# Association Between Short‐Term Blood Pressure Variability and the Alzheimer's Disease Continuum

## TL;DR

Short-term blood pressure variability is linked to cognitive decline and brain changes in Alzheimer's disease, suggesting a vascular pathway and potential treatment target.

## Contribution

This study identifies short-term blood pressure variability as a potential modifiable risk factor for Alzheimer's disease through its association with brain structure and cognitive symptoms.

## Key findings

- Nightly diastolic blood pressure variability correlates with higher neuropsychiatric inventory scores.
- Increased systolic blood pressure variability is linked to anxiety and tau levels in Alzheimer's patients.
- Brain regions like the left cuneus and right medial orbitofrontal cortex mediate the relationship between blood pressure variability and symptoms.

## Abstract

Emerging evidence indicates that blood pressure variability (BPV) is a modifiable vascular risk factor for Alzheimer's disease (AD). Herein, we aimed to systematically evaluate the potential role of short‐term BPV across the AD continuum.

This study included 263 patients on the AD continuum from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2023, and December 31, 2023. 24‐h ambulatory blood pressure monitoring was performed to obtain blood pressure measurements and evaluate BPV. Partial Spearman's correlation and restricted cubic spline analysis were performed to assess the associations between BPV and neuropsychological tests, cerebrospinal fluid biomarkers, and multimodal neuroimaging measures, respectively. The mediating effects of multimodal neuroimaging measures on the association between BPV and neuropsychiatric symptoms (NPS) were analyzed.

The elevated standard deviation (SD) and average real variability of nightly diastolic blood pressure (DBP) were correlated with higher Neuropsychiatric Inventory (NPI) scores (r = 0.19, p = 0.034; r = 0.22, p = 0.013). The increased SD of nightly systolic blood pressure (SBP) was correlated with increased Hamilton Anxiety Scale (HAMA) scores and total tau levels (r = 0.20, p = 0.026; r = 0.17, p = 0.027), and elevated coefficient of variation (CV) of nightly SBP was correlated with higher HAMA scores and lower Aβ42/40 levels (r = 0.20, p = 0.026; r = –0.18, p = 0.021). The nightly variability of SBP showed an inverted U‐shaped relationship with Montreal Cognitive Assessment scores (P for nonlinear = 0.008; P for nonlinear = 0.015; P for nonlinear = 0.021). The left cuneus volume mediated 29.41% of the association between the CV of nightly SBP and HAMA scores, while the right medial orbitofrontal thickness mediated 35.44% of the association between the CV of nightly DBP and NPI scores.

This study suggests that short‐term BPV may play a role in the AD continuum. These findings provide evidence of a vascular pathway to AD, as well as a potential and accessible intervention target for patients on the AD continuum.

Short‐Term blood pressure variability (BPV), particularly nightly BPV, is associated with cognition, neuropsychiatric symptoms (NPS), multiple cerebrospinal fluid biomarkers, and multimodal neuroimaging measures across the Alzheimer's disease (AD) continuum. The correlation between BPV and NPS was partly mediated by the left cuneus volume and right medial orbitofrontal thickness.