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From vaccines that may lower dementia risk to new transfusion strategies after brain injury and definitive proof that lifestyle change protects cognition, 2025 delivered several landmark neurology studies. Highlighted in JAMA’s inaugural Research of the Year roundup, these findings are already reshaping clinical practice and public health conversations worldwide.
A Year That Changed the Neurology Conversation
In its first-ever Research of the Year selection, JAMA spotlighted studies published between October 2024 and September 2025 that editors believe will have lasting impact on medicine. Among them were three neurology-focused investigations that stood out for their rigorous methods, real-world relevance, and potential to improve outcomes across the lifespan.
Together, these studies tackled long-standing questions: Can a common vaccine protect the brain? How much blood is enough after a brain injury? And can lifestyle change truly slow cognitive aging in diverse populations?
The answers, while nuanced, are already influencing how clinicians counsel patients and how health systems think about brain health.
A Shingles Vaccine and Dementia Risk: A Natural Experiment With Big Implications
The idea that a shingles vaccine could reduce dementia risk has circulated for years, but skeptics raised a legitimate concern: healthy vaccine bias. People who get vaccinated tend to be healthier overall, making it hard to know whether observed benefits come from the vaccine or from underlying lifestyle differences.
Pascal Geldsetzer, MD, PhD, MPH, an assistant professor of medicine at Stanford Medicine, and colleagues found a way around that problem using a rare natural experiment in Australia.
When Australia launched its national shingles vaccination program in 2016, eligibility was sharply defined by birth date. Only people aged 70–79 on November 1, 2016, qualified for the free live attenuated vaccine (Zostavax). Those just days older were excluded; those days younger were included.
“People born days apart are essentially identical in terms of health behaviors, genetics, and risk factors,” Geldsetzer explained. “The only meaningful difference was vaccine eligibility.”
What the Data Showed
Analyzing primary care records from more than 101,000 patients across 65 general practices, the researchers followed participants for a median of 7.4 years. Eligibility for the shingles vaccine was associated with a 1.8 percentage point absolute reduction in new dementia diagnoses (P = .01).
In relative terms, that translated into roughly a 20% reduction in dementia incidence over seven years—an effect Geldsetzer described as “large.”
Crucially, these findings replicated results from a Welsh cohort published weeks earlier in Nature, strengthening confidence that the association reflects a causal relationship rather than chance or bias.
Mary McDermott, MD, deputy editor of JAMA, called the study “timely and topical,” noting its innovative design and public health relevance.
Why Might a Shingles Vaccine Affect the Brain?
Several biologically plausible mechanisms exist. The varicella-zoster virus, which causes chickenpox and shingles, remains dormant in the nervous system for life and can trigger chronic inflammation. Growing evidence links neuroinflammation to dementia development.
Live attenuated vaccines may also have broader immune-modulating effects beyond their target infection. “We don’t yet know which mechanism is at play, or to what degree,” Geldsetzer said, “but the consistency across countries and healthcare systems makes the signal hard to ignore.”
Limitations and the Funding Gap
Despite compelling evidence, definitive proof would require a randomized clinical trial. That presents a challenge: Zostavax is off patent, giving pharmaceutical companies little incentive to fund large trials.
“We’re hoping for support from philanthropy and private foundations,” Geldsetzer said.
For now, clinicians are already taking note. The shingles vaccine is safe, inexpensive, and one-time, and many physicians report more proactive discussions with patients about its potential brain health benefits.
After Brain Injury, When to Transfuse? The TRAIN Trial Provides an Answer
Few questions in neurocritical care have been as persistent as how low is too low for hemoglobin levels after acute brain injury.
While restrictive transfusion strategies are standard in general intensive care units, the injured brain’s high oxygen demands raised concerns that anemia could worsen neurologic outcomes.
The TRAIN trial, published in JAMA, directly addressed this uncertainty.
A Global Randomized Trial
Investigators enrolled 850 patients with traumatic brain injury, subarachnoid hemorrhage, or intracerebral hemorrhage across 72 ICUs in 22 countries. Participants were randomized to receive transfusions at either:
- A liberal threshold (hemoglobin < 9 g/dL), or
- A restrictive threshold (hemoglobin < 7 g/dL).
At 180 days, outcomes clearly favored the liberal strategy. Unfavorable neurologic outcomes occurred in 62.6% of the liberal group versus 72.6% of the restrictive group (adjusted relative risk, 0.86; P = .002). Functional independence was achieved by 37% versus 27%, respectively.
“My jaw dropped,” said coauthor Kirsten Møller, MD, PhD, of Copenhagen University Hospital. “I never expected such a clear difference.”
Why This Study Matters
Unlike earlier trials, TRAIN used a stringent definition of good outcome, counting only patients who regained functional independence. Survival rates were similar between groups; the benefit came from better neurologic recovery among survivors.
Philip Greenland, MD, senior editor at JAMA, wrote that TRAIN may “actually change practice,” noting that prior guidance relied heavily on extrapolation.
Practical Considerations and Caveats
The liberal strategy typically required just one additional unit of blood per patient. It also appeared to reduce cerebral ischemic events, though detection methods varied by center.
Implementation is already underway in parts of Europe, though resource limitations—particularly blood supply—remain a barrier in some regions.
For clinicians, the takeaway is straightforward: avoid anemia in the early days after brain injury, as maintaining hemoglobin near 9 g/dL can meaningfully improve long-term outcomes.
Lifestyle Change and Cognition: Proof It Works in the U.S.
Lifestyle interventions have long been promoted for brain health, but critics questioned whether results from Finland’s landmark FINGER trial would translate to more diverse populations.
The U.S. POINTER study answered that question.
Inside the Trial
The 2-year randomized trial enrolled 2,111 adults aged 60–79 years across five U.S. sites. Participants were sedentary, had suboptimal diets, and were at increased risk for cognitive decline.
They were assigned to either a structured multidomain intervention—including diet, exercise, cognitive training, and vascular risk monitoring—or a self-guided approach.
Both groups improved, but the structured program produced a statistically significant greater benefit, with cognitive scores improving by 0.029 standard deviations per year more than the control group (P = .008).
Why the Effect Size Matters
Laura D. Baker, PhD, lead investigator and professor at Wake Forest University School of Medicine, emphasized that this difference translates into slowing cognitive aging by 1–2 years.
“If I get one more year of being sharp, I’ll take it,” participants told her.
Beyond cognition, participants improved cardiovascular health and, in some cases, reduced medications for blood pressure and cholesterol.
Addressing Criticisms
Some critics argued the intervention was too intensive. Baker disagreed. “You can’t have enduring change without changing habits,” she said, noting that social connection and accountability were among participants’ favorite aspects.
JAMA editors highlighted the trial’s diverse enrollment and strong retention, calling it a milestone for implementation in real-world settings.
What This Means for Public Health
Taken together, these studies reinforce a broader message: brain health is modifiable.
- Vaccination strategies may offer unexpected protection against neurodegenerative disease.
- Simple changes in ICU protocols can improve recovery after devastating injuries.
- Lifestyle interventions, when structured and supported, can slow cognitive aging even in high-risk groups.
As these findings move from journals into clinics and communities, they underscore the value of rigorous, well-designed research in shaping healthier futures.
Medical Disclaimer
This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.
References
- https://www.medscape.com/viewarticle/jamas-top-neurology-studies-2025-key-insights-years-most-2026a10002ua
