old, clinicopathological correlation, dementia
MeSH terms
Aged, 80 and over, Aging, Alzheimer Disease, Brain, Cerebral Arteries, Cognition Disorders, Hippocampus, Humans, Neurofibrillary Tangles, Disease Progression, Plaque, Amyloid

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