Role of the neuropathology of Alzheimer disease in dementia in the oldest-old
Open accessAbstract
BACKGROUND: Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) in the brain, especially in the hippocampus, entorhinal cortex, and isocortex, are hallmark lesions of Alzheimer disease and dementia in the elderly. However, this association has not been extensively studied in the rapidly growing population of the very old. OBJECTIVE: To assess the relationship between estimates of cognitive function and NP and NFT pathologic conditions in 317 autopsied persons aged 60 to 107 years. DESIGN: We studied the relationship between severity of dementia and the density of these characteristic lesions of Alzheimer disease in young-old, middle-old, and oldest-old persons. The relationship of the severity of dementia as measured by the Clinical Dementia Rating scale to the density of NPs and NFTs was then assessed in each age group. PARTICIPANTS: Three hundred seventeen brains of persons aged 60 years and older were selected to have either no remarkable neuropathological lesions or only NP and NFT lesions. Brains with any other neuropathological conditions, either alone or in addition to Alzheimer disease findings, were excluded. The study cohort was then stratified into the youngest quartile (aged 60-80 years), middle 2 quartiles (aged 81-89 years), and oldest quartile (aged 90-107 years). RESULTS: While the density of NPs and NFTs rose significantly by more than 10-fold as a function of the severity of dementia in the youngest-old group, significant increases in the densities of NPs and NFTs were absent in the brains of the oldest-old. This lack of difference in the densities of NPs and NFTs was due to reduced lesion densities in the brains of oldest-old persons with dementia rather than to increased density of these lesions in the brains of nondemented oldest-old persons. CONCLUSIONS: These findings suggest that the neuropathological features of dementia in the oldest-old are not the same as those of cognitively impaired younger-old persons and compel a vigorous search for neuropathological indices of dementia in this most rapidly growing segment of the elderly population.
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The poor correlation between pathology and cognition may be more pronounced in the oldest-old.
“This relatively poor correlation may become even more pronounced in the oldest-old (Ewbank and Arnold, 2009,Haroutunian, et al., 2008).”
From Cellular, synaptic, and biochemical features of resilient cognition in Alzheimer’s disease (2013) · cites this paper as Haroutunian, et al., 2008
In contrast to the increased prevalence of clinical dementia with advanced age, the prevalence of cases with high NP and high NFT pathologic diagnosis at autopsy seems to level off in the oldest old according to multiple autopsy series.
“In contrast to the increased prevalence of clinical dementia with advanced age, the prevalence of cases with high NP and high NFT pathologic diagnosis at autopsy seems to level off in the oldest old according to multiple autopsy series (154, 168-172).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [170]
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References 43 · Cited by 154
- Authors
- Haroutunian, V., Schnaider-Beeri, M., Schmeidler, J., Wysocki, M., Purohit, D. P., Perl, D. P., Libow, L. S., Lesser, G. T., Maroukian, M., & Grossman, H. T.
- Affiliations
- James J. Peters VA Medical Center (US)
- Mount Sinai Hospital (US)
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2008-09-01
- Volume
- 65
- Issue
- 9
- Pages
- 1211-7
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC3071251
- OpenAlex
- W2084585586
- Cited by
- 154
- References
- 43
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 9 · 2019: 11 · 2018: 6 · 2017: 7 · 2016: 9 · 2015: 6 · 2014: 6 · 2013: 16 · 2012: 14
- FWCI
- 11.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG-02219, P01AG002219)
- National Center for Research Resources (M01RR000071, M01-RR-00071)
- 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
- Alzheimer's disease, neuropathology, neuritic plaques, neurofibrillary tangles, Clinical Dementia Rating, lesion density, cognitive impairment, aging, hippocampus, entorhinal cortex
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Dementia, Female, Humans, Male, Middle Aged, Cohort Studies, Neurofibrillary Tangles, Plaque, Amyloid
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