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Cited by 82Dementia and Cognitive Impairment ResearchLipoproteins and Cardiovascular HealthAlzheimer's disease research and treatments

The relationship between midlife dyslipidemia and lifetime incidence of dementia: A systematic review and meta‐analysis of cohort studies

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Wee, Jason, Sukudom, Sara, Bhat, Saiuj, Marklund, Matti, Peiris, Niridu Jude, Hoyos, Camilla M, Patel, Sanjay, Naismith, Sharon L +2 more·2023·Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
DOI 10.1002/dad2.12395PMC PMC9993469
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Abstract

Introduction: We conducted a systematic review and meta‐analysis to review the relationship between midlife dyslipidemia and lifetime incident dementia. Methods: The databases Medline, Embase, Scopus, Web of Science, and Cochrane were searched from inception to February 20, 2022. Longitudinal studies examining the relationship between midlife lipid levels on dementia, dementia subtypes, and/or cognitive impairment were pooled using inverse‐variance weighted random‐effects meta‐analysis. Results: Seventeen studies (1.2 million participants) were included. Midlife hypercholesterolemia was associated with increased incidence of mild cognitive impairment (effect size [ES] = 2.01; 95% confidence interval [CI] 1.19 to 2.84; I 2 = 0.0%) and all‐cause dementia (ES = 1.14; 95% CI: 1.07 to 1.21; I 2 = 0.0%). Each 1 mmol/L increase in low‐density lipoprotein was associated with an 8% increase (ES = 1.08, 95% CI: 1.03 to 1.14; I 2 = 0.3%) in incidence of all‐cause dementia. Discussion: Midlife dyslipidemia is associated with an increased risk of cognitive impairment in later life.

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  • In adults aged <65 years, each 1 mmol/L increase in LDL-C is associated with an 8% increased incidence of all-cause dementia (HR 1.08, 95% CI 1.03-1.14).

    “A newer meta-analysis of LDL-C in adults aged &lt;65 years followed up for &gt; 12 months, found 3 cohort studies with 1,138,488 participants, all from UK, and reported each 1mmol/l increase in LDL-C was associated with 8% increased incidence of all cause dementia (1.08; 1.03 - 1.14; I 2 = 0.3%). (153)”

    From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [153]

    The Results section, “Association between midlife dyslipidemia and all-cause dementia” (page unavailable), reports an 8% increase in incident dementia per 1 mmol/L rise in LDL (ES 1.08, 95% CI 1.03–1.14; I² = 0.3%). The Methods eligibility criteria specify adults under 65 at lipid sampling and at least 12 months of follow-up. However, Table 1 lists the relevant UK data as three cohorts totaling 1,138,488 participants from two named studies, Gong and Iwagami, rather than three distinct studies. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Excess brain cholesterol is associated with increased stroke risk and higher deposition of brain amyloid and tau.

    “Excess brain cholesterol is associated with increased stroke risk and higher deposition of brain amyloid and tau. (153)”

    From Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission (2024) · cites this paper as [153]

    The Introduction (page not provided) proposes that a metabolite of systemic cholesterol may cross the blood–brain barrier and promote amyloid-beta and tau deposition. It does not establish an association involving excess brain cholesterol or report increased stroke risk; its vascular discussion concerns carotid atherosclerosis and vascular dementia. (LLM, conf=0.86)

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Authors
Wee, J., Sukudom, S., Bhat, S., Marklund, M., Peiris, N. J., Hoyos, C. M., Patel, S., Naismith, S. L., Dwivedi, G., & Misra, A.
Affiliations
  • Fiona Stanley Hospital (AU)
  • The University of Sydney (AU)
  • Royal Perth Hospital (AU)
  • Uppsala University (SE)
  • The Heart Research Institute (AU)
  • The University of Western Australia (AU)
Corresponding author
Misra, Ashish
ORCID
Venue
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Publisher
Wiley
Published
2023-01
Volume
15
Issue
1
Pages
e12395-e12395
ISSN
2352-8729 (ISSN-L)
DOI
10.1002/dad2.12395
PMC
PMC9993469
OpenAlex
W4323645482
Cited by
82
References
13
Citations by year
2026: 17 · 2025: 34 · 2024: 26 · 2023: 5
FWCI
3.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UWA Profiles and Research Repository (UWA) (submittedVersion, cc-by-nc-nd)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
hypercholesterolemia, dementia incidence, mild cognitive impairment, low-density lipoprotein, serum lipids, cognitive impairment, Alzheimer's disease

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