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<p>Vascular dementia (VaD) is a devastating cerebrovascular disease with no disease-modifying treatments. Repurposing drugs for known risk factors could have clinical impact. Using Mendelian randomization, we proxied 46 lipid-lowering, antihypertensive and anti-inflammatory drug effects across five VaD outcomes: clinical diagnosis (<i>N</i> = 7,009 cases, <i>N</i> = 899,672 non-cases/controls) and neuroimaging features (max <i>N</i> = 50,559), white matter hyperintensity volume, fractional anisotropy, mean diffusivity and lacunar stroke diagnosis. Beta-1 adrenergic receptor indicated potential benefit (clinical diagnosis: odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.80–1.01; white matter hyperintensity volume: estimated causal effect = −0.03, 95% CI = −0.07–0.00; mean diffusivity: estimated causal effect = −0.18, 95% CI = −0.37–0.00; lacunar stroke: OR = 0.91, 95% CI = 0.80–1.03). Angiotensin-converting enzyme inhibition suggested increased VaD risk (OR = 1.12, 95% CI = 1.01–1.24). Findings remained largely null after multiple-testing correction. Here we show that although little evidence supported repurposing most lipid-lowering, antihypertensive and anti-inflammatory drugs for VaD prevention or treatment, beta-1 adrenergic receptor antagonism could be a promising repurposing candidate, but replication is needed as further data becomes available. Pharmacovigilance studies should examine angiotensin-converting enzyme inhibitors’ potential to increase risk.</p>

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Repurposing drugs for the prevention of vascular dementia using evidence from drug target Mendelian randomization

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月20日

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  • Victoria Taylor-Bateman,
  • Phazha Bothongo,
  • Venexia Walker,
  • Patrick G. Kehoe,
  • Liv Tybjærg Nordestgaard,
  • Yoav Ben-Shlomo,
  • Neil M. Davies,
  • Dylan M. Williams,
  • Emma L. Anderson

摘要

Vascular dementia (VaD) is a devastating cerebrovascular disease with no disease-modifying treatments. Repurposing drugs for known risk factors could have clinical impact. Using Mendelian randomization, we proxied 46 lipid-lowering, antihypertensive and anti-inflammatory drug effects across five VaD outcomes: clinical diagnosis (N = 7,009 cases, N = 899,672 non-cases/controls) and neuroimaging features (max N = 50,559), white matter hyperintensity volume, fractional anisotropy, mean diffusivity and lacunar stroke diagnosis. Beta-1 adrenergic receptor indicated potential benefit (clinical diagnosis: odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.80–1.01; white matter hyperintensity volume: estimated causal effect = −0.03, 95% CI = −0.07–0.00; mean diffusivity: estimated causal effect = −0.18, 95% CI = −0.37–0.00; lacunar stroke: OR = 0.91, 95% CI = 0.80–1.03). Angiotensin-converting enzyme inhibition suggested increased VaD risk (OR = 1.12, 95% CI = 1.01–1.24). Findings remained largely null after multiple-testing correction. Here we show that although little evidence supported repurposing most lipid-lowering, antihypertensive and anti-inflammatory drugs for VaD prevention or treatment, beta-1 adrenergic receptor antagonism could be a promising repurposing candidate, but replication is needed as further data becomes available. Pharmacovigilance studies should examine angiotensin-converting enzyme inhibitors’ potential to increase risk.