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Neuropathology of cognitively normal elderly
Knopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, Smith GE, Dickson DW et al.. Journal of neuropathology and experimental neurology, 2003-11-01
Topic: Risk, prevention and care in population studies
Despite general agreement about the boundaries of Alzheimer disease (AD), establishing a maximum limit for Alzheimer-type pathology in cognitively intact individuals might aid in defining more precisely the point at which Alzheimer pathology becomes clinically relevant. In this study, we examined the neuropathological changes in the brains of 39 longitudinally followed. cognitively normal elderly individuals (24 women, 15 men; age range 74-95, median 85 years). Neuropathological changes of the Alzheimer type were quantified by determining neurofibrillary tangle (NFT) staging by the method of Braak and Braak and by quantification of the abundance of diffuse, cored, and neuritic plaque burden using the scheme developed by the Consortium to Establish a Registry for Alzheimer Disease (CERAD). Vascular, Lewy body, and argyrophilic grain pathology were also assessed. We found 34 subjects (87%) with a Braak stage <IV; 32 subjects (82%) with less than moderate numbers of cored plaques and 37 subjects (95%) with less than moderate numbers of tau-positive neuritic plaques. Many subjects had moderate or frequent diffuse plaques (n = 19, 49%). By the National Institute on Aging-Reagan Institute (NIA-RI) criteria, none of our cases met criteria for high "likelihood" of AD. Four met NIA-RI criteria for intermediate "likelihood." Seven cases met CERAD criteria for possible AD. Nineteen met Khachaturian criteria for AD. Only 1 subject had neocortical Lewy bodies. Small, old infarcts were common, but no subjects had more than 2 of these and none had a single large infarction. Thus, the majority of individuals who are cognitively normal near the time of their death have minimal amounts of tau-positive neuritic pathology (Braak stage <IV and neuritic plaques <6 per x100 field in the most affected neocortical region). The few subjects with more severe AD pathology can be expected based on incidence rates of AD in the very elderly.
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APA 7th
Knopman, D. S., Parisi, J. E., Salviati, A., Floriach-Robert, M., Boeve, B. F., Ivnik, R. J., et al. (2003). Neuropathology of cognitively normal elderly. Journal of neuropathology and experimental neurology. https://doi.org/10.1093/jnen/62.11.1087
Vancouver
Knopman DS, Parisi JE, Salviati A, Floriach-Robert M, Boeve BF, Ivnik RJ, et al. Neuropathology of cognitively normal elderly. Journal of neuropathology and experimental neurology. 2003. doi:10.1093/jnen/62.11.1087. PMID: 14656067.
BibTeX
@article{knopman2003-14656067,
author = {Knopman, D. S. and Parisi, J. E. and Salviati, A. and Floriach-Robert, M. and Boeve, B. F. and Ivnik, R. J. and Smith, G. E. and Dickson, D. W. and others},
title = {{Neuropathology of cognitively normal elderly}},
journal = {Journal of neuropathology and experimental neurology},
year = {2003},
doi = {10.1093/jnen/62.11.1087},
pmid = {14656067},
url = {https://doi.org/10.1093/jnen/62.11.1087}
}
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Key findings
- We found 34 subjects (87%) with a Braak stage <IV; 32 subjects (82%) with less than moderate numbers of cored plaques and 37 subjects (95%) with less than moderate numbers of tau-positive neuritic plaques.
Why it matters
Brains from 39 people aged 74–95 who were cognitively normal near death mostly showed little tangle or neuritic-plaque damage: 87% had a Braak stage below IV and 95% had fewer than moderate neuritic plaques, although 49% had moderate or frequent diffuse plaques. How many counted as "Alzheimer's" depended heavily on the criteria used — none met NIA-Reagan "high likelihood", 7 met CERAD "possible AD" and 19 met Khachaturian criteria. It is a small autopsy series with no dementia comparison group, so it describes what normal ageing brains can contain rather than setting a diagnostic cut-off, and it tests no treatment.
Study details
- Participants19
- Evidence strengthLow
How this study scored 56/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuropathology and experimental neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2003 — older than 20 years, still counted |
| Sample size | 1 / 4 | 19 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 675 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 27.0 citations a year over 25 year(s) since 2003 |
| Impact for its field and year | 4 / 6 | Cited 11.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 81 other studies in this library |
| Still being cited | 3 / 4 | Cited 60 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Ronald Carl Petersen: h-index 209 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 14656067) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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