Intensive Blood Pressure Lowering Significantly Decreases Hippocampal Volume

Ilya M Nasrallah, MD, PhD

Data from a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT-MIND; NCT01206062) revealed that intensive blood pressure treatment with systolic goal of less than 120 mm Hg was associated with a small but statistically significant greater decrease in hippocampal volume compared with standard treatment with a systolic blood pressure goal of less than 140 mm Hg.¹

The results were consistent with the observation that intensive treatment is associated with greater decreases in total brain volume. In total, the mean hippocampal volume decreased from 7.45 cm3 to 7.39 cm3 (difference, ­–0.06 cm3 [95% CI, ­–0.08 to –0.04]) in the intensive treatment group (n = 356) compared to 7.48 cm3 to 7.46 cm3 (difference, –0.02 cm3 [95% CI, –0.05 to –0.003]) in the standard treatment group (n = 317; between-group difference in change, –0.033 cm3 [95% CI, –0.062 to –0.003]; P = .03).

Lead author Ilya M Nasrallah, MD, PhD, assistant professor of radiology, Hospital of the University of Pennsylvania, and colleagues recruited 673 patients who had baseline magnetic resonance imaging (MRI), 454 of which completed the 4-year follow-up at a median of 3.98 (interquartile range [IQR], 3.7-4.1) years after randomization.

There were no significant between-group differences for the other 2 structural biomarkers, SPARE-AD score and meta-ROI mean cortical thickness. Additionally, researchers noticed a decline in mean absolute and relative cerebral blood flow (CBF) in the posterior cingulate gyrus during follow-up, but there were no significant differences between treatment groups.

READ MORE: Intra-Cellular Therapies Expands Pipeline With ITI-1284 to Treat Dementia-Related Psychosis

Secondary biomarkers associated with vascular disease such as frontal gray matter were significantly decreased in the intensive treatment group (mean difference, –1.06 cm3 [95% CI, –1.95 to –0.16]; P = .02), but there were no between groups differences observed.

Participants aged 75 and older tended to exhibit larger changes in the most Alzheimer disease (AD)-related biomarker changes compared with those younger than 75 years. Specifically, they demonstrated larger decreases in hippocampal volumes and larger increases in SPARE-AD scores.

"In conclusion, there was no consistent evidence of a difference in the progression of AD-related neurodegeneration between intensive and standard blood pressure control. Beyond the previously reported favorable effect on WML volume, there was also no consistent association with other putative biomarkers of cerebrovascular disease, and the differences between groups in all of these MRI biomarkers were small,” Nasrallah et al noted.

Nominally significant interactions with respect to sex for mean cortical thickness (men: 0.035 [95% CI, –0.007 to 0.076]; women: –0.022 [95% CI, –0.054 to 0.010]; P = .03) and relative mean CFB in the posterior cingulate gyrus relative to putamen (men: –0.11 [95% CI, –0.21 to –0.01]; women: 0.03 [95% CI, –0.05 to 0.11]; P= .03) were observed.

The final analysis of the SPRINT-MIND trial was published in January 2019 and showed that implementing an intensive treatment strategy does not significantly reduce dementia risk compared to standard care.²

In the intensive treatment group (n = 4678), there were 7.2 cases of probable dementia per 1000 person-years (149 cases), compared to 8.6 cases per 1000 person-years (176 cases) in the standard treatment group (n = 4683), over the total median follow-up of 5.11 years (hazard ratio [HR], 0.83 [95% CI, 0.67 to 1.04]). In total, 9361 participants with a mean age of 67.9 years were randomized to either the intensive group or the standard treatment group.

Although the trial was not successful in its primary outcome, a secondary composite outcome of mild cognitive impairment (MCI) or probably dementia was shown to be significantly different between groups, in favor of the intensive treatment group (HR, 0.85 [95% CI, 0.74 to 0.97]; P = .01). There were 20.2 cases per 1000 person-years in the intensive group compared to 24.1 per 1000 person-years in the standard group.

REFERENCES

1. Nasrallah IM, Gaussoin SA, Pomponio R, et al. Association of intensive vs standard blood pressure control with magnetic resonance imaging biomarkers of Alzheimer disease: secondary analysis of the SPRINT MIND randomized trial. JAMA Neurol. Published online March 8, 2021. doi: 10.1001/jamaneurol.2021.0178.

2. Williamson JD, Pajewski NM, Auchus AP, et al. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA. Published online January 28, 2019. doi: 10.1001/jama.2018.21442.