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62/100

✓ Peer-reviewed alzhub usefulness score 62 out of 100. Treatments

Topic: Brain proteins, microglia and lab models

Background Alzheimer disease (AD) prevention is a public health priority, yet the impact of dietary carotenoids on cognitive decline, particularly in apolipoprotein E (APOE) ε4 carriers, remains unclear. Objectives The objective of this study was to examine whether the APOE ε4 genotype modifies the relationship between blood carotenoid concentrations and global cognition. Methods This study was conducted within the Mediterranean-Dietary Approaches to Stop Hypertension intervention for neurodegenerative delay trial, a 3-y randomized controlled trial comparing the effects of the Mediterranean-Dietary Approaches to Stop Hypertension intervention for neurodegenerative delay diet with the usual diet on global cognition in older adults. Eligible participants were ≥65 y, had a body mass index (in kg/m 2 ) >25, a family history of AD, suboptimal diets, and a Montreal cognitive assessment score ≥22. The primary outcome was 3-y change in global cognitive function, assessed using a validated composite cognitive score converted to standardized units (SUs). Baseline plasma carotenoid concentrations were measured in a subgroup of participants (n = 442). Mixed-effects models were used to test the interaction between APOE ε4 status and baseline carotenoid concentrations on cognitive trajectories. Results The mean age was 70.0 y for noncarriers (n = 308) and 69.4 y for APOE ε4 carriers (n = 134). Among APOE ε4 carriers, a 1-unit increment in plasma total carotenoids at baseline was associated with higher global cognitive scores [β = 0.17 SU; 95% confidence interval (CI): 0.06, 0.28 SU; P = 0.009]. Similar associations were observed for β-carotene (β = 0.13 SU; 95% CI: 0.05, 0.21 SU; P = 0.001), α-carotene (β = 0.09 SU; 95% CI: 0.02, 0.15 SU; P = 0.008), lutein plus zeaxanthin (β = 0.14 SU; 95% CI: 0.04, 0.25 SU; P = 0.008), lycopene (β = 0.17 SU; 95% CI: 0.07, 0.28 SU; P = 0.005), and β-cryptoxanthin (β = 0.13 SU; 95% CI: 0.05, 0.21 SU; P = 0.03). Associations in noncarriers were weaker or nonsignificant. Conclusions Higher plasma carotenoid concentrations were associated with slower cognitive decline in APOE ε4 carriers, potentially mitigating genetic risk. This trial was registered at clinicaltrials.gov as NCT02817074.

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APA 7th

Liu, X., Sacks, F. M., Beck, T., Tangney, C. C., Willett, W. C., Yassine, H., et al. (2025). Apolipoprotein E ε4-dependent associations between carotenoids and cognitive decline: Findings from the MIND (Mediterranean-DASH Intervention for Neurodegenerative delay) randomized controlled trial. The American journal of clinical nutrition. https://doi.org/10.1016/j.ajcnut.2025.08.012

Vancouver

Liu X, Sacks FM, Beck T, Tangney CC, Willett WC, Yassine H, et al. Apolipoprotein E ε4-dependent associations between carotenoids and cognitive decline: Findings from the MIND (Mediterranean-DASH Intervention for Neurodegenerative delay) randomized controlled trial. The American journal of clinical nutrition. 2025. doi:10.1016/j.ajcnut.2025.08.012. PMID: 40876538.

BibTeX

@article{liu2025-40876538,
  author  = {Liu, X. and Sacks, F. M. and Beck, T. and Tangney, C. C. and Willett, W. C. and Yassine, H. and Dhana, K. and Aggarwal, N. T. and others},
  title   = {{Apolipoprotein E ε4-dependent associations between carotenoids and cognitive decline: Findings from the MIND (Mediterranean-DASH Intervention for Neurodegenerative delay) randomized controlled trial}},
  journal = {The American journal of clinical nutrition},
  year    = {2025},
  doi     = {10.1016/j.ajcnut.2025.08.012},
  pmid    = {40876538},
  url     = {https://doi.org/10.1016/j.ajcnut.2025.08.012}
}

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Key findings

Results The mean age was 70.0 y for noncarriers (n = 308) and 69.4 y for APOE ε4 carriers (n = 134).
Among APOE ε4 carriers, a 1-unit increment in plasma total carotenoids at baseline was associated with higher global cognitive scores [β = 0.17 SU; 95% confidence interval (CI): 0.06, 0.28 SU; P = 0.009].
Conclusions Higher plasma carotenoid concentrations were associated with slower cognitive decline in APOE ε4 carriers, potentially mitigating genetic risk.

Why it matters

In this trial, higher blood carotenoid levels at the start were linked to slower cognitive decline only in people who carry the APOE ε4 gene, not in non-carriers. This suggests that diet-related factors might help offset genetic risk, but the finding comes from a subgroup of 442 participants and needs confirmation.

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Study details

Study designrandomized controlled trial
Participants442
Evidence strengthHigh

How this study scored 62/100

Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (The American journal of clinical nutrition)
Journal's citation record	3 / 4	American Journal of Clinical Nutrition: journal h-index 499 (OpenAlex, 2026-10-29)
Study design	11 / 12	A randomised controlled trial
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	4 / 5	2025 — within 3 year(s) of the newest study here
Sample size	2 / 4	442 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)
Randomised / blinded	1 / 2	Randomised (as stated in the record)
Times cited	1 / 7	Cited 3 times (OpenAlex, 2026-10-10)
Citations per year	1 / 5	1.0 citations a year over 3 year(s) since 2025
Impact for its field and year	2 / 6	Cited 1.9× 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 3 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	3 / 4	Last-listed author Lisa Laverne Barnes: h-index 95 (OpenAlex, whole career)
Institution's track record	3 / 3	Harvard University: institution h-index 3,235 (OpenAlex)
Multi-centre collaboration	1 / 3	OpenAlex lists 3 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 40876538)
Free to read	2 / 2	Free to read
Total	62 / 100	—

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