Key result
Genetically lower BP links to reduced vascular brain injury but not Alzheimer's disease pathology.
Why the study?
It was uncertain whether the dementia-reduction benefit of lower blood pressure stems solely from mitigating vascular brain injury or also extends to directly influencing Alzheimer disease pathology.
Does genetically proxied lower blood pressure reduce neuropathological measures of vascular brain injury and Alzheimer's disease pathology?
Observational (n=7,786)
Does genetically proxied lower blood pressure reduce neuropathological measures of vascular brain injury and Alzheimer's disease pathology?
Genetically proxied lower blood pressure protects against dementia by mitigating vascular brain injury rather than directly affecting Alzheimer's disease pathology.
Supports BP lowering for vascular brain protection in dementia; leaves open direct AD effects and requires trial confirmation.
INTRODUCTION: Lower blood pressure (BP) is linked to reduced dementia risk, though it is uncertain whether this benefit stems solely from mitigating vascular brain injury (VBI) or also extends to directly influencing Alzheimer's disease (AD) pathology. We leveraged Mendelian randomization (MR) to assess whether lifelong lower BP is causally associated with neuropathological correlates of VBI and AD. METHODS: We identified genetic proxies for systolic and diastolic BP (n = 1,028,980) and applied them in MR analyses of post mortem neuropathological measures of VBI and AD (n = 6363-7786). RESULTS: Genetically proxied lower systolic BP associated with reduced risk of all VBI measures, including atherosclerosis, arteriolosclerosis, gross infarcts, and microinfarcts. There was no evidence for associations between systolic BP and AD pathology, including measures of amyloid and tau pathology. Diastolic BP analyses yielded similar results. DISCUSSION: These findings suggest that BP-lowering protects against dementia by mitigating VBI rather than by directly affecting AD pathology. HIGHLIGHTS: It is uncertain whether blood pressure impacts dementia risk solely through its effects on blood vessel health, or whether it also impacts Alzheimer's disease (AD) pathology. We performed a Mendelian randomization study using genetic predictors of blood pressure applied to a unique autopsy study of neuropathological correlates of both vascular brain injury and AD pathology. We found evidence that genetically lowered blood pressure solely impacts vascular brain injury, with no effects on AD pathology.
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Daghlas et al. (2025) conducted an observational in Vascular brain injury and Alzheimer's disease (n=7,786). Genetically proxied lower blood pressure was evaluated on Neuropathological measures of vascular brain injury and Alzheimer's disease. Genetically proxied lower blood pressure was associated with reduced risk of vascular brain injury measures (n=6363-7786), but showed no association with Alzheimer's disease pathology.
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