💬 Editorial by Holly Elser, MD, PhD, and Jonathan Graff-Radford, MD:
Recent randomized clinical trials on dementia prevention highlight several challenges in interpreting lifestyle intervention studies, including practice and Hawthorne effects, modest changes in cognitive outcomes, and heterogeneity in both trial design and participant baseline risk.
The trial by Zhang et al—evaluating aerobic exercise and intensive vascular risk reduction—showed no significant cognitive benefit over 2 years in older adults at elevated risk, underscoring the potential influence of midlife vs late-life intervention timing and the need for longer trials or biomarker-enriched cohorts to better assess dementia prevention strategies.
Dementia prevention is a global public health priority,1,2 with up to 45% of cases potentially attributable to modifiable risk factors over the life course.3 While recent landmark trials, including FINGER, SPRINT MIND, and POINTER, suggest either single-or multidomain lifestyle interventions can improve cognitive outcomes,4-6 others have shown no clear benefit,7,8 thus highlighting ongoing uncertainty in the field.
In this issue of JAMA Neurol ogy, Zhang and colleagues9 report the results of a single-blind, multicenter randomized clinical trial of the effects of exercise and intensive vascular risk reduction on cognitive function. Eligible study participants were between the ages of 60 and 85 years at baseline with a history of hypertension, family history of dementia, or self-reported cognitive decline. The study used a 2 × 2 factorial design wherein participants were randomized to aerobic exercise training alone, intensive pharmacological reduction of cardiovascular risk factors (IRVR) alone, both aerobic exercise and IRVR, or usual care for a 24-month period. The IRVR protocol lowered systolic blood pressure to less than 130 mm Hg, and participants with baseline serum low-density lipoprotein cholesterol (LDL-C) of 70 mg/dL or higher were also treated with a high-intensity statin.