More intensive BP lowering may not impact progression of Alzheimer’s disease

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More intensive BP lowering may not impact progression of Alzheimer’s disease

Intensive BP reduction in hypertension was associated with greater changes in hippocampal volume, but not any other MRI biomarkers for Alzheimer’s disease, compared with standard treatment, according to data published in JAMA Neurology.

Ilya M. Nasrallah

“The main takeaway is that while various individual measures appeared more favorable in either the intensive or standard BP treatment groups, we did not see a consistent effect showing a difference in Alzheimer’s disease or vascular disease biomarkers that is likely to be clinically significant in the time frame of the SPRINT study, which was 4 years,” Ilya M. Nasrallah, MD, PhD, assistant professor of radiology at the Hospital of the University of Pennsylvania, told Healio. “Some knowledge gaps prior to this work regarded whether there were measurable positive or adverse effects on Alzheimer’s disease or vascular disease related to intensive blood pressure intervention. Prior to SPRINT, there was consensus that treating hypertension was beneficial, however there was no consensus on whether intensive therapy would add further benefit or might itself start to cause injury. Our study suggests that we do not see that differential effects on either pathology point to a clear benefit for brain health or any clear adverse risk for the intensive therapy.”

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The SPRINT MIND trial

As Healio previously reported, in the main results of SPRINT MIND, intensive BP control failed to reduce risk for the primary outcome of probable dementia in participants with hypertension but led to a risk reduction for the secondary outcomes of mild cognitive impairment and a composite of mild cognitive impairment or probable dementia.

For this substudy of the SPRINT MIND trial, researchers assessed the effect of intensive BP control on Alzheimer’s disease-related brain biomarkers.

The researchers included 673 patients with a baseline MRI (mean age, 67 years; 40% women; 32% Black), of whom 454 completed the 4-year follow-up MRI. During the 4-year period, participants were randomly assigned to intensive BP treatment with a systolic BP goal of less than 120 mm Hg or standard treatment with a goal of less than 140 mm Hg. All participants were aged at least 50 years, had hypertension and had no history of diabetes or stroke. The main outcomes were changes in hippocampal volume, measures of Alzheimer’s disease regional atrophy, posterior cingulate cerebral blood flow and mean fractional anisotropy in the cingulum bundle.

Researchers reported that within the intensive treatment group, mean hippocampal volume changed by 0.06 cm³ (95% CI, 0.08 to 0.04) compared with a mean 0.02 cm³ (95% CI, 0.05 to 0.003) in the standard treatment group (between-group difference, 0.033 cm³; 95% CI, 0.062 to 0.003; P = .03).

However, researchers observed no between-group differences for measures of Alzheimer’s disease regional atrophy, cerebral blood flow or mean fractional anisotropy.

“Rather, the benefit may have less to do with direct effects on brain pathology and function and more to do with removing barriers for performance that are placed by systemic disease that could otherwise accelerate clinical decline.” Nasrallah told Healio. “The major gap that remains is that we do not know the long-term effects of intensive vs. standard therapy. Hypertension, Alzheimer’s disease and cerebrovascular disease all progress over time frames much longer than the SPRINT study, and it is possible that longer-term intervention may show some effect.”

Link ‘still elusive’

“The complex pattern of findings across multiple studies suggests that the mechanistic link between cardiovascular health and Alzheimer’s disease is still elusive,” Susan M. Landau, PhD, and Theresa M. Harrison, PhD, of the Helen Wills Neuroscience Institute at the University of California in Berkeley, wrote in a related editorial. “Intensive hypertension control was linked to some worse outcomes (eg, total brain and hippocampal volume decreases and poorer processing speed) and to some benefits (an improvement in white matter hyperintensities and reduced incidence of mild cognitive impairment), but intervention groups do not differ for most measures reported in the SPRINT MIND cognitive and MRI substudies.

“The findings of the SPRINT study overall suggest that the primary benefit of intensive hypertension control is in reducing cardiovascular events,” Landau and Harrison wrote. “But the SPRINT MIND data thus far do not point to a clear additional benefit of such treatment in maintaining cognitive function or reducing the risk of Alzheimer’s disease. Future work is needed to understand how Alzheimer’s disease and cerebrovascular pathophysiology contribute to the complex relationship between cardiovascular health and cognitive decline.”

For more information:

• Ilya M. Nasrallah, MD, PhD, can be reached at ilya.nasrallah@pennmedicine.upenn.edu.

Reference:

• Landau SM, et al. JAMA Neurol. 2021;doi:10.1001/jamaneurol.2021.0083.