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Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer's Disease
Ehrenberg AJ, Suemoto CK, França Resende EP, Petersen C, Leite REP, Rodriguez RD, Ferretti-Rebustini REL, You M et al.. Journal of Alzheimer's disease : JAD, 2018-01-01
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Clarifying the relationships between neuropsychiatric symptoms and Alzheimer's disease (AD)-related pathology may open avenues for effective treatments. Here, we investigate the odds of developing neuropsychiatric symptoms across increasing burdens of neurofibrillary tangle and amyloid-β pathology. Participants who passed away between 2004 and 2014 underwent comprehensive neuropathologic evaluation at the Biobank for Aging Studies from the Faculty of Medicine at the University of São Paulo. Postmortem interviews with reliable informants were used to collect information regarding neuropsychiatric and cognitive status. Of 1,092 cases collected, those with any non-Alzheimer pathology were excluded, bringing the cohort to 455 cases. Braak staging was used to evaluate neurofibrillary tangle burden, and the CERAD neuropathology score was used to evaluate amyloid-β burden. The 12-item neuropsychiatric inventory was used to evaluate neuropsychiatric symptoms and CDR-SOB score was used to evaluate dementia status. In Braak I/II, significantly increased odds were detected for agitation, anxiety, appetite changes, depression, and sleep disturbances, compared to controls. Increased odds of agitation continue into Braak III/IV. Braak V/VI is associated with higher odds for delusions. No increased odds for neuropsychiatric symptoms were found to correlate with amyloid-β pathology. Increased odds of neuropsychiatric symptoms are associated with early neurofibrillary tangle pathology, suggesting that subcortical neurofibrillary tangle accumulation with minimal cortical pathology is sufficient to impact quality of life and that neuropsychiatric symptoms are a manifestation of AD biological processes.
What this study adds
Evidence grade: Moderate
This autopsy study found that early neurofibrillary tangle pathology was linked to higher odds of agitation, anxiety, appetite changes, depression, and sleep disturbances, while amyloid-beta pathology showed no such link. It suggests these psychiatric symptoms may reflect underlying tangle pathology, but it does not test any treatment or prevention.
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
Ehrenberg, A. J., Suemoto, C. K., França Resende, E. P., Petersen, C., Leite, R. E. P., Rodriguez, R. D., et al. (2018). Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer's Disease. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-180688
Vancouver
Ehrenberg AJ, Suemoto CK, França Resende EP, Petersen C, Leite REP, Rodriguez RD, et al. Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer's Disease. Journal of Alzheimer's disease : JAD. 2018. doi:10.3233/jad-180688. PMID: 30223398.
BibTeX
@article{ehrenberg2018-30223398,
author = {Ehrenberg, A. J. and Suemoto, C. K. and França Resende, E. P. and Petersen, C. and Leite, R. E. P. and Rodriguez, R. D. and Ferretti-Rebustini, R. E. L. and You, M. and others},
title = {{Neuropathologic Correlates of Psychiatric Symptoms in Alzheimer's Disease}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2018},
doi = {10.3233/jad-180688},
pmid = {30223398},
url = {https://doi.org/10.3233/jad-180688}
}
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Key findings
- In Braak I/II, significantly increased odds were detected for agitation, anxiety, appetite changes, depression, and sleep disturbances, compared to controls.
- Braak V/VI is associated with higher odds for delusions.
- Increased odds of neuropsychiatric symptoms are associated with early neurofibrillary tangle pathology, suggesting that subcortical neurofibrillary tangle accumulation with minimal cortical pathology is sufficient to impact quality of life and that neuropsychiatric symptoms are a manifestation of AD biological processes.
Why it matters
This autopsy study found that early neurofibrillary tangle pathology was linked to higher odds of agitation, anxiety, appetite changes, depression, and sleep disturbances, while amyloid-beta pathology showed no such link. It suggests these psychiatric symptoms may reflect underlying tangle pathology, but it does not test any treatment or prevention.
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Study details
- Evidence strengthModerate
How this study scored 53/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 214 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.4 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 12.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 3 / 4 | Cited 87 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Lea T. Grinberg: h-index 97 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30223398) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
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