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Randomized Controlled Trial
. 2025 Jul;21(7):e70216.
doi: 10.1002/alz.70216.

Baseline cognition and demographic, lifestyle, and cardiovascular risk factors in US POINTER

Kathryn V Papp  1 , Sarah Tomaszewski Farias  2 , Marjorie Howard  3 , Amber Thro  4 , Tiia Ngandu  5   6 , Brad Caudle  4 , Bonnie C Sachs  4 , Michelle Chan  2 , Kristin R Krueger  7 , Elizabeth R T Hartman  8 , Athene Lee  9 , Michele K York  10 , Marie T Austin  4 , Kathryn E Demos  9 , Thomas M Holland  7 , Xiaoyan Leng  3 , Rema Raman  11 , Heather M Snyder  12 , Maria C Carrillo  12 , Rachel A Whitmer  13 , Mark A Espeland  3   4 , Laura D Baker  4 ; US POINTER Study Group
Affiliations
Randomized Controlled Trial

Baseline cognition and demographic, lifestyle, and cardiovascular risk factors in US POINTER

Kathryn V Papp et al. Alzheimers Dement. 2025 Jul.

Abstract

Introduction: Validation of the primary cognitive composite and baseline cognitive characteristics are presented for the US-Study-to-Protect-Brain-Health-Through-Lifestyle-Intervention-to-Reduce-Risk (US POINTER).

Methods: US POINTER is a multicenter, randomized clinical trial of two lifestyle interventions testing cognitive benefit in older adults without significant cognitive impairment but at-risk for decline due to well-established factors. Cognition is measured using a global cognitive composite (US POINTER modified Neuropsychological Test Battery-PmNTB).

Results: The PmNTB is a valid cognitive composite, exhibiting good psychometric properties and tracking with other established outcomes. Among the 2111 enrolled participants (mean age = 68.2 years, 69% women, 31% from race and ethnic minoritized groups), demographic characteristics alone (age, sex, education, race, ethnicity) explained more variance in cognition measured using the PmNTB (25.94%) compared with cardiovascular and family history risk factors combined (added < 3% explained variance).

Discussion: In a large diverse older adult cohort, demographic features rather than well-established risks for cognitive decline correlate with baseline global cognition.

Clinical trial registration number: NCT03688126 HIGHLIGHTS: Demographic characteristics explain baseline cognition in at-risk older adults. The POINTER Modified Neuropsychological Test Battery (PmNTB) is a valid measure. Worse cognition tracks with E4+, high HbA1c, current smoking, Framingham heart risk.

Keywords: clinical trials; healthy aging; lifestyle interventions; risk factors.

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Conflict of interest statement

US POINTER was conceived and developed in partnership with the Alzheimer's Association. Drs. Snyder and Carrillo, full‐time employees of the Alzheimer's Association, have contributed to the study design, trial oversight, manuscript preparation, and the decision to submit the article for publication. The authors have no conflicts to report. Author disclosures are available in the Supporting Information.

Figures

FIGURE 1
FIGURE 1
Associations between the PmNTB and other composites (FINGER NTB, PACC5). PmNTB, US POINTER Modified Neuropsychological Test Battery.
FIGURE 2
FIGURE 2
Summary of associations between global cognition and risk factors (demographic‐adjusted). Note: Panel A represents risk factors that were part of study inclusion criteria and Panel B represents risk factors not explicitly selected for at study entry. Boxed risk factors are statistically significant.
See this image and copyright information in PMC

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