Relative impact of multidomain lifestyle interventions on deficit accumulation frailty over 24 months in the U.S. POINTER trial

Authors

• Mark A. Espeland, Wake Forest University School of Medicine, Department of Internal Medicine, Winston-Salem, NC, 27157.Follow
• KayLoni Olson, Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence RI, 02912 and The Miriam Hospital, Providence, RI, 02906.
• Christy C. Tangney, Rush University Medical Center, Department of Clinical Nutrition, Chicago, IL, 60612.
• Darren R. Gitelman, Advocate Health - MidwestFollow
• MaryJo Cleveland, Wake Forest University School of Medicine, Department of Internal Medicine, Winston-Salem, NC, 27157.
• Amber A. Thro, Wake Forest University School of Medicine, Department of Internal Medicine, Winston-Salem, NC, 27157.
• Yitbarek N. Demesie, Wake Forest University School of Medicine, Division of Public Health Sciences, Winston-Salem, NC, 27157.
• Heather M. Snyder, Alzheimer's Association, Medical and Scientific Relations, Chicago, IL, 60601.
• Rachel A. Whitmer, University of California Davis, Department of Public Health Sciences, Sacramento, CA, 95616.
• Pankaja Desai, Rush University Medical Center, Department of Clinical Nutrition, Chicago, IL, 60612.
• Rifat Alam, University of California Davis, Department of Public Health Sciences, Sacramento, CA, 95616.
• Lucia Crivelli, Department of Cognitive Neurology, Fleni, Buenos Aires, Argentina.
• Thomas M. Holland, Rush University Medical Center, Department of Internal Medicine, Chicago, IL, 60612.
• Olivia Preissle, Alzheimer's Association, Chicago, IL, 60601.
• Rema Raman, Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, 92121.
• Michele K. York, Wake Forest University School of Medicine, Department of Internal Medicine, Winston-Salem, NC, 27157.
• Laura D. Baker, Wake Forest University School of Medicine, Department of Internal Medicine, Winston-Salem, NC, 27157.

Recommended Citation

Espeland MA, Olson K, Tangney CC, et al. Relative Impact of Multidomain Lifestyle Interventions on Deficit Accumulation Frailty Over 24 Months in the U.S. POINTER Trial. J Gerontol A Biol Sci Med Sci. Published online April 6, 2026. doi:10.1093/gerona/glag094

Affiliations

Advocate Aurora Research Institute, Advocate Lutheran General Park Ridge, Wake Forest University School of Medicine

Abstract

Background: Multidomain lifestyle interventions hold promise as approaches to slow aging. Deficit accumulation frailty indices (FIs) are increasingly used to capture aging processes. Frailty is highly associated with increased mortality and chronic disease risk but the degree to which multidomain lifestyle changes impact frailty is not clear.

Methods: The U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) was a 2-year randomized clinical trial to compare two multidomain lifestyle interventions designed to increase exercise, improve diet, and promote social and cognitive stimulating activities and health monitoring. The Structured intervention incorporated greater structure, intensity, and accountability than the Self-Guided intervention. A modified FI (mFI) was developed from data collected at baseline, 12, and 24 months.

Results: The trial enrolled 2,111 adults (ages 60-79 years) who were at increased risk for accelerated cognitive decline. At 24 months, the mean (standard error) changes from baseline of a 31-component mFI were -0.009 (0.002) for Self-Guided and -0.024 (0.002) for Structured participants, a difference averaging -0.014 [-0.019, -0.008] (p < 0.0001). Group differences were similar across subgroups based on age, sex, body mass index, diabetes, and baseline mFI. Changes in mFI did not account for the relative cognitive benefits provided by the Structured intervention compared to the Self-Guided intervention.

Conclusions: Multidomain lifestyle interventions may decrease frailty and slow aging processes with greater structure and intensity resulting in greater benefits.

Clinicaltrials.gov identifier: ClinicalTrials.gov Identifier: NCT03688126.

Type

Article

PubMed ID

41950390