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Randomized Controlled Trial
. 2024 Jan 1;184(1):54-62.
doi: 10.1001/jamainternmed.2023.6279.

Effect of Personalized Risk-Reduction Strategies on Cognition and Dementia Risk Profile Among Older Adults: The SMARRT Randomized Clinical Trial

Kristine Yaffe  1   2   3   4 , Eric Vittinghoff  2 , Sascha Dublin  5 , Carrie B Peltz  4 , Lynn E Fleckenstein  5 , Dori E Rosenberg  5 , Deborah E Barnes  2   3 , Benjamin H Balderson  5 , Eric B Larson  6
Affiliations
Randomized Controlled Trial

Effect of Personalized Risk-Reduction Strategies on Cognition and Dementia Risk Profile Among Older Adults: The SMARRT Randomized Clinical Trial

Kristine Yaffe et al. JAMA Intern Med. .

Abstract

Importance: Modifiable risk factors are hypothesized to account for 30% to 40% of dementia; yet, few trials have demonstrated that risk-reduction interventions, especially multidomain, are efficacious.

Objective: To determine if a personalized, multidomain risk reduction intervention improves cognition and dementia risk profile among older adults.

Design, setting, and participants: The Systematic Multi-Domain Alzheimer Risk Reduction Trial was a randomized clinical trial with a 2-year personalized, risk-reduction intervention. A total of 172 adults at elevated risk for dementia (age 70-89 years and with ≥2 of 8 targeted risk factors) were recruited from primary care clinics associated with Kaiser Permanente Washington. Data were collected from August 2018 to August 2022 and analyzed from October 2022 to September 2023.

Intervention: Participants were randomly assigned to the intervention (personalized risk-reduction goals with health coaching and nurse visits) or to a health education control.

Main outcomes and measures: The primary outcome was change in a composite modified Neuropsychological Test Battery; preplanned secondary outcomes were change in risk factors and quality of life (QOL). Outcomes were assessed at baseline and 6, 12, 18, and 24 months. Linear mixed models were used to compare, by intention to treat, average treatment effects (ATEs) from baseline over follow-up. The intervention and outcomes were initially in person but then, due to onset of the COVID-19 pandemic, were remote.

Results: The 172 total participants had a mean (SD) age of 75.7 (4.8) years, and 108 (62.8%) were women. After 2 years, compared with the 90 participants in the control group, the 82 participants assigned to intervention demonstrated larger improvements in the composite cognitive score (ATE of SD, 0.14; 95% CI, 0.03-0.25; P = .02; a 74% improvement compared with the change in the control group), better composite risk factor score (ATE of SD, 0.11; 95% CI, 0.01-0.20; P = .03), and improved QOL (ATE, 0.81 points; 95% CI, -0.21 to 1.84; P = .12). There were no between-group differences in serious adverse events (24 in the intervention group and 23 in the control group; P = .59), but the intervention group had greater treatment-related adverse events such as musculoskeletal pain (14 in the intervention group vs 0 in the control group; P < .001).

Conclusions and relevance: In this randomized clinical trial, a 2-year, personalized, multidomain intervention led to modest improvements in cognition, dementia risk factors, and QOL. Modifiable risk-reduction strategies should be considered for older adults at risk for dementia.

Trial registration: ClinicalTrials.gov Identifier: NCT03683394.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Yaffe reported serving on Data Safety and Monitoring Boards for the National Institutes of Health and industry sponsored trials, as a board member of Alector, and on scientific advisory boards for the Global Council on Brain Health and Alpha Cognition. Dr Vittinghoff reported salary from the National Institutes of Health for statistical analysis during the conduct of the study. Dr Dublin reported grants from GlaxoSmithKline and other support from Syneos Health for work related to long-acting opioid safety outside the submitted work. Dr Barnes reported being co-founder and chief science adviser for Together Senior Health, which is testing an online, 12-week Brain Health Together program to maintain cognitive function and reduce dementia risk in older adults with cognitive decline; the University of California, San Francisco Conflict of Interest Advisory Committee determined that this relationship does not represent a conflict of interest with this study. Dr Balderson reported grants from National Institutes of Health and the Centers for Disease Control and Prevention outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Recruitment Flow for the Systematic Multi-Domain Alzheimer Risk Reduction Trial (SMARRT)
Figure 2.
Figure 2.. Prevalence and Combination of Risk Factors for the 172 Participants in the Systematic Multi-Domain Alzheimer Risk Reduction Trial
Darker shading indicates higher frequency of individual risk factors (blue) or risk factor combinations (red).
Figure 3.
Figure 3.. Primary and Secondary Outcomes
Primary (A) and secondary (B and C) outcomes in the Systematic Multi-Domain Alzheimer Risk Reduction Trial by treatment group. ATE indicates average treatment effect. Error bars represent 95% CIs.
See this image and copyright information in PMC

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