Serum cholesterol changes after midlife and late-life cognition: twenty-one-year follow-up study
Solomon A, Kåreholt I, Ngandu T, Winblad B, Nissinen A, Tuomilehto J, Soininen H, Kivipelto M.. Neurology, 2007-03-01
Topic: Risk, prevention and care in population studies
Background Longitudinal studies have shown that high serum total cholesterol (TC) at midlife is a risk factor for dementia/Alzheimer disease. The significance of TC later in life is unclear. Objective To investigate changes in serum TC from midlife to late life and their relationship with late-life cognition. Methods Participants of the Cardiovascular Risk Factors, Aging and Dementia study were derived from random, population-based samples previously studied in a survey in 1972, 1977, 1982, or 1987. After an average follow-up of 21 years, 1,449 individuals aged 65 to 79 were reexamined in 1998. Results Serum TC levels decreased in most individuals. High midlife TC represented a risk factor for more severe cognitive impairment later in life, and the values were significantly different between the control, mild cognitive impairment, and dementia groups. There were no significant differences in serum TC at reexamination. A moderate decrease in serum TC from midlife to late life (0.5 to 2 mmol/L) was significantly associated with the risk of a more impaired late-life cognitive status, even after adjusting for age, follow-up time, sex, years of formal education, midlife cholesterol, changes in body mass index, APOE epsilon4 genotype, history of myocardial infarction/stroke/diabetes, and lipid-lowering treatment. Conclusions The relationship between serum total cholesterol (TC) and dementia seems to be bidirectional. High midlife serum TC is a risk factor for subsequent dementia/Alzheimer disease, but decreasing serum TC after midlife may reflect ongoing disease processes and may represent a risk marker for late-life cognitive impairment.
Key findings
- Background Longitudinal studies have shown that high serum total cholesterol (TC) at midlife is a risk factor for dementia/Alzheimer disease.
- Results Serum TC levels decreased in most individuals.
- High midlife TC represented a risk factor for more severe cognitive impairment later in life, and the values were significantly different between the control, mild cognitive impairment, and dementia groups.
- There were no significant differences in serum TC at reexamination.
- A moderate decrease in serum TC from midlife to late life (0.5 to 2 mmol/L) was significantly associated with the risk of a more impaired late-life cognitive status, even after adjusting for age, follow-up time, sex, years of formal education, midlife cholesterol, changes in body mass index, APOE epsilon4 genotype, history of myocardial infarction/stroke/diabetes, and lipid-lowering treatment.
Why it matters
This 21-year follow-up study found that high cholesterol at midlife was a risk factor for worse late-life cognition, and that a moderate decrease in cholesterol from midlife to late life was linked to more impaired cognition. It describes associations over time but does not test whether changing cholesterol affects Alzheimer disease.
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Study details
- Study designlongitudinal study
- Participants1,449
- Evidence strengthModerate
How this study scored 66/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and 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 longitudinal study following the same 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 | 1 / 5 | 2007 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,449 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 | 6 / 7 | Cited 310 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.8 citations a year over 21 year(s) since 2007 |
| Impact for its field and year | 4 / 6 | Cited 13.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 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 Miia Kivipelto: h-index 107 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Karolinska Institutet: institution h-index 1,477 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17339582) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 66 / 100 | — |
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Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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 8 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
Solomon, A., Kåreholt, I., Ngandu, T., Winblad, B., Nissinen, A., Tuomilehto, J., et al. (2007). Serum cholesterol changes after midlife and late-life cognition: twenty-one-year follow-up study. Neurology. https://doi.org/10.1212/01.wnl.0000256368.57375.b7
Vancouver
Solomon A, Kåreholt I, Ngandu T, Winblad B, Nissinen A, Tuomilehto J, et al. Serum cholesterol changes after midlife and late-life cognition: twenty-one-year follow-up study. Neurology. 2007. doi:10.1212/01.wnl.0000256368.57375.b7. PMID: 17339582.
BibTeX
@article{solomon2007-17339582,
author = {Solomon, A. and Kåreholt, I. and Ngandu, T. and Winblad, B. and Nissinen, A. and Tuomilehto, J. and Soininen, H. and Kivipelto, M.},
title = {{Serum cholesterol changes after midlife and late-life cognition: twenty-one-year follow-up study}},
journal = {Neurology},
year = {2007},
doi = {10.1212/01.wnl.0000256368.57375.b7},
pmid = {17339582},
url = {https://doi.org/10.1212/01.wnl.0000256368.57375.b7}
}
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