Blood pressure variability and plasma Alzheimer’s disease biomarkers in older adults

Abstract

Blood pressure variability is an emerging risk factor for Alzheimer’s disease in older adults, independent of average blood pressure levels. Growing evidence suggests increased blood pressure variability is linked to Alzheimer’s disease pathophysiology indexed by cerebrospinal fluid and positron emission tomography markers, but relationships with plasma Alzheimer’s disease markers have not been investigated. In this cross-sectional study of 54 community-dwelling older adults (aged 55–88, mean age 69.9 [8.2 SD]), elevated blood pressure variability over 5 min was associated with lower levels of plasma Aβ1–42 (standardized ß = − 0.36 [95% CI − 0.61, − 0.12]; p = 0.005; adjusted R2 = 0.28) and Aβ1–42: Aβ1–40 ratio (ß = − 0.49 [95% CI − 0.71, − 0.22]; p < 0.001; adjusted R2 = 0.28), and higher levels of total tau (ß = 0.27 [95% CI 0.01, 0.54]; p = 0.04; adjusted R2 = 0.19) and Ptau181:Aβ1–42 ratio (ß = 0.26 [95% CI 0.02, 0.51]; p = 0.04; adjusted R2 = 0.22). Findings suggest higher blood pressure variability is linked to plasma biomarkers of increased Alzheimer’s disease pathophysiology.

Long‐term blood pressure patterns in midlife and dementia in later life: Findings from the Framingham Heart Study

“…We defined BPV using SD of five visits spanning up to 22 years of midlife, and while this reflects variability over a longer observation period, previous studies have used data from shorter measure‐to‐measure intervals (e.g., 2 years). While our Offspring cohort was followed‐up every 4 years and shorter intervals could not be obtained with these data, we believe that shorter intervals and more visits may reveal a stronger association between BPV and dementia, as it did for findings from the Alzheimer's Disease Neuroimaging Initiative, which used three to four BP measurements over the course of 12 months 16,72 …”

“…A single or an average measure of BP does not accurately capture long‐term BP patterns due to their fluctuating nature 9–12 but they have been widely used to represent BP due to difficulties associated with longitudinal examination of BP. Measures that better take into account an individual's long‐term BP patterns have been attracting attention in investigating the effect of BP on various clinical and functional outcomes 13–16 …”

“…Fine grained (beat‐to‐beat or frequently sampled, e.g., every 10 minutes) long‐term BP or ambulatory BP recordings offer a new richness of data but long‐term impact will take time to ascertain. Though sparsely sampled, what is currently available is visit‐to‐visit BP variability (BPV), which has gained attention as a better integration of the total load of hemodynamic risk markers, compared to single BP measurements 16–18 . Both short‐term and long‐term variability have been associated with important prognostic implications, including cardiovascular health, mortality, depression, and cognitive disorders 11,16,19–21 .…”

“…Both short‐term and long‐term variability have been associated with important prognostic implications, including cardiovascular health, mortality, depression, and cognitive disorders 11,16,19–21 . It is postulated that higher BPV could lead to cognitive dysfunction 17,22,23 and the development of Alzheimer's disease (AD) 16,24,25 by contributing to arterial stiffness and altering cerebral blood flow 22,26,27 …”

“…Measures that better take into account an individual's long-term BP patterns have been attracting attention in investigating the effect of BP on various clinical and functional outcomes. [13][14][15][16] Fine grained (beat-to-beat or frequently sampled, e.g., every 10 minutes) long-term BP or ambulatory BP recordings offer a new richness of data but long-term impact will take time to ascertain.…”