Anticholinergic Use Linked to Faster Physical Decline in Older Adults, finds research
Researchers have found in a new cohort study that higher exposure to anticholinergic medications was associated with an accelerated decline in physical performance. This decline was clinically meaningful, highlighting the importance of minimizing anticholinergic use to support healthy aging. The study was published in JAMA Network by Shelly L. and colleagues.
The research was performed in the Adult Changes in Thought (ACT) study, a longitudinal population-based cohort from Kaiser Permanente Washington. Data were accrued from February 1994 through March 2020, and analysis was between January 2023 and December 2024. There were 4283 participants aged 65 years or more included in the analysis. Eligibility criteria included having at least two study visits and a minimum of 10 years of enrollment before the study index date. Of the total sample, 4210 individuals (58.6% women, mean age 74.3 years) were included in the gait speed analysis, while 4200 (58.5% women, mean age 74.5 years) contributed to the grip strength evaluation. The average follow-up time was 8.2 years.
The investigators assessed anticholinergic exposure in multiple dimensions. Two traditional measures presumed constant effects of constant exposure:
• 10-year Total Standardized Daily Dose (TSDD)
• 2-year mean Standardized Daily Dose (mSDD)
The study also used WCE models to account for time-varying effects over varying windows (2, 4, 6, 8, or 10 years). These models were intended to express the dynamic interaction between exposure duration and physical deterioration. The main outcomes were gait speed (meters per second) and grip strength (kilograms). Generalized Estimating Equations (GEE) adjusted linear models compared the rate of decline by exposure group, and model fit was examined with the quasi-information criterion (QIC).
Key Findings
• Relative to nonusers, individuals with TSDD ≥1096 over 10 years had a significantly larger decrease in gait speed of −0.0132 m/s per year (95% CI, −0.0193 to −0.0070).
• Individuals with 2-year mSDD ≥0.5 walked more slowly with a reduction of −0.0101 m/s per year (95% CI, −0.0174 to −0.0029).
• The 4-year WCE model most fully explained gait speed decline and indicated that a 1-unit weighted mSDD increase was associated with a −0.0034 m/s per year (95% CI, −0.0048 to −0.0019) decline in gait speed.
• Grip strength was not substantially affected under standard exposure models.
• But the 6-year WCE model of grip strength had a decrease of −0.0329 kg per year (95% CI, −0.0612 to −0.0046) for each unit rise in weighted mSDD, indicating a postponed but significant effect on muscle strength.
This cohort study identified that increased anticholinergic exposure was linked with faster physical decline, namely reduced gait speed and weaker grip strength. Health care practitioners can take steps to minimize or replace such medications when feasible to facilitate healthier aging outcomes.
Reference:
Gray SL, Su Y, Eshetie TC, LaCroix AZ, Marcum ZA, Yu O. Cumulative Anticholinergic Exposure and Change in Gait Speed and Grip Strength in Older Adults. JAMA Netw Open. 2025;8(7):e2519819. doi:10.1001/jamanetworkopen.2025.19819
