CHICAGO — Combined lifestyle interventions may improve cognition more than antiamyloid monoclonal antibodies (MABs) in patients with early Alzheimer’s disease (AD) or mild cognitive impairment (MCI).

A review of randomized trials showed that lifestyle interventions improved cognitive scores, whereas MABs primarily slowed decline.

“Lifestyle interventions are simple but powerful,” lead investigator Majid Fotuhi, MD, PhD, adjunct professor of neuroscience at the Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University in Baltimore, told Medscape Medical News.

“These interventions can significantly modify the brain anatomy and biology and reduce cognitive decline linked to aging. We need to treat them as powerful therapeutic interventions, not just add-on supplements to medications,” he added.

The findings were presented on April 22 at American Academy of Neurology (AAN) 2026 Annual Meeting.

Meds vs Lifestyle

AD is increasingly recognized as a multifactorial condition influenced by modifiable lifestyle factors such as physical activity, diet, sleep, and social engagement. At the same time, MABs that target amyloid have demonstrated the ability to reduce Alzheimer’s pathology and modestly slow cognitive decline. However, they have not been shown to improve cognition and are associated with cost and safety considerations.

To compare the relative effects of multimodal lifestyle interventions and MABs on cognitive outcomes, investigators conducted a review of randomized controlled trials.

The review included five randomized controlled trials of lifestyle interventions and three large phase 3 trials of MABs. Across studies, participants were typically aged 71-73 years and had MCI or early-stage AD, with Mini-Mental State Examination scores of 24-26 and no significant comorbidities.

All trials reported outcomes using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and included a control group.

The lifestyle trials, which included between 25 and 120 participants, evaluated interventions such as exercise and cognitive training, with some also incorporating social engagement, a plant-based diet, and stress reduction. However, the type, intensity, and frequency of these interventions varied across studies, Fotuhi noted.

In contrast, the MABs trials enrolled thousands of participants and required evidence of amyloid pathology on PET imaging.

In randomized trials of multimodal lifestyle interventions, the study revealed clear improvements in cognitive function, Fotuhi said.

He cautioned, however, that these gains were modest and did not represent a return to normal cognition. The observed changes were on the ADAS-Cog, which ranges from 0 to 80 points. Lifestyle interventions improved cognitive function from 1.3 to 2.6 points on the ADAS-Cog.

By contrast, in the MABs trials, cognitive scores declined in all groups, although the decline was slower among treated patients. MABs reduced cognitive decline by approximately 1.4-1.5 points compared with control participants.

When the results were analyzed as percentage differences vs controls, lifestyle interventions showed substantially greater relative benefits — up to nearly 11-fold higher, Fotuhi said.

In the MAB trials, the percentage difference between intervention and control groups was smaller, suggesting that reductions in amyloid do not necessarily translate into meaningful cognitive benefits, Fotuhi said.

While amyloid plaques and tau tangles are key features of AD, they represent only part of the underlying pathology, Fotuhi noted.

“More than 90% of patients who are diagnosed with Alzheimer’s disease have multiple pathologies in their brain. There’s evidence of increased inflammation, reduced blood flow, and impairment in the lymphatic waste management system in the brain,” he said.

Fotuhi plans to continue this line of research to determine, for example, whether exercise alone can improve cognitive function and reduce brain pathology. He also emphasized the need for objective measures — such as exercise endurance and detailed assessments of sleep and diet — to better define how much of an individual lifestyle intervention is needed to maintain cognition.

“We need to tease out the details so instead of just giving some broad recommendations, we can give very specific recommendations,” he said.

Experts Weigh In

Neelum Agarwal, MD, professor, Department of Neurological Sciences, Rush University in Chicago, a discussant at the session where the research was presented, cautioned against directly comparing the two approaches.

She noted that MABs target a specific pathology — “and do so pretty well” — whereas lifestyle approaches are inherently multimodal.

Agarwal also noted that MABs are associated with a monitoring burden and potential safety concerns, particularly the risk for amyloid-related imaging abnormalities (ARIA). 

“We’re going to learn more and more about ARIA as we administer these drugs to more people and understand the implications of that,” said Agarwal.

She also noted that not all patients are eligible to receive MABs.

In contrast, lifestyle interventions typically follow a multidomain approach, targeting factors such as diet, physical activity, cognition, and sleep, and offering scalable strategies that can reach a broad and diverse population, Agarwal said.

She added that these interventions provide benefits beyond cognition, including improvements in physical functioning and vascular health.

Agarwal said, an integrated approach that combines lifestyle strategies with medication is likely optimal, pointing to cardiology as a field that has long used such models. Ultimately, she emphasized, patients benefit from a comprehensive brain health plan that is continuously evaluated and optimized over the course of care.

Echoing Agarwal, Chadwick Hales, MD, PhD, associate professor of neurology at Emory University School of Medicine, Atlanta, and moderator of the session, agreed that multiple approaches will likely be needed to manage AD and that the benefit of each intervention may vary across patients.

For patients who are not yet symptomatic, lifestyle modifications remain important for reducing the risk for dementia later in life, he said. Hales noted that the 2024 Lancet Commission estimated that up to 45% of dementia risk factors are modifiable.

Fotuhi, Agarwal, and Hales reported having no relevant conflicts of interest.