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Neuropsychiatric symptoms and progression to pathologically confirmed Alzheimer’s disease
Sergio Fernandez Sharif, Dylan X. Guan, Tamara S. Bodnar, Jeffrey T. Joseph, Henrik Zetterberg, Eric Edward Smith, Zahinoor Ismail. Brain, 2025-04-25
Topic: Amyloid, tau and blood-test diagnosis
Whether or not neuropsychiatric symptoms (NPS) in advance of dementia are associated with Alzheimer's disease (AD) and/or other neurodegenerative dementias remains to be determined. Here, in older adults without dementia at baseline, we examined whether post-mortem AD and other neurodegenerative pathologies were associated with MBI in the 5 years before death. No significant associations were seen for LBD pathology, even among AD+ participants. There were no significant differences in the levels of LBD or transactive response DNA-binding protein 43 in those with MBI in comparison to no MBI. The progression rate was higher in mild cognitive impairment , but the effect of MBI on progression was greater in normal cognition (hazard ratio: 3.05, CI: 1.37-6.80, P < 0.01) versus mild cognitive impairment (hazard ratio: 1.93, CI: 1.51-2.47, P < 0.01). Antecedent MBI was strongly associated with AD pathology but not with other neurodegenerative dementias.
Key findings
- Whether or not neuropsychiatric symptoms (NPS) in advance of dementia are associated with Alzheimer's disease (AD) and/or other neurodegenerative dementias remains to be determined.
- Here, in older adults without dementia at baseline, we examined whether post-mortem AD and other neurodegenerative pathologies were associated with MBI in the 5 years before death.
- No significant associations were seen for LBD pathology, even among AD+ participants.
- There were no significant differences in the levels of LBD or transactive response DNA-binding protein 43 in those with MBI in comparison to no MBI.
- The progression rate was higher in mild cognitive impairment , but the effect of MBI on progression was greater in normal cognition (hazard ratio: 3.05, CI: 1.37-6.80, P < 0.01) versus mild cognitive impairment (hazard ratio: 1.93, CI: 1.51-2.47, P < 0.01).
Why it matters
This study found that mild behavioral impairment before death was strongly associated with Alzheimer's disease pathology but not with other neurodegenerative dementias, and no significant associations were seen for Lewy body disease pathology. It examines associations with post-mortem pathology and does not test any treatment, cure, or prevention.
Study details
- Participants1,016
- Effect size48.7%; 51.4%; 88.4%
- Evidence strengthLow
How this study scored 60/100
Published in a leading specialty journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,016 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 3 / 7 | Cited 19 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 12.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Zahinoor Ismail: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40279515) |
| Free to read | 2 / 2 | Free to read |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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 7 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.
APA 7th
Sharif, S. F., Guan, D. X., Bodnar, T. S., Joseph, J. T., Zetterberg, H., Smith, E. E., et al. (2025). Neuropsychiatric symptoms and progression to pathologically confirmed Alzheimer’s disease. Brain. https://doi.org/10.1093/brain/awaf156
Vancouver
Sharif SF, Guan DX, Bodnar TS, Joseph JT, Zetterberg H, Smith EE, et al. Neuropsychiatric symptoms and progression to pathologically confirmed Alzheimer’s disease. Brain. 2025. doi:10.1093/brain/awaf156. PMID: 40279515.
BibTeX
@article{sharif2025-40279515,
author = {Sharif, Sergio Fernandez and Guan, Dylan X. and Bodnar, Tamara S. and Joseph, Jeffrey T. and Zetterberg, Henrik and Smith, Eric Edward and Ismail, Zahinoor},
title = {{Neuropsychiatric symptoms and progression to pathologically confirmed Alzheimer’s disease}},
journal = {Brain},
year = {2025},
doi = {10.1093/brain/awaf156},
pmid = {40279515},
url = {https://doi.org/10.1093/brain/awaf156}
}
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