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78/100

✓ Peer-reviewed alzhub usefulness score 78 out of 100. Drug development

Topic: Amyloid, tau and blood-test diagnosis

Plain-language summary

Objective To examine whether genetic variation affecting the expression or function of lipid-lowering drug targets is associated with Alzheimer disease (AD) risk, to evaluate the potential impact of long-term exposure to corresponding therapeutics. Methods We conducted Mendelian randomization analyses using variants in genes that encode the protein targets of several approved lipid-lowering drug classes: HMGCR (encoding the target for statins), PCSK9 (encoding the target for PCSK9 inhibitors, eg, evolocumab and alirocumab), NPC1L1 (encoding the target for ezetimibe), and APOB (encoding the target of mipomersen). Variants were weighted by associations with low-density lipoprotein cholesterol (LDL-C) using data from lipid genetics consortia (n up to 295,826). We meta-analyzed Mendelian randomization estimates for regional variants weighted by LDL-C on AD risk from 2 large samples (total n = 24,718 cases, 56,685 controls). Results Models for HMGCR, APOB, and NPC1L1 did not suggest that the use of related lipid-lowering drug classes would affect AD risk. In contrast, genetically instrumented exposure to PCSK9 inhibitors was predicted to increase AD risk in both of the AD samples (combined odds ratio per standard deviation lower LDL-C inducible by the drug target = 1.45, 95% confidence interval = 1.23-1.69). This risk increase was opposite to, although more modest than, the degree of protection from coronary artery disease predicted by these same methods for PCSK9 inhibition. Interpretation We did not identify genetic support for the repurposing of statins, ezetimibe, or mipomersen for AD prevention. Notwithstanding caveats to this genetic evidence, pharmacovigilance for AD risk among users of PCSK9 inhibitors may be warranted. ANN NEUROL 2020;87:30-39.

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APA 7th

Williams, D. M., Finan, C., Schmidt, A. F., Burgess, S., & Hingorani, A. D. (2020). Lipid lowering and Alzheimer disease risk: A mendelian randomization study. Annals of neurology. https://doi.org/10.1002/ana.25642

Vancouver

Williams DM, Finan C, Schmidt AF, Burgess S, Hingorani AD. Lipid lowering and Alzheimer disease risk: A mendelian randomization study. Annals of neurology. 2020. doi:10.1002/ana.25642. PMID: 31714636.

BibTeX

@article{williams2020-31714636,
  author  = {Williams, D. M. and Finan, C. and Schmidt, A. F. and Burgess, S. and Hingorani, A. D.},
  title   = {{Lipid lowering and Alzheimer disease risk: A mendelian randomization study}},
  journal = {Annals of neurology},
  year    = {2020},
  doi     = {10.1002/ana.25642},
  pmid    = {31714636},
  url     = {https://doi.org/10.1002/ana.25642}
}

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How to read this study

Design: this is a pooled review. It combines earlier studies, so it is only as good as the studies it pools. Check how many were included, whether they were similar enough to combine, and whether the authors report inconsistency between them.
Size: the record lists 24,718 participants. Ask whether that is enough for the question, and who they were.
Effect: the record gives no effect size, so the summary above cannot say how large any difference was.

What the evidence grade means here

This page is graded low. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Low means the abstract matched neither pattern. It is the default label, and it does not mean the work is poor; many sound lab and imaging papers land here. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

Objective To examine whether genetic variation affecting the expression or function of lipid-lowering drug targets is associated with Alzheimer disease (AD) risk, to evaluate the potential impact of long-term exposure to corresponding therapeutics.
Results Models for HMGCR, APOB, and NPC1L1 did not suggest that the use of related lipid-lowering drug classes would affect AD risk.

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Study details

Participants24,718
Evidence strengthLow

How this study scored 78/100

Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 45 of the 58 points we could judge it on, which is 78 out of 100.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (Annals of neurology)
Journal's citation record	— / 4	No journal record from OpenAlex — left out of this score
Study design	12 / 12	A meta-analysis pooling many studies (from PubMed type “Meta-Analysis”)
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	2 / 5	2020 — within 10 year(s) of the newest study here
Sample size	4 / 4	24,718 participants
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	3 / 3	Studied in people (participant count stated)
Randomized / blinded	0 / 2	A review of other studies — randomization is not credited here
Times cited	— / 7	No citation count (not found in OpenAlex) — left out of this score
Citations per year	— / 5	No citation count or no year — left out of this score
Impact for its field and year	— / 6	No field-weighted citation impact (OpenAlex has none yet) — left out of this score
Cited by studies here	— / 6	Not yet checked against this library's citation graph — left out of this score
Still being cited	— / 4	No yearly citation counts — left out of this score
Senior author's track record	— / 4	Senior author's record not available — left out of this score
Institution's track record	— / 3	No institution listed in OpenAlex — left out of this score
Multicenter collaboration	— / 3	Institutions not listed — left out of this score
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 31714636)
Free to read	2 / 2	Free to read
Points	45 / 58	Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 45 of the 58 points we could judge it on is 78 out of 100.
Total	78 / 100	—

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