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A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies
Nalls MA, Duran R, Lopez G, Kurzawa-Akanbi M, McKeith IG, Chinnery PF, Morris CM, Theuns J et al.. JAMA neurology, 2013-06-01
Topic: Brain proteins, microglia and lab models
Importance While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders. Objective To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB). DESIGN We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity. Setting Eleven centers from sites around the world performing genotyping. Participants Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity. Main outcome measures Frequency of GBA1 mutations in cases and controls. RESULTS We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78-14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53-15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P Conclusions and relevance Mutations in GBA1 are a significant risk factor for DLB. GBA1 mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease.
Key findings
- Importance While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders.
- RESULTS We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78-14.88).
- The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P Conclusions and relevance Mutations in GBA1 are a significant risk factor for DLB.
Why it matters
This multicenter study found that mutations in the GBA1 gene were significantly associated with dementia with Lewy bodies and with Parkinson's disease with dementia. This identifies a genetic risk factor for these conditions but does not provide a treatment, cure or prevention.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 71/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — 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 | A review of other studies — randomisation is not credited here |
| Times cited | 6 / 7 | Cited 440 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 29.3 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 5 / 6 | Cited 21.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 3 / 4 | Cited 81 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ellen Sidransky: h-index 74 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 20 institution(s) in 7 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23588557) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 71 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2013.1925
- PubMed: 23588557
- Original source →
- Free full text: PubMed Central →
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Nalls, M. A., Duran, R., Lopez, G., Kurzawa-Akanbi, M., McKeith, I. G., Chinnery, P. F., et al. (2013). A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies. JAMA neurology. https://doi.org/10.1001/jamaneurol.2013.1925
Vancouver
Nalls MA, Duran R, Lopez G, Kurzawa-Akanbi M, McKeith IG, Chinnery PF, et al. A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies. JAMA neurology. 2013. doi:10.1001/jamaneurol.2013.1925. PMID: 23588557.
BibTeX
@article{nalls2013-23588557,
author = {Nalls, M. A. and Duran, R. and Lopez, G. and Kurzawa-Akanbi, M. and McKeith, I. G. and Chinnery, P. F. and Morris, C. M. and Theuns, J. and others},
title = {{A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies}},
journal = {JAMA neurology},
year = {2013},
doi = {10.1001/jamaneurol.2013.1925},
pmid = {23588557},
url = {https://doi.org/10.1001/jamaneurol.2013.1925}
}
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