Genetically proxied blood pressure, vascular brain injury, and Alzheimer's disease pathology

TL;DR

This study finds that lower blood pressure reduces dementia risk by protecting blood vessels in the brain, but does not directly affect Alzheimer's disease pathology.

Contribution

The study uses genetic data to clarify that lower blood pressure reduces vascular brain injury but does not influence Alzheimer's pathology.

Findings

Genetically lower systolic blood pressure is linked to reduced vascular brain injury measures like atherosclerosis and infarcts.

No evidence was found linking systolic blood pressure to Alzheimer's disease pathology markers like amyloid or tau.

Diastolic blood pressure showed similar results to systolic blood pressure in relation to vascular brain injury.

Abstract

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.

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).

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.

These findings suggest that BP‐lowering protects against dementia by mitigating VBI rather than by directly affecting AD pathology.

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.

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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