Effect of Intensive Blood Pressure Control on Subtypes of Mild Cognitive Impairment and Risk of Progression From SPRINT Study

Sarah A. Gaussoin MS; Nicholas M. Pajewski PhD; Gordon Chelune PhD; Maryjo L. Cleveland MD; Michael G. Crowe PhD; Lenore J. Launer PhD; Alan J. Lerner MD; Jennifer Martindale-Adams EdD; Linda O. Nichols PhD; Paula K. Ogrocki PhD; Bonnie C. Sachs PhD; Kaycee M. Sink MD; Mark A. Supiano MD; Virginia G. Wadley PhD; Valerie M. Wilson MD; Clinton B. Wright MD; Jeff D. Williamson MD; David M. Reboussin PhD; Stephen R. Rapp PhD

Disclosures

J Am Geriatr Soc. 2022;70(5):1384-1393. 

In This Article

Results

A total of 9361 participants were randomized between November 2010 and March 2013 (Figure S3). Briefly, participants were a mean age of 67.9 years (SD, 9.4 years), with 28.2% of participants aged 75 years or older (Table S1). Randomized participants were 35.6% female, 30.0% black, and 10.5% Hispanic with a mean SBP at baseline of 139.7 mm Hg (SD, 15.6 mm Hg). Median scores at baseline for the MoCA, Logical Memory II, and Digit Symbol Coding were 23 (interquartile range [IQR], 20–26), 8 (IQR, 6–11), and 51 (IQR, 41–61), respectively.

Intervention Effects of MCI and its Subtypes

During follow-up, 4278 (91.4%) participants in the intensive treatment group completed at least one cognitive assessment, as compared with 4285 (91.5%) in the standard treatment group (Figure S3). Over a median follow-up of 5.06 years (interquartile range 3.82 to 5.96 years), 640 participants met the protocol definition of MCI, which required two consecutive adjudications of cognitive impairment. Table S2 displays the frequency of the initial and second adjudication for cases of MCI by subtype. Based on the first adjudication of MCI, the majority of cases were amnestic multi-domain (69.2%) or amnestic single domain (16.9%), whereas non-amnestic multi- and single-domain accounted for 6.8% and 7%, respectively. For those initially adjudicated as amnestic multi-domain, the majority were either adjudicated again as amnestic multi-domain at the second assessment (77.9%) or had progressed to probable dementia (14.5%). With respect to treatment group differences, MCI occurred in 287 participants in the intensive treatment group and 353 participants in the standard treatment group (14.6 vs. 18.3 per 1000 person-years, Hazard Ratio (HR), 0.81 [95% CI, 0.69–0.94], Figure 2), as reported previously. There was a similar beneficial effect of intensive treatment on the occurrence of amnestic subtypes of MCI (HR = 0.78; 95% CI, 0.66–0.92; p value = 0.003), as well as multi-domain subtypes of MCI (HR = 0.78, 95% CI, 0.65–0.93, p value = 0.007, Figure 3). In contrast, the occurrence of non-amnestic and single-domain subtypes of MCI was similar between the treatment groups.

Figure 2.

Occurrence of mild cognitive impairment by treatment group. Shaded regions indicate 95% confidence intervals

Figure 3.

Occurrence of subtypes of mild cognitive impairment by treatment group. Shaded regions indicate 95% confidence intervals

Transitions in Cognitive Status

As shown in Table S3, transitions indicative of progressive cognitive impairment were generally less frequent in the intensive treatment group. Participants randomized to intensive treatment less frequently transitioned from normal cognition to MCI (8.4% vs. 9.4%), and less frequently progressed from MCI to probable dementia (4.6% vs. 7.1%) compared with participants receiving standard treatment. Transitions from indeterminate adjudications represented a small proportion of transitions in both treatment groups (0.7% for both treatment groups). Table S4 examines model fit for the multistate survival model, comparing the observed versus expected prevalence of each cognitive state at various points of follow-up. The multistate model generally fit well through 4.5 years of follow-up, although it slightly overestimated the frequency of MCI and underestimated the frequency of death. Model fit was poorer at 5.25 years of follow-up, although this is not unexpected as this largely reflects the extended, observational follow-up period, when many participants were not accessed. The estimated 2-year transition probabilities from the multistate model are shown in Table 1. Overall, from a state of normal cognitive function, the most frequent transition was to MCI (estimated 2-year transition probability (P2 = 4.3%, 95% CI: 3.9% to 4.9%), with transitions to probable dementia (P2 = 0.6%, 95% CI: 0.5% to 0.9%) or death (P2 = 2.3%, 95% CI: 2.0% to 2.7%) being less frequent. From a state of MCI, the most likely transition was to intermittent MCI (P2 = 31.6%, 95% CI: 28.9% to 34.5%). Compared with a current status of normal cognitive function, the risk of transitioning to probable dementia or death was higher coming from MCI, with 2-year transition probabilities for probable dementia and mortality increasing to 5.9% (95% CI: 4.5%–7.7%) and 10.0% (95% CI: 8.3%–11.9%), respectively. Consistent with the overall trial results,[10] the risk of transitioning from normal cognitive function to MCI was lower with intensive treatment, although there were no other significant associations between treatment group and transition risk within the multistate model.

processing....