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Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence
Hshieh TT, Fong TG, Marcantonio ER, Inouye SK.. The journals of gerontology. Series A, Biological sciences and medical sciences, 2008-07-01
Topic: Brain proteins, microglia and lab models
Deficits in cholinergic function have been postulated to cause delirium and cognitive decline. This review examines current understanding of the cholinergic deficiency hypothesis in delirium by synthesizing evidence on potential pathophysiological pathways. Acetylcholine synthesis involves various precursors, enzymes, and receptors, and dysfunction in these components can lead to delirium. Insults to the brain, like ischemia and immunological stressors, can precipitously alter acetylcholine levels. Imbalances between cholinergic and other neurotransmitter pathways may result in delirium. Furthermore, genetic, enzymatic, and immunological overlaps exist between delirium and dementia related to the cholinergic pathway. Important areas for future research include identifying biomarkers, determining genetic contributions, and evaluating response to cholinergic drugs in delirium. Understanding how the cholinergic pathway relates to delirium may yield innovative approaches in the diagnosis, prevention, and treatment of this common, costly, and morbid condition.
Key findings
- Imbalances between cholinergic and other neurotransmitter pathways may result in delirium.
Why it matters
This review examines the cholinergic deficiency hypothesis in delirium, proposing that imbalances between cholinergic and other neurotransmitter pathways may result in delirium. It suggests understanding this pathway may yield approaches to diagnosis, prevention, and treatment of delirium, not Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 52/100
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 (The journals of gerontology. Series A, Biological sciences and medical sciences) |
| Journal's citation record | 3 / 4 | The Journals of Gerontology Series A: journal h-index 274 (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 | 2008 — within 20 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 553 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 27.6 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 4 / 6 | Cited 15.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 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 | 4 / 4 | Last-listed author Sharon K. Inouye: h-index 118 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18693233) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1093/gerona/63.7.764
- PubMed: 18693233
- Original source →
- Free full text: The Journals of Gerontology Series A →
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. Check the citation against the original before you use it.
APA 7th
Hshieh, T. T., Fong, T. G., Marcantonio, E. R., & Inouye, S. K. (2008). Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. The journals of gerontology. Series A, Biological sciences and medical sciences. https://doi.org/10.1093/gerona/63.7.764
Vancouver
Hshieh TT, Fong TG, Marcantonio ER, Inouye SK. Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. The journals of gerontology. Series A, Biological sciences and medical sciences. 2008. doi:10.1093/gerona/63.7.764. PMID: 18693233.
BibTeX
@article{hshieh2008-18693233,
author = {Hshieh, T. T. and Fong, T. G. and Marcantonio, E. R. and Inouye, S. K.},
title = {{Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence}},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
year = {2008},
doi = {10.1093/gerona/63.7.764},
pmid = {18693233},
url = {https://doi.org/10.1093/gerona/63.7.764}
}
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