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Cardiorespiratory exercise after ischemic stroke had benefits on cognition but not brain volume in a randomized controlled study conducted in Australia.

In the PISCES-ZODIAC trial, an 8-week cardiorespiratory exercise intervention started 2 months following ischemic stroke did not preserve hippocampal volume more than an active control of balance and stretching exercises.

However, there was “promising evidence” of better executive and global cognitive performance at 12 months after stroke with cardiorespiratory exercise, the researchers reported.

The study, with first author Amy Brodtmann, PhD, with Monash University Central Clinical School, Melbourne, Australia, was published online on August 26 in JAMA Network Open.

Improving Brain Health After Stroke

Stroke survivors face a heightened risk for cognitive impairment and dementia, with hippocampal atrophy being a strong predictor of decline.

Brodtmann and colleagues tested whether an intense structured cardiorespiratory exercise program could preserve hippocampal volume (primary outcome) and cognition (secondary outcome) when initiated during the subacute period.

They enrolled 107 adult survivors of ischemic stroke with premorbid modified Rankin scores ≤ 3, who were able to exercise 2 months after their stroke.

All participants completed three 60-minute sessions per week for 8 weeks. In the intervention group, this consisted of prescribed aerobic and resistance training that progressed in intensity. The control group received balance and stretching training.

Brain MRI and neurocognitive testing were performed at 2, 4, and 12 months after stroke.

The cardiorespiratory exercise intervention had no significant impact on hippocampal volume. Between 2 and 4 months, hippocampal volume declined 0.26% in the intervention group and 0.11% in the control group (adjusted mean difference in relative change, -0.10%; P = .83).

However, notable benefits emerged in cognitive domains commonly affected in stroke survivors.

Patients in the cardiorespiratory exercise group demonstrated better performance on executive function, measured by the Trail Making Test, part B, at 12 months (adjusted mean difference, -3.75 seconds), as well as global cognition, including memory, language, and praxis, as assessed by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (adjusted mean difference, -1.00).

Both interventions were safe with no serious adverse events.

Brodtmann and colleagues said there are several possible explanations for the neutral finding on hippocampal volume. One is the choice of an active balance and stretching control as the comparator, which may have obscured any potential effects of cardiorespiratory exercise on brain volume.

“The comparable atrophy rates suggest that our active control was equivalent for brain volume preservation, consistent with increasing evidence that balance training has brain benefits,” the researchers wrote.

And in their view, the observation that cardiorespiratory exercise may lead to better cognitive outcomes at 12 months is “novel and of great importance to the stroke community.” “Exercise therapists could aim for cardiorespiratory interventions, encouraged by improved cognitive outcomes, but be reassured that balance and stretching interventions offer comparable brain volume effects,” they concluded.

Far From a Negative Trial

Writing in a linked editorial, Zafer Keser, MD, vascular neurologist with Mayo Clinic, Rochester, Minnesota, said, at first glance, the lack of significant change in the primary imaging outcome — hippocampal volume — might suggest a “negative” trial. However, from a clinical standpoint, the findings are both “positive and actionable,” he noted.

“The study demonstrated that aerobic exercise confers tangible clinical benefits, reinforcing the idea that it should be regarded not just as a tool for improving mobility and cardiovascular health but also as a potentially viable intervention for cognitive recovery after stroke,” Keser wrote.

“This trial marks a pivotal step toward embedding personalized, intensity-guided exercise programs into the core of poststroke care,” Keser said.

He cautioned, however, that the study cohort reflected a population with relatively mild strokes and higher functional capacity, which likely contributed to their ability to adhere to the demanding exercise protocol.

“Future trials should aim to include more representative stroke populations, including individuals with moderate-to-severe strokes, those with significant cardiovascular risk, and patients with hemorrhagic strokes. Expanding the scope of study populations will be critical for informing clinical guidelines and ensuring equitable access to evidence-based poststroke interventions,” Keser said.

The study disclosed having no commercial funding. Brodtmann and Keser reported having no relevant disclosures.