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Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: correlation with Alzheimer's neuropathology
Ikonomovic MD, Mufson EJ, Wuu J, Cochran EJ, Bennett DA, DeKosky ST.. Journal of Alzheimer's disease : JAD, 2003-02-01
Topic: Amyloid, tau and blood-test diagnosis
Several recent studies indicate that activity of cholinergic enzymes in the cortex of people with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) are preserved. We correlated levels of hippocampal choline acetyltransferase (ChAT) activity with the extent of AD lesions in subjects from the Religious Order Study, including cases with no cognitive impairment (NCI), MCI, and with mild to moderate AD. Hippocampal ChAT activity levels were also determined in a group of end-stage AD patients who were enrolled in the University of Pittsburgh Alzheimer's Disease Research Center. MCI subjects were characterized with increased hippocampal ChAT activity. This elevation was no longer present in mild AD cases, which were not different from NCI subjects. Severe AD cases showed markedly depleted hippocampal ChAT levels. In NCI, MCI, and mild-moderate AD, there was a positive correlation between hippocampal ChAT activity levels and progression of neuritic plaque pathology in entorhinal cortex and hippocampus. A significant elevation of hippocampal ChAT in the MCI group was found selectively in the limbic (i.e., entorhinal-hippocampal, III/IV) Braak stages. We hypothesize that cholinergic changes in the hippocampus of MCI subjects reflect a compensatory response to the progressive denervation of the hippocampus by lost entorhinal cortex input. Moreover, the present findings suggest that the short-term memory loss observed in MCI is not caused by cholinergic deficits; it more likely relates to disrupted entorhinal-hippocampal connectivity.
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APA 7th
Ikonomovic, M. D., Mufson, E. J., Wuu, J., Cochran, E. J., Bennett, D. A., & DeKosky, S. T. (2003). Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: correlation with Alzheimer's neuropathology. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-2003-5106
Vancouver
Ikonomovic MD, Mufson EJ, Wuu J, Cochran EJ, Bennett DA, DeKosky ST. Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: correlation with Alzheimer's neuropathology. Journal of Alzheimer's disease : JAD. 2003. doi:10.3233/jad-2003-5106. PMID: 12590165.
BibTeX
@article{ikonomovic2003-12590165,
author = {Ikonomovic, M. D. and Mufson, E. J. and Wuu, J. and Cochran, E. J. and Bennett, D. A. and DeKosky, S. T.},
title = {{Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: correlation with Alzheimer's neuropathology}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2003},
doi = {10.3233/jad-2003-5106},
pmid = {12590165},
url = {https://doi.org/10.3233/jad-2003-5106}
}
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Key findings
- Several recent studies indicate that activity of cholinergic enzymes in the cortex of people with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) are preserved.
- A significant elevation of hippocampal ChAT in the MCI group was found selectively in the limbic (i.e., entorhinal-hippocampal, III/IV) Braak stages.
- Moreover, the present findings suggest that the short-term memory loss observed in MCI is not caused by cholinergic deficits; it more likely relates to disrupted entorhinal-hippocampal connectivity.
Why it matters
In brain tissue from the Religious Order Study, people with mild cognitive impairment had *higher*, not lower, activity of the hippocampal enzyme that makes acetylcholine (ChAT), but only at the intermediate "limbic" (Braak III/IV) stage of Alzheimer's pathology. The rise was gone in mild Alzheimer's and ChAT was markedly depleted in severe cases. The authors hypothesise that the rise is a compensatory response to lost entorhinal input, and that memory loss in MCI "more likely relates to disrupted entorhinal-hippocampal connectivity" than to a cholinergic deficit. No treatment was tested.
Study details
- Evidence strengthLow
How this study scored 42/100
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 (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 | 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 | 2003 — 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 136 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.4 citations a year over 25 year(s) since 2003 |
| Impact for its field and year | 3 / 6 | Cited 5.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Steven T. DeKosky: h-index 132 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Pittsburgh: institution h-index 1,470 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12590165) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 42 / 100 | — |
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