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In A Nutshell
- A two-year clinical trial found no significant cognitive improvement from exercise or intensive heart-risk treatment.
- Experts say preventing dementia may require broader lifestyle changes beyond exercise and medication alone.
- Participants still saw physical health benefits, including lower blood pressure and better fitness.
- Small gains in test scores likely came from practice effects, not the interventions.
For millions of aging Americans worried about losing their mental sharpness, the advice has long been stay active, keep blood pressure in check, and watch your cholesterol. But a large clinical trial across four U.S. sites that tracked participants for two years has delivered a frustrating result. None of those strategies, alone or combined, led to clear improvements in thinking ability compared to usual care.
The study, known as the Risk Reduction for Alzheimer’s Disease (rrAD) trial, enrolled 513 older adults between the ages of 60 and 85 who were considered at higher risk for dementia. Some had a family history of the disease, some reported noticing their own thinking getting fuzzier, and some had high blood pressure. Researchers randomly assigned them to one of four groups: an aerobic exercise program, aggressive medication to lower blood pressure and cholesterol, a combination of both, or standard care from their own doctors. After two full years, the researchers found no statistically meaningful differences in thinking ability among any of the groups.
The results, published online in JAMA Neurology, push back against a widely held assumption that tackling well-known heart-health risk factors will also protect the brain. While earlier observational research has linked physical activity and controlled blood pressure to sharper thinking in later life, this carefully designed experiment suggests the relationship may not be so straightforward, at least not over a two-year window.
How the Exercise and Medication Study Worked
Led by Rong Zhang, a researcher at the Institute for Exercise and Environmental Medicine at Texas Health Presbyterian Hospital Dallas, the trial split participants into four equally sized groups. That allowed researchers to examine the effects of exercise on its own, medication on its own, both together, and neither.
Participants assigned to the exercise groups gradually ramped up to about 160 minutes per week of moderate-to-hard aerobic activity, such as brisk walking or cycling, over the first six months, then maintained that level for the remaining 18 months. Intensity was tailored to each person based on a treadmill fitness test at the start of the trial.
Those in the intensive medication groups received blood-pressure-lowering drugs with the goal of pushing the top number of their blood pressure reading below 130. Participants whose “bad” cholesterol was at or above 70 mg/dL also received a high dose of atorvastatin, a common cholesterol-lowering drug. The combination group got both the exercise program and the medications, while the usual-care group simply followed their regular doctor’s recommendations and was encouraged to do gentle stretching and balance exercises at a similar frequency.
Sticking with the program was not an issue for most people. The median adherence rate for exercise was 91 percent in the exercise-only group and 85 percent in the combined group. Medication adherence ranged from 87 to 89 percent across the relevant groups.
What Cognitive Tests Revealed About Exercise and Dementia Risk
Every six months for two years, trained staff gave participants a set of cognitive tests. The primary measure was a combined score designed to pick up early signs of Alzheimer’s-related decline. It bundled together tests of memory, attention, and processing speed into a single number. A secondary measure focused on the mental skills involved in planning, focusing, and juggling multiple tasks.
At the 24-month mark, scores on the primary measure inched up slightly across all groups, by 0.2 to 0.3 units on a standardized scale, but there were no meaningful differences between those who exercised and those who did not, or between those on intensive medication and those who were not. The same held true for every individual test within both sets of measures. Every group improved a little, and no group improved more than any other.
The medications did accomplish what they were designed to do on the heart-health front. Blood pressure dropped by about 13 points in the intensive medication group compared to roughly 8 points in those not receiving the aggressive treatment. Cholesterol fell by about 24 mg/dL in the medication group versus about 7 mg/dL in those without it. Exercise also delivered a measurable physical benefit: participants who worked out maintained their aerobic fitness over the two years, while those who did not saw a small decline. Yet none of these body-level improvements translated into better thinking skills.
Why Exercise and Medication May Not Have Improved Cognition
The researchers themselves offered several possible explanations. The sample size, while substantial at 513, may not have been large enough to detect the small cognitive effects suggested by earlier research. The trial was originally planned for 640 participants but was scaled back to 510 to meet enrollment timelines. The actual difference in blood pressure between the medication and non-medication groups was only about 5 points, and the cholesterol gap was about 17 mg/dL. Those margins may simply have been too narrow to nudge brain function.
The cognitive tests themselves may also not have been sensitive enough to pick up subtle changes over just two years, particularly in people who had not yet developed dementia. The researchers noted that the small improvements seen across all groups likely reflected either a “practice effect,” meaning people got better at a test simply by taking it multiple times, or an “expectancy effect,” where people perform a bit better just because they know they are part of a study.
The trial also collided with the COVID-19 pandemic. Between October 2020 and May 2021, some testing had to be conducted remotely, and exercisers shifted to home or outdoor workouts. While the researchers included those remote test results in their analysis, the disruption could have introduced inconsistency.
The researchers did not conclude that exercise or blood pressure control are useless for brain health. They pointed to other major studies, including the FINGER trial and the recently completed US POINTER study, that found cognitive benefits from programs combining exercise with diet changes, cognitive training, and monitoring of health risks. The rrAD trial tested exercise and medication in isolation or together but did not include dietary changes or brain-training activities.
They also drew a careful distinction between improving cognitive test scores and preventing dementia itself. The SPRINT MIND study and a more recent trial in rural China both found that aggressive blood pressure lowering reduced the rate of dementia diagnoses over time, a different and arguably more important outcome. The rrAD trial was not designed to measure dementia rates.
Current American Heart Association and American College of Cardiology guidelines already recommend lowering blood pressure below 130 to help prevent cognitive problems and dementia. Both the treatment and control arms of the rrAD trial achieved that target, which may help explain why no group pulled ahead.
The safety profile was reassuring. A total of 107 serious side effects occurred across all groups at similar rates, with only 8 classified as related or possibly related to the study. Those were all resolved without lasting problems. Two deaths occurred during the trial, neither related to the study treatments.
What the rrAD trial suggests is that protecting an aging brain is likely more involved than any single prescription, whether that prescription is a pair of running shoes or a pill bottle. Longer trials, larger groups of participants, and combined lifestyle approaches that go beyond exercise and medication may be needed to find the formula that truly keeps cognitive decline at bay.
Disclaimer: This article is based on findings from a single clinical trial with a limited sample size and two-year follow-up period, and does not conclude that exercise or cardiovascular treatment are ineffective for long-term brain health. It is intended for informational purposes only and should not be taken as medical advice. Consult a qualified healthcare provider before making any changes to your exercise routine, medications, or dementia prevention strategy.
Paper Notes
Limitations
The researchers acknowledged several limitations. The sample size may have been too small, having been reduced from an originally planned 640 participants to 510 during the trial. The differences achieved in blood pressure (approximately 5 mm Hg) and cholesterol (approximately 17 mg/dL) between the intensive medication and non-medication groups may not have been large enough to produce cognitive benefits. The study did not use brain imaging or blood-based markers to identify participants with underlying Alzheimer’s-related brain changes, which could have improved the study’s ability to detect treatment effects. The COVID-19 pandemic forced some testing to be conducted remotely and disrupted exercise routines. Additionally, the cognitive tests used may not have been sensitive enough to differentiate subtle age-related decline from improvement over a 24-month period, and observed improvements across all groups likely reflected practice or expectancy effects.
Funding and Disclosures
The project was funded by US National Institutes of Health grant R01 AG049749, with additional funding from the Josephine Hughes Sterling Foundation. The funders had no role in the design, conduct, data analysis, manuscript preparation, or decision to publish. Multiple authors reported disclosures: Dr. Zhang reported grants from the Josephine Hughes Sterling Foundation and the NIH during the study. Dr. Vidoni reported grants from the National Institute on Aging, personal fees from external advisory and data safety monitoring committees at several universities, and a patent for measuring cerebral blood flow changes. Dr. Vongpatanasin reported personal fees from AstraZeneca and Clinical Education Alliance. Dr. Kerwin reported contracted clinical research from Acumen, Amylyx, Bristol Myers Squibb, Merck, and Roche, and research and advisory board fees from Eli Lilly. Several other authors reported NIH grants during the conduct of the study.
Publication Details
Title: Effects of Exercise and Intensive Vascular Risk Reduction on Cognitive Function in Older Adults: A Randomized Clinical Trial | Authors: Rong Zhang, PhD; Eric Vidoni, PhD; Wanpen Vongpatanasin, MD; et al | Journal: JAMA Neurology | Published Online: March 23, 2026 | DOI: 10.1001/jamaneurol.2026.0359 | Trial Registration: ClinicalTrials.gov Identifier: NCT02913664 | Corresponding Author: Rong Zhang, PhD, Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas
Perhaps cognitive decline is just part of getting old? Diet and exercise are good for the physical body, but perhaps not that important to the brain’s functions. So continue to drink scotch and take afternoon naps.