Blood Pressure Variability May Lead to Neurodegeneration and Brain Shrinkage in Older Adults

Beat-to-beat blood pressure variability (BPV) has shown a direct correlation to nerve cell injury, brain shrinkage, and neurodegeneration in older adults.1

In a study conducted by the USC Leonard Davis School of Gerontology, Daniel Nation, PhD, professor of gerontology and medicine, USC Leonard Davis School, and colleagues found that dynamic instability – defined as moment-to-moment changes over a matter of minutes – is directly correlated with brain tissue loss in regions connected to memory and cognition.1

“Our findings show that even when average blood pressure is normal, instability from one heartbeat to the next may place stress on the brain,” Nation said in a statement. “These moment-to-moment swings appear to be associated with the same kinds of brain changes we see in early neurodegeneration.”1

Nation and colleagues investigated 105 adult patients between 55 and 89 years without major neurological or systemic diseases. Each participant was subject to brain magnetic resonance imaging and continuous blood pressure monitoring, quantifying beat-to-beat BPV through systolic average real variability (ARV) and pulse pressure variability using arterial stiffness index (ASI). Additionally, the team studied the effects of ARV and ASI on medial temporal lobe atrophy, plasma neurofilament light chain (NfL), and plasma glial fibrillary acidic protein (GFAP) via hierarchical linear regression.2

Ultimately, they found that the interaction between a higher ARV and ASI was significantly associated with left-sided medial temporal lobe atrophy in the designated region-of-interest (left hippocampus β = -252.79, P = .0002; right hippocampus β = -193.56, P = .001; left entorhinal cortex β = -0.13, P = .007), as well as false discovery rate-corrected voxel-based morphometry analysis (P = .03). This interactive effect was associated with increased plasma NfL (β = 3.88, P = .01), but not GFAP.2

These findings were also consistent across all subgroups, including age, sex, and average blood pressure. This implies that the fluctuations themselves may be a key risk factor, more so than overall pressure. Additionally, the brain changes were substantially more pronounced on the left side, which lines up with prior research and confirms the theory of the left hemisphere being more vulnerable to vascular stress and neurodegenerative diseases, such as Alzheimer’s.1

“Traditionally, we’ve focused on lowering average blood pressure numbers,” Trevor Lohman, MD, PhD, research assistant professor of neurology and gerontology at USC, said in a statement. “But this study suggests we should also be looking at how stable blood pressure is from moment to moment. Reducing these fluctuations could help protect the brain, even in people whose average readings look fine.”1

Nation and colleagues noted that future research will explore the effectiveness of blood pressure stabilizing interventions such as exercise, stress reduction, and tailored medication timing, could slow brain aging and reduce risk of dementia. Additionally, the team highlighted the cross-sectional nature of this study, emphasizing its inability to properly prove cause and effect.1

References

1. University of Southern California. Rapid blood pressure fluctuations linked to early signs of brain degeneration in older adults. Eurekalert!. October 29, 2025. Accessed October 31, 2025. https://www.eurekalert.org/news-releases/1103924

2. Lohman T, Shenasa F, Sible I, et al. Blood pressure dynamic instability and neurodegeneration in older adults. Journal of Alzheimer’s Disease. Published online October 17, 2025. doi:10.1177/13872877251386443