Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later
Nägga K, Gustavsson AM, Stomrud E, Lindqvist D, van Westen D, Blennow K, Zetterberg H, Melander O et al.. Neurology, 2017-12-01
Topic: Brain proteins, microglia and lab models
Objective To evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals. Methods This is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of β-amyloid (Aβ) and tau pathologies 20 years later (mean age 73 years) were detected by quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134), Aβ ( 18 F-flutemetamol) PET was also performed. Results CSF Aβ 42 and Aβ PET revealed Aβ pathology in approximately 20% of the cognitively healthy population and CSF Aβ 42 /phosphorylated tau (p-tau) ratio indicated both Aβ and tau pathology in 16%. Higher levels of triglycerides in midlife were independently associated with abnormal CSF Aβ 42 (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.03-1.75, p = 0.029) and abnormal Aβ 42 /p-tau ratio (OR 1.46, 95% CI 1.10-1.93; p = 0.009) adjusting for age, sex, APOE ε4, education, and multiple vascular risk factors. Triglycerides were also associated with abnormal Aβ PET in multivariable regression models, but the association was attenuated in the fully adjusted model. Increased levels of medium and large low-density lipoprotein subfractions were significantly associated with abnormal Aβ PET and large high-density lipoprotein particles were associated with decreased risk of abnormal Aβ PET. Conclusions Increased levels of triglycerides at midlife predict brain Aβ and tau pathology 20 years later in cognitively healthy individuals. Certain lipoprotein subfractions may also be risk factors for Aβ pathology. These findings further support an involvement of lipids in the very early stages of AD development.
Key findings
- Results CSF Aβ 42 and Aβ PET revealed Aβ pathology in approximately 20% of the cognitively healthy population and CSF Aβ 42 /phosphorylated tau (p-tau) ratio indicated both Aβ and tau pathology in 16%.
- Higher levels of triglycerides in midlife were independently associated with abnormal CSF Aβ 42 (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.03-1.75, p = 0.029) and abnormal Aβ 42 /p-tau ratio (OR 1.46, 95% CI 1.10-1.93; p = 0.009) adjusting for age, sex, APOE ε4, education, and multiple vascular risk factors.
- Triglycerides were also associated with abnormal Aβ PET in multivariable regression models, but the association was attenuated in the fully adjusted model.
- Increased levels of medium and large low-density lipoprotein subfractions were significantly associated with abnormal Aβ PET and large high-density lipoprotein particles were associated with decreased risk of abnormal Aβ PET.
- These findings further support an involvement of lipids in the very early stages of AD development.
Why it matters
In cognitively normal people, higher midlife triglycerides were linked to abnormal amyloid and tau biomarkers about 20 years later. This is an observational cohort finding, so it does not show that lowering triglycerides prevents Alzheimer disease.
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Study details
- Study designcohort study
- Participants134
- Effect sizeOR 1.46
- Evidence strengthModerate
How this study scored 70/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / 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 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 134 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 5 / 7 | Cited 112 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.2 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 3 / 6 | Cited 6.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 8 other studies in this library |
| Still being cited | 2 / 4 | Cited 36 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Oskar Hansson: h-index 148 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29196581) |
| Free to read | 2 / 2 | Free to read |
| Total | 70 / 100 | — |
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Read the original
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
Nägga, K., Gustavsson, A. M., Stomrud, E., Lindqvist, D., van Westen, D., Blennow, K., et al. (2018). Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later. Neurology. https://doi.org/10.1212/wnl.0000000000004749
Vancouver
Nägga K, Gustavsson AM, Stomrud E, Lindqvist D, van Westen D, Blennow K, et al. Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later. Neurology. 2018. doi:10.1212/wnl.0000000000004749. PMID: 29196581.
BibTeX
@article{nagga2018-29196581,
author = {Nägga, K. and Gustavsson, A. M. and Stomrud, E. and Lindqvist, D. and van Westen, D. and Blennow, K. and Zetterberg, H. and Melander, O. and others},
title = {{Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later}},
journal = {Neurology},
year = {2018},
doi = {10.1212/wnl.0000000000004749},
pmid = {29196581},
url = {https://doi.org/10.1212/wnl.0000000000004749}
}
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