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Updated: Sep 11, 2025

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Lipoprotein(a) and risk of dementia: findings from three cohort studies

Peter E Thomas1,2,3, Signe Vedel-Krogh1,2,3, Sune F Nielsen1,2

  • 1Department of Clinical Biochemistry, Copenhagen University Hospital-Herlev and Gentofte, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark.

European Heart Journal
|August 18, 2025
PubMed

Insights

High lipoprotein(a) levels may increase vascular dementia risk, but not Alzheimer's disease risk. Further research is needed to confirm the link between lipoprotein(a) and dementia.

Area of Science:

  • Cardiovascular Science
  • Neurology
  • Genetics

Background:

  • Dementia and atherosclerotic cardiovascular disease (ASCVD) share risk factors.
  • High lipoprotein(a) is a known ASCVD risk factor, but its role in dementia is unclear.

Purpose of the Study:

  • To investigate the association between lipoprotein(a) levels and the risk of Alzheimer's disease (AD) and vascular-related dementia (VaD).
  • To evaluate the impact of lipoprotein(a) lowering therapies in clinical trials.

Main Methods:

  • Analysis of lipoprotein(a) levels in 539,478 individuals from three large cohorts (Copenhagen General Population Study, Copenhagen City Heart Study, UK Biobank).
  • Longitudinal follow-up for up to 30.2 years to record AD and VaD diagnoses.
  • Statistical analysis accounting for the competing risk of death.

Main Results:

  • Lipoprotein(a) levels were not associated with AD or VaD risk on continuous scales.
  • In UK Biobank, higher lipoprotein(a) levels correlated with increased VaD risk (P = .01) when accounting for competing risks.
  • In Copenhagen studies, LPA KIV-2 repeats (indicating smaller isoform size) were associated with increased AD risk (SHR 1.25).

Conclusions:

  • Low lipoprotein(a) levels are not linked to increased dementia risk.
  • Very high lipoprotein(a) levels or small isoform size may potentially increase dementia risk, warranting further investigation.
Abstract

Keywords:
Alzheimer’s diseaseDementiaLipoprotein(a)Risk factorsVascular-related dementia

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