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Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment
Robert D. Terry, Eliezer Masliah, David P. Salmon, Nelson Butters, Richard M. DeTeresa, Robert Hill, Lawrence A. Hansen, Robert Katzman. Annals of Neurology, 1991-10-01
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of 15 patients with Alzheimer's disease and 9 neuropathologically normal subjects. The statistical data show only weak correlations between psychometric indices and plaques and tangles, but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique reveals very powerful correlations with all three psychological assays. Multivariate analysis by stepwise regression produced a model including midfrontal and inferior parietal synapse density, plus inferior parietal plaque counts with a correlation coefficient of 0.96 for Mattis's Dementia Rating Scale. Plaque density contributed only 26% of that strength.
What this study adds
Evidence grade: Low
The record lists 15 participants. In this study of 15 Alzheimer's disease patients and 9 normal subjects, synapse density in the neocortex showed very strong correlations with cognitive tests, while plaques and tangles showed only weak correlations. It suggests synapse loss is a major correlate of cognitive impairment in Alzheimer's disease.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R. M., Hill, R., et al. (1991). Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Annals of Neurology. https://doi.org/10.1002/ana.410300410
Vancouver
Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa RM, Hill R, et al. Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Annals of Neurology. 1991. doi:10.1002/ana.410300410. PMID: 1789684.
BibTeX
@article{terry1991-1789684,
author = {Terry, Robert D. and Masliah, Eliezer and Salmon, David P. and Butters, Nelson and DeTeresa, Richard M. and Hill, Robert and Hansen, Lawrence A. and Katzman, Robert},
title = {{Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment}},
journal = {Annals of Neurology},
year = {1991},
doi = {10.1002/ana.410300410},
pmid = {1789684},
url = {https://doi.org/10.1002/ana.410300410}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of 15 patients with Alzheimer's disease and 9 neuropathologically normal subjects.
- The statistical data show only weak correlations between psychometric indices and plaques and tangles, but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique reveals very powerful correlations with all three psychological assays.
- Multivariate analysis by stepwise regression produced a model including midfrontal and inferior parietal synapse density, plus inferior parietal plaque counts with a correlation coefficient of 0.96 for Mattis's Dementia Rating Scale.
- Plaque density contributed only 26% of that strength.
Why it matters
In this study of 15 Alzheimer's disease patients and 9 normal subjects, synapse density in the neocortex showed very strong correlations with cognitive tests, while plaques and tangles showed only weak correlations. It suggests synapse loss is a major correlate of cognitive impairment in Alzheimer's disease.
Study details
- Participants15
- Evidence strengthLow
How this study scored 62/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of Neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (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 | 1991 — older than 20 years, still counted |
| Sample size | 1 / 4 | 15 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 4,408 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 119.1 citations a year over 37 year(s) since 1991 |
| Impact for its field and year | 6 / 6 | Cited 44.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 5 / 6 | Cited by 168 other studies in this library |
| Still being cited | 4 / 4 | Cited 472 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Robert Katzman: h-index 50 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 1789684) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 62 / 100 | — |
What each of these 20 components measures, and what this score is not →
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