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Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease
Garcia-Alloza M, Gil-Bea FJ, Gil-Bea FJ, Diez-Ariza M, Chen CP, Francis PT, Lasheras B, Ramirez MJ.. Neuropsychologia, 2005-01-01
Topic: Amyloid, tau and blood-test diagnosis
Neuropsychiatric symptoms seen in Alzheimer's disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in post-mortem frontal and temporal cortex from 22 AD patients who had been prospectively assessed with the Mini-Mental State examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD including aggressive behavior, overactivity, depression and psychosis.
Key findings
- Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD.
- Cholinergic and serotonergic functions were assessed in post-mortem frontal and temporal cortex from 22 AD patients who had been prospectively assessed with the Mini-Mental State examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD including aggressive behavior, overactivity, depression and psychosis.
- Not only cholinergic deficits, but also the cholinacetyltransferase/serotonin ratio significantly correlated with final MMSE score both in frontal and temporal cortex.
- In addition, decreases in cholinergic function correlated with the aggressive behavior factor, supporting a dual role for the cholinergic system in cognitive and non-cognitive disturbances associated to AD.
Why it matters
In brain tissue from 22 deceased Alzheimer's patients, an imbalance between the cholinergic and serotonergic systems was related to cognitive and behavioral symptoms. This is a post-mortem study of how symptoms arise and does not test any treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 44/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuropsychologia) |
| Journal's citation record | 3 / 4 | Neuropsychologia: journal h-index 321 (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 | 2005 — older than 20 years, still counted |
| 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 244 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.6 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 3 / 6 | Cited 4.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 43 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author María Javier Ramírez: h-index 52 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | King's College London: institution h-index 1,348 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15707619) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 44 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.neuropsychologia.2004.06.007
- PubMed: 15707619
- Original source →
- Free full text: Deposito Adademico Digital Universidad De Navarra (University of Navarra) →
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
Garcia-Alloza, M., Gil-Bea, F. J., Diez-Ariza, M., Chen, C. P., Francis, P. T., Lasheras, B., et al. (2005). Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease. Neuropsychologia. https://doi.org/10.1016/j.neuropsychologia.2004.06.007
Vancouver
Garcia-Alloza M, Gil-Bea FJ, Diez-Ariza M, Chen CP, Francis PT, Lasheras B, et al. Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease. Neuropsychologia. 2005. doi:10.1016/j.neuropsychologia.2004.06.007. PMID: 15707619.
BibTeX
@article{garciaalloza2005-15707619,
author = {Garcia-Alloza, M. and Gil-Bea, F. J. and Diez-Ariza, M. and Chen, C. P. and Francis, P. T. and Lasheras, B. and Ramirez, M. J.},
title = {{Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease}},
journal = {Neuropsychologia},
year = {2005},
doi = {10.1016/j.neuropsychologia.2004.06.007},
pmid = {15707619},
url = {https://doi.org/10.1016/j.neuropsychologia.2004.06.007}
}
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