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Lewy body pathology exacerbates brain hypometabolism and cognitive decline in Alzheimer's disease
Collij LE, Mastenbroek SE, Mattsson-Carlgren N, Strandberg O, Smith R, Janelidze S, Palmqvist S, Ossenkoppele R, Hansson O. Nature Communications, 2024-09-14
Topic: Brain proteins, microglia and lab models
Identifying concomitant Lewy body (LB) pathology through seed amplification assays (SAA) might enhance the diagnostic and prognostic work-up of Alzheimer's disease (AD) in clinical practice and trials. This study examined whether LB pathology exacerbates AD-related disease progression in 795 cognitively impaired individuals (Mild Cognitive Impairment and dementia) from the longitudinal multi-center observational ADNI cohort. Participants were on average 75 years of age (SD = 7.89), 40.8% were female, 184 (23.1%) had no biomarker evidence of AD/LB pathology, 39 (4.9%) had isolated LB pathology (AD-LB+), 395 (49.7%) had only AD pathology (AD+LB-), and 177 (22.3%) had both pathologies (AD+LB+). The AD+LB+ group showed worst baseline performance for most cognitive outcomes and compared to the AD+LB- group faster global cognitive decline and more cortical hypometabolism, particularly in posterior brain regions. Neuropathological examination (n = 61) showed high sensitivity (26/27, 96.3%) and specificity (27/28, 96.4%) of the SAA-test. We showed that co-existing LB-positivity exacerbates cognitive decline and cortical brain hypometabolism in AD. In vivo LB pathology detection could enhance prognostic evaluations in clinical practice and could have implications for clinical AD trial design.
Key findings
- The AD+LB+ group showed worst baseline performance for most cognitive outcomes and compared to the AD+LB- group faster global cognitive decline and more cortical hypometabolism, particularly in posterior brain regions.
- We showed that co-existing LB-positivity exacerbates cognitive decline and cortical brain hypometabolism in AD.
Why it matters
Among 795 cognitively impaired participants, those with both Alzheimer's disease and Lewy body pathology showed worse baseline cognition and faster global cognitive decline and cortical hypometabolism than those with only Alzheimer's pathology. The authors say that detecting Lewy body pathology in vivo could enhance prognostic evaluations and have implications for clinical trial design.
Study details
- Study designcohort
- Participants795
- Effect size22.3% of cognitively impaired participants had co-existing AD and Lewy body pathology; SAA sensitivity 96.3%, specificity 96.4%
- Evidence strengthModerate
Limitations
ADNI is a research cohort that is whiter, more educated and healthier than the general population; observational; only 61 autopsy confirmations.
How this study scored 69/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 68 of the 98 points we could judge it on, which is 69 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 795 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 | 4 / 7 | Cited 46 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.5 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 4 / 6 | Cited 12.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 2 / 4 | Cited 46 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Oskar Hansson: h-index 148 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Lund University: institution h-index 1,119 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39277604) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 68 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 68 of the 98 points we could judge it on is 69 out of 100. |
| Total | 69 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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 9 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
Collij, L. E., Mastenbroek, S. E., Mattsson-Carlgren, N., Strandberg, O., Smith, R., Janelidze, S., et al. (2024). Lewy body pathology exacerbates brain hypometabolism and cognitive decline in Alzheimer's disease. Nature Communications. https://doi.org/10.1038/s41467-024-52299-1
Vancouver
Collij LE, Mastenbroek SE, Mattsson-Carlgren N, Strandberg O, Smith R, Janelidze S, et al. Lewy body pathology exacerbates brain hypometabolism and cognitive decline in Alzheimer's disease. Nature Communications. 2024. doi:10.1038/s41467-024-52299-1. PMID: 39277604.
BibTeX
@article{collij2024-39277604,
author = {Collij, L. E. and Mastenbroek, S. E. and Mattsson-Carlgren, N. and Strandberg, O. and Smith, R. and Janelidze, S. and Palmqvist, S. and Ossenkoppele, R. and Hansson, O.},
title = {{Lewy body pathology exacerbates brain hypometabolism and cognitive decline in Alzheimer's disease}},
journal = {Nature Communications},
year = {2024},
doi = {10.1038/s41467-024-52299-1},
pmid = {39277604},
url = {https://doi.org/10.1038/s41467-024-52299-1}
}
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