Home › Research › Biomarkers
Plasma NfL and cognitive functioning in older adults: The moderating role of HDL cholesterol
Ramkrishna K Singh, Semere Bekena, Yiqi Zhu, Carlos Cruchaga, Steven E Arnold, Beau M Ances, Ganesh M Babulal. Alzheimer's & dementia (Amsterdam, Netherlands), 2025-10-14
Topic: Brain imaging, connectivity and assessment
Significant interaction effects were observed: MoCA (β = -1.86×10-4, P = 0.006) and PACC (β = -4.0×10-5, P = 0.004), indicating HDL moderates the negative association between NfL and cognition. These findings suggest that HDL modifies the cognitive impact of neurodegeneration, highlighting the importance of metabolic-neurological interactions. HIGHLIGHTS: High-density lipoprotein (HDL) cholesterol moderates the negative association between plasma neurofilament light chain (NfL) and cognition.Higher HDL levels intensify the negative effect of NfL on cognitive performance.Findings challenge the assumption of HDL's uniformly protective role.Results support the integrated use of metabolic and neurodegenerative biomarkers.
Key findings
- Significant interaction effects were observed: MoCA (β = -1.86×10-4, P = 0.006) and PACC (β = -4.0×10-5, P = 0.004), indicating HDL moderates the negative association between NfL and cognition.
- These findings suggest that HDL modifies the cognitive impact of neurodegeneration, highlighting the importance of metabolic-neurological interactions.
- HIGHLIGHTS: High-density lipoprotein (HDL) cholesterol moderates the negative association between plasma neurofilament light chain (NfL) and cognition.Higher HDL levels intensify the negative effect of NfL on cognitive performance.Findings challenge the assumption of HDL's uniformly protective role.Results support the integrated use of metabolic and neurodegenerative biomarkers.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Participants417
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded 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, multi-centre collaboration and free to read, so those were left out: it earned 31 of the 56 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia (Amsterdam, Netherlands)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 417 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 | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41098318) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 31 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 31 of the 56 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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 7 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
Singh, R. K., Bekena, S., Zhu, Y., Cruchaga, C., Arnold, S. E., Ances, B. M., et al. (2025). Plasma NfL and cognitive functioning in older adults: The moderating role of HDL cholesterol. Alzheimer's & dementia (Amsterdam, Netherlands). https://doi.org/10.1002/dad2.70205
Vancouver
Singh RK, Bekena S, Zhu Y, Cruchaga C, Arnold SE, Ances BM, et al. Plasma NfL and cognitive functioning in older adults: The moderating role of HDL cholesterol. Alzheimer's & dementia (Amsterdam, Netherlands). 2025. doi:10.1002/dad2.70205. PMID: 41098318.
BibTeX
@article{singh2025-41098318,
author = {Singh, Ramkrishna K and Bekena, Semere and Zhu, Yiqi and Cruchaga, Carlos and Arnold, Steven E and Ances, Beau M and Babulal, Ganesh M},
title = {{Plasma NfL and cognitive functioning in older adults: The moderating role of HDL cholesterol}},
journal = {Alzheimer's \& dementia (Amsterdam, Netherlands)},
year = {2025},
doi = {10.1002/dad2.70205},
pmid = {41098318},
url = {https://doi.org/10.1002/dad2.70205}
}