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61/100

✓ Peer-reviewed alzhub usefulness score 61 out of 100. Genetics

Topic: Brain proteins, microglia and lab models

Plain-language summary

Objective To interrogate a poly-T variant (rs10524523, '523) in TOMM40 , a gene adjacent to the APOE gene on chromosome 19, in older persons with APOE ε3/3 homozygosity for association with cognitive decline, the clinical hallmark of Alzheimer disease (AD). Methods Data came from participants in 2 cohort studies of aging and dementia who underwent annual clinical evaluations for up to 21 years. APOE and TOMM40 '523 genotypes were determined from DNA from blood or brain samples. Linear mixed models compared the rates of decline in cognition among APOE ε3/3 carriers with different '523 genotypes. Results The 1,170 APOE ε3/3 homozygotes were of European ancestry, were free of dementia at baseline, and had an average age of 78.5 years at baseline. Three major genotypes at the '523 variant were linked to APOE ε3/3; 26.5% had 2 short poly-Ts (S/S), 48.5% had 1 short and 1 very long poly-T (S/VL), and 24.0% had 2 very long poly-Ts (VL/VL). Participants with '523-S/S had faster decline in global cognition than participants with '523-S/VL or VL/VL ( p = 0.002). The same association was observed for episodic memory ( p p = 0.003) but not for working memory, perceptual speed, or visuospatial ability. Conclusions Our data reveal an association of APOE ε3/3- TOMM40 '523 haplotypes with cognitive decline in community-based older persons such that the S/S poly-T genotype is related to faster cognitive decline, primarily in the domains of episodic and semantic memory.

What this study adds

Evidence grade: Moderate

This is a follow-up (cohort) study. Among older people with the APOE ε3/3 genotype, a particular TOMM40 variant was associated with faster decline in global cognition and episodic memory. Reported effect size: 26.5%; 48.5%; 24.0%.

Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Yu, L., Lutz, M. W., Wilson, R. S., Burns, D. K., Roses, A. D., Saunders, A. M., et al. (2017). TOMM40'523 variant and cognitive decline in older persons with APOE ε3/3 genotype. Neurology. https://doi.org/10.1212/wnl.0000000000003614

Vancouver

Yu L, Lutz MW, Wilson RS, Burns DK, Roses AD, Saunders AM, et al. TOMM40'523 variant and cognitive decline in older persons with APOE ε3/3 genotype. Neurology. 2017. doi:10.1212/wnl.0000000000003614. PMID: 28108637.

BibTeX

@article{yu2017-28108637,
  author  = {Yu, L. and Lutz, M. W. and Wilson, R. S. and Burns, D. K. and Roses, A. D. and Saunders, A. M. and Gaiteri, C. and De Jager, P. L. and others},
  title   = {{TOMM40'523 variant and cognitive decline in older persons with APOE ε3/3 genotype}},
  journal = {Neurology},
  year    = {2017},
  doi     = {10.1212/wnl.0000000000003614},
  pmid    = {28108637},
  url     = {https://doi.org/10.1212/wnl.0000000000003614}
}

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How to read this study

Design: this is a follow-up (cohort) study. People are observed over time and not assigned to anything, so an association can reflect other differences between groups. Look at how long follow-up lasted, how many dropped out, and whether the authors adjusted for age, education and other health conditions.
Size: the record gives no participant count. Look for one in the original before trusting a pattern.
Effect: the record reports “26.5%; 48.5%; 24.0%”. A statistically significant result can still be small in daily life.

What the evidence grade means here

This page is graded moderate. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Moderate means the abstract mentions a cohort, case-control or longitudinal design. 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

Results The 1,170 APOE ε3/3 homozygotes were of European ancestry, were free of dementia at baseline, and had an average age of 78.5 years at baseline.

Why it matters

Among older people with the APOE ε3/3 genotype, a particular TOMM40 variant was associated with faster decline in global cognition and episodic memory. This is an observational finding about genetic risk and does not show any treatment or prevention.

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Study details

Study designcohort study
Effect size26.5%; 48.5%; 24.0%
Evidence strengthModerate

How this study scored 61/100

Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for sample size, studied in people and randomized / blinded because the record does not state it.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (Neurology)
Journal's citation record	4 / 4	Neurology: journal h-index 525 (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	2 / 5	2017 — within 10 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	2 / 3	Effect reported as a number, without an interval or test
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	4 / 7	Cited 77 times (OpenAlex, 2026-10-10)
Citations per year	2 / 5	7.0 citations a year over 11 year(s) since 2017
Impact for its field and year	3 / 6	Cited 4.4× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	2 / 6	Cited by 5 other studies in this library
Still being cited	2 / 4	Cited 32 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	4 / 4	Last-listed author David Alan Bennett: h-index 197 (OpenAlex, whole career)
Institution's track record	3 / 3	Harvard University: institution h-index 3,235 (OpenAlex)
Multicenter collaboration	2 / 3	OpenAlex lists 6 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 28108637)
Free to read	0 / 2	Behind a paywall — scores zero
Total	61 / 100	—

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