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Alzheimer-typical temporo-parietal atrophy and hypoperfusion are associated with a more significant cholinergic impairment in amnestic neurodegenerative syndromes
Nils Richter, Laura Breidenbach, Maximilian H.T. Schmieschek, Wolf‐Dieter Heiss, Gereon R. Fink, Oezguer A. Onur. Journal of Alzheimer s Disease, 2025-03-21
Topic: Brain proteins, microglia and lab models
BackgroundTo date, cholinomimetics remain central in the pharmacotherapy of Alzheimer's disease (AD) dementia. However, postmortem investigations indicate that the AD-typical progressive amnestic syndrome may also result from predominantly limbic non-AD neuropathology such as TDP-43 proteinopathy and argyrophilic grain disease. Experimental evidence links a beneficial response to cholinomimetics in early AD to reduced markers of cholinergic neurotransmission. However, the cholinergic impairment varies among patients with a clinical AD presentation, likely due to non-AD (co)-pathologies.ObjectiveThis study examines whether AD-typical atrophy and hypoperfusion can provide information about the cholinergic system in clinically diagnosed AD.MethodsThirty-two patients with amnestic mild cognitive impairment or mild dementia due to AD underwent positron emission tomography (PET) with the tracer N-methyl-4-piperidyl-acetate (MP4A) to estimate acetylcholinesterase (AChE) activity, neurological examinations, cerebral magnetic resonance imaging (MRI) and neuropsychological assessment. The 'cholinergic deficit' was computed as the deviation of AChE activity from cognitively normal controls across the cerebral cortex and correlated gray matter (GM) and perfusion of temporo-parietal cortices typically affected by AD and basal forebrain (BF) GM.ResultsTemporo-parietal perfusion and GM, as well as the inferior temporal to medial temporal ratio of perfusion correlated negatively with the 'cholinergic deficit'. A smaller Ch4p area of the BF was associated with a more significant 'cholinergic deficit', albeit to a lesser degree than cortical measures.ConclusionsIn clinically diagnosed AD, temporo-parietal GM and perfusion are more closely associated with the 'cholinergic deficit' than BF volumes, making them possible markers for cholinergic treatment response in amnestic neurodegeneration.
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APA 7th
Richter, N., Breidenbach, L., Schmieschek, M. H., Heiss, W., Fink, G. R., & Onur, O. A. (2025). Alzheimer-typical temporo-parietal atrophy and hypoperfusion are associated with a more significant cholinergic impairment in amnestic neurodegenerative syndromes. Journal of Alzheimer s Disease. https://doi.org/10.1177/13872877251324080
Vancouver
Richter N, Breidenbach L, Schmieschek MH, Heiss W, Fink GR, Onur OA. Alzheimer-typical temporo-parietal atrophy and hypoperfusion are associated with a more significant cholinergic impairment in amnestic neurodegenerative syndromes. Journal of Alzheimer s Disease. 2025. doi:10.1177/13872877251324080. PMID: 40116674.
BibTeX
@article{richter2025-40116674,
author = {Richter, Nils and Breidenbach, Laura and Schmieschek, Maximilian H.T. and Heiss, Wolf‐Dieter and Fink, Gereon R. and Onur, Oezguer A.},
title = {{Alzheimer-typical temporo-parietal atrophy and hypoperfusion are associated with a more significant cholinergic impairment in amnestic neurodegenerative syndromes}},
journal = {Journal of Alzheimer s Disease},
year = {2025},
doi = {10.1177/13872877251324080},
pmid = {40116674},
url = {https://doi.org/10.1177/13872877251324080}
}
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.
Key findings
- However, postmortem investigations indicate that the AD-typical progressive amnestic syndrome may also result from predominantly limbic non-AD neuropathology such as TDP-43 proteinopathy and argyrophilic grain disease.
- A smaller Ch4p area of the BF was associated with a more significant 'cholinergic deficit', albeit to a lesser degree than cortical measures.ConclusionsIn clinically diagnosed AD, temporo-parietal GM and perfusion are more closely associated with the 'cholinergic deficit' than BF volumes, making them possible markers for cholinergic treatment response in amnestic neurodegeneration.
Why it matters
In 32 patients with amnestic mild cognitive impairment or mild dementia due to Alzheimer's disease, temporo-parietal gray matter and perfusion were more closely associated with cholinergic deficit than basal forebrain measures. The authors note that the amnestic syndrome can also result from non-Alzheimer's neuropathology such as TDP-43 proteinopathy and argyrophilic grain disease.
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Study details
- Evidence strengthLow
How this study scored 38/100
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) |
| 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 | 4 / 5 | 2025 — within 3 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 | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Oezguer A. Onur: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Cologne: institution h-index 879 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40116674) |
| Free to read | 2 / 2 | Free to read |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1177/13872877251324080
- PubMed: 40116674
- Original source →
- Free full text: Journal of Alzheimer s Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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