When compared with placebo, a polypill (antihypertensives and a statin) targeting vascular risk factors may reduce functional, but not cognitive, decline in individuals aged 65 years and older, according to study findings published in JAMA Neurology.
Previous studies have correlated vascular risk factors such as hypertension, dyslipidemia, and impaired fasting glucose levels with a heightened risk for cognitive decline, but very few studies have analyzed the effect of modifying vascular risk factors on functional status.
To determine if a polypill could reduce cognitive and functional decline in people with vascular risk factors, researchers in 86 centers across 8 countries conducted a randomized clinical trial, International Polycap Study 3 (TIPS-3), between June 30, 2012 and September 30, 2020. Out of 5713 study participants, 2389 (42%) were aged 65 years and older with an intermediate risk for cardiovascular disease.
The researchers randomly assigned these participants into 4 different treatment groups: a polypill plus aspirin group, a polypill plus placebo group, an aspirin plus placebo group, and a double placebo group. The polypill treatment consisted of a daily combination of 100 mg of atenolol, 10 mg of ramipril, 25 mg of hydrochlorothiazide, and 40 mg of simvastatin. The aspirin treatment consisted of 75 mg of aspirin daily.
Of the 2389 individuals aged 65 years and older, 2098 (88%; 60% women; mean age, 70.1 years) completed both a baseline and at least 1 follow-up assessment, including:
- the Montreal Cognitive Assessment (MoCA) to evaluate for mild cognitive impairment,
- the Digit Symbol Substitution Test (DSST) to assess attention, psychomotor speed, and executive function,
- the Trail Making Test Part B (TMT-B) to assess attention, and
- the Standard Assessment of Global Everyday Activities (SAGEA) to assess functional status.
The researchers combined all these outcome measure scores into a composite score, indicating both cognitive and functional decline.
After an average follow-up of 5 years, the researchers did not observe any significant difference in terms of composite cognitive and functional decline when comparing the 3 treatment groups to the double placebo group.
Approximately 356 individuals in the polypill only group experienced substantial decline at a rate of 6.52 per 100 patient-years, whereas 328 individuals in the double placebo group experienced substantial decline at a rate of 6.34 per 100 patient-years (hazard ratio [HR], 1.05; 95% CI, 0.90-1.21; P =.55). They found comparable results when assessing the aspirin only and aspirin plus polypill treatment groups to the double placebo group.
In contrast, when just looking at functional status alone, participants in the polypill only and polypill plus aspirin treatment groups both demonstrated reduced functional decline compared with the double placebo group (mean country-standardized adjusted follow-up SAGEA scores, 0.06 vs 0.15; P =.01 and 0.01 vs 0.14; P =.01)
Overall, the findings suggest vascular risk factor modification could potentially slow functional decline, but not cognitive decline, in older adults.
The researchers do emphasize that “Larger studies with longer follow-up may be warranted to detect small changes in cognition that may still be relevant at a population level. Use of functional assessments may be a more sensitive outcome measure in international studies.”
Study limitations included lack of study power to detect small changes in cognition and function, potential responder bias, lack of proper measurement of decline in cognitive status, potential lack of generalizability of Western outcome measures to global populations, and the effects of physical decline on functional status.
Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.
Bosch JJ, O’Donnell MJ, Gao P, et al. Effects of a polypill, aspirin, and the combination of both on cognitive and functional outcomes: a randomized clinical trial. JAMA Neurol. Published online January 30, 2023. doi:10.1001/jamaneurol.2022.5088