Despite the non-significant differences between groups, a slight trend toward a dementia risk reduction has led to the Alzheimer’s Association providing funds for a follow-up extension trial, dubbed SPRINT-MIND 2.0.
Maria C. Carrillo, PhD
Despite early results suggesting a positive effect on the risk of dementia, the final analysis of the SPRINT-MIND trial has shown that implementing an intensive strategy to lower a patient’s systolic blood pressure to <120 mm Hg does not significantly reduce dementia risk compared to a standard care strategy.1
The trial showed that 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.
“Dementia continues to be a large public health challenge, and based on the primary results of this study, we still have yet to find an intervention strategy proven to reduce the risk of dementia,” Richard J. Hodes, MD, director of the National Institute on Aging (NIA), said in a statement.2
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.
For the MCI-only secondary outcome, the results were significantly different as well, with 14.6 cases per 1000 person-years in the intensive group and 18.3 cases per 1000 person-years in the standard group (HR, 0.81; 95% CI, 0.69 to 0.95; P
“For the clinician community, the main takeaway is that the mild cognitive impairment results of 19% reduced risk were so compelling,” Maria C. Carrillo, PhD, the chief science officer of the Alzheimer’s Association, told NeurologyLive
. “For us, as an organization, it's so important to share this information with the clinicians because, as they will know, when you prevent new cases of MCI, you're essentially preventing new cases of dementia. That's an important message not only for clinicians but also for the public at large.”
Notably, the investigators acknowledged that this is the first trial, to their knowledge, to show an intervention that significantly reduces the occurrence of MCI as well as the combined occurrence of MCI or dementia. Although, they did write that “some caution should be exercised in interpreting this result, both because MCI was not the primary cognitive outcome of the trial and because it is not clear what this effect may mean for the longer-term incidence of dementia.”
Laurie Ryan, PhD, chief of the Dementias of Aging Branch in the NIA Division of Neuroscience, explained in a statement that seeing a positive MCI result despite the study being cut short “makes these results encouraging.” In an accompanying editorial, Kristine Yaffe, MD, detailed that while “the SPRINT MIND study may not be the final approach for prevention of AD or other cognitive impairment,” it is indicative of “a major leap forward in what has emerged as a marathon” toward treating the disease.3
Another point of note made by study investigators, including principal investigator Jeff D. Williamson, MD, MHS, the chief of the Section on Geriatric Medicine and Gerontology at Wake Forest School of Medicine, was that due to the trial being terminated early, the study may not have been appropriately powered for its primary outcome. Williamson explained that "dementia takes longer to develop than MCI. Consequently, the early termination of the study likely affected the number of dementia cases detected."
Ultimately, there remains a need to further assess the SPRINT-MIND study participants, as it is possible that additional cases of probable dementia could possibly support a more definitive conclusion one way or the other. In that breadth, it was recently announced that a follow-up extension, dubbed SPRINT-MIND 2.0, will be conducted thanks in part to an $800,000 grant from the Alzheimer’s Association.4
That extension is expected to begin in early 2019, which will make results available approximately 1 year earlier than anticipated with other funding sources. According to the Alzheimer’s Association, discussions with other potential funders are ongoing.
“We're really excited about SPRINT-MIND 2.0 and the investigators in SPRINT-MIND were interested in additional follow-up for the individuals,” Carillo said. “We find the data to be compelling overall and saw that trend towards reducing the risk of dementia. Even though it was not definitive, it was a trend at 17% risk reduction for dementia, so we are committed as an organization to get clarity and certainty on that outcome by following a large group of the Sprint-MIND participants for a longer period of time. We’re hopeful that will give us more definitive results on the dementia outcome.”
1. 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.
2. Does intensive blood pressure control reduce dementia? [press release]. Bethesda, MD: National Institutes of Health; Published January 28, 2019. nih.gov/news-events/news-releases/does-intensive-blood-pressure-control-reduce-dementia. Accessed January 28, 2019.
3. Yaffe K. Prevention of cognitive impairment with intensive systolic blood pressure control. JAMA. Published online January 28, 2019. doi:10.1001/jama.2019.0008.
4. Alzheimer's Association funds two-year extension of the sprint mind study [press release]. Chicago, IL: Alzheimer’s Association. Published January 28, 2019. alz.org/news/2019/alzheimer-s-association-funds-two-year-extension-o. Accessed January 28, 2019.