World Brain Day: Emerging Ways to Prevent Neurologic Conditions

Ahead of World Brain Day on July 22, NeurologyLive examines a shift taking hold across the field: prevention. For decades, neurologic care has centered on managing disease after diagnosis. New research is pushing the conversation earlier, toward reducing risk before symptoms appear. 

From established risk factor frameworks to repurposed metabolic drugs, sleep science, the gut brain axis, and wearable technology, investigators are testing whether neurologic disease can be delayed, or avoided altogether. Below, we break down 5 emerging strategies shaping this next chapter of preventive neurology, and what the evidence says so far.

Multidomain Modifiable-Risk-Factor Reduction

Across the life course, an estimated 45% of dementia cases worldwide are attributable to 14 potentially modifiable risk factors, according to the 2024 update from the Lancet Standing Commission on dementia prevention, intervention, and care.¹ These factors, including obesity, smoking, excessive alcohol use, physical inactivity, diabetes, and more, cluster across early-, mid-, and late-life windows rather than concentrating near disease onset. For clinicians, this life-course framing reinforces that dementia risk reduction is a cumulative, decades-long undertaking rather than a late-stage intervention.

The strongest randomized evidence for translating this risk-factor framework into practice comes from the FINGER study, which randomly assigned 1259 at-risk older adults to a 2-year multidomain intervention.² The intervention group showed a small but statistically significant relative benefit in a composite neuropsychological test battery z score compared with controls (between-group difference in annual change, 0.022; 95% CI, 0.002-0.042; P =.03), Findings from the study suggest that multidomain, lifestyle‐based interventions lasting for 2 years can have beneficial effects on lifestyles and cognition in older at-risk patients.

That structure-and-intensity relationship was reinforced by the US POINTER trial (NCT03688126), which randomly assigned 2111 at-risk adults aged 60 to 79 years to a structured, higher-intensity multidomain lifestyle intervention or to a self-guided version.³ Both groups improved on a global cognitive composite over 2 years, but the structured group showed a significantly greater annual rate of improvement than the self-guided group (difference, 0.029 SD/y; 95% CI, 0.008-0.050; P =.008), with benefit consistent regardless of APOE ε4 carrier status. This suggests that a structured, higher-intensity intervention had greater benefits on global cognition compared with an unstructured, self-guided intervention in older adults at risk of cognitive decline and dementia.

Metabolic-Pathway Drugs as Neuroprotective Agents

One of the most closely watched developments in preventive neurology has been the repurposing of GLP-1 receptor agonists (GLP-1RAs), drugs developed for type 2 diabetes and obesity, as potential disease-modifying agents for neurodegenerative conditions. GLP-1 is an incretin hormone that has emerged as a promising neuroprotective agent for disorders including Alzheimer disease (AD), Parkinson disease (PD), and stroke, conditions marked by progressive neuronal dysfunction with treatments that remain largely symptomatic.⁴ Preclinical studies have shown GLP-1RAs can reduce neuroinflammation, oxidative stress, and pathological protein aggregation, while enhancing glucose metabolism and mitochondrial function.⁵

The strategy gained relevance because it connects two established evidence bases: the drugs' well-characterized use in metabolic disease, and growing recognition of metabolic dysfunction as a driver of neurodegeneration. GLP-1 receptors are present within the central nervous system, where signaling influences synaptic plasticity, neuroinflammation, and cellular energy management pathways implicated in dementia and Parkinson disease.⁶

Clinical evidence has been mixed. In Parkinson disease, agents such as exenatide and lixisenatide have shown motor benefits. In Alzheimer disease, the largest test to date came from the phase 3 EVOKE and EVOKE plus trials of oral semaglutide, which did not meet their primary endpoint. Results did not support the efficacy of semaglutide in slowing clinical progression in participants with early Alzheimer disease, despite improvement in disease-related biomarkers.⁷

Sleep and Glymphatic Clearance as a Preventive Target

A parallel line of preventive science treats sleep itself as a modifiable biological process rather than a lifestyle habit. The glymphatic system was shown in mouse models to be substantially more active during sleep than wakefulness, with the interstitial space expanding by roughly 60% and β-amyloid clearance nearly doubling during sleep or anesthesia compared with the awake state.⁸ Because this convective flow appears to depend heavily on slow-wave, non-REM sleep, sleep architecture may prove relevant to clearance efficiency, though this remains largely a preclinical finding awaiting fuller validation.

Translational evidence in humans is consistent with a glymphatic link to Alzheimer disease (AD) pathology, though it remains indirect. Imaging studies showed that clearance of amyloid and tau PET tracers from cerebrospinal fluid (CSF) is measurably reduced in patients with AD compared with cognitively healthy controls, and altered aquaporin-4 expression has been observed in AD brain tissue. These findings are consistent with, but not proof of, impaired glymphatic function contributing to pathology accumulation.⁹ Imaging using intrathecal contrast in humans has also demonstrated CSF flow patterns that resemble the rodent glymphatic pathway, supporting its relevance beyond animal models.

Additional acute human data reinforce the sleep-amyloid relationship directly. For example, in a positron emission tomography (PET) study using the tracer 18F-florbetaben, a single night of total sleep deprivation produced a significant increase in β-amyloid burden in the right hippocampus and thalamus relative to a rested baseline. Separately, habitually shorter self-reported sleep duration correlated with higher baseline amyloid burden across several subcortical regions.¹⁰ These findings position sleep quality and duration as a plausible, low-risk target for dementia risk-reduction counseling.

The Gut-Brain Axis and Dietary/Microbiome Interventions

The gut-brain axis has moved from a niche research interest to a mainstream target in preventive neurology. The microbiota-gut-brain axis is increasingly recognized as a critical regulator of brain health, with disruptions implicated in AD, PD, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and stroke, including post-stroke cognitive impairment.¹¹

Interest in this strategy is growing partly because gut changes appear to precede clinical symptoms, raising the possibility of intervention during a prodromal window. A study published in April 2026 found that analysis of gut microbes can reveal elevated PD risk before a person develops any symptoms.¹² That finding built on earlier work showing gut microbiota composition is altered even in early disease stages and correlates with clinical symptoms as PD progresses.¹³

On the intervention side, diet remains the most studied lever. Diet is one of the most important environmental factors shaping gut microbiota structure and function, and manipulating the microbiota through specific dietary patterns may represent a promising approach for preventing neurodegenerative disease.¹⁴ Beyond diet, microbiome-based interventions using probiotics, prebiotics, synbiotics, and postbiotics can modulate the axis and may help reduce risk of neurological changes associated with neurodegenerative disease.¹⁵ Small randomized trials are already testing this directly. A 2025 trial in patients with PD found improvements in constipation, motor symptom scores, and quality of life scores among participants receiving probiotics and nicotinic acid compared with placebo.¹⁶

Digital Biomarkers and Wearables for Earlier, Personalized Prevention

Continuous, real-world monitoring is reshaping how clinicians identify neurologic risk before an acute event occurs. Rapid advances in digital health, wearable biosensors, and artificial intelligence have transformed consumer smartwatches into potential clinical tools capable of continuous rhythm surveillance, with improved detection of atrial fibrillation recurrence and burden compared with traditional monitoring.¹⁷

Atrial fibrillation is particularly attractive for early detection since it is often asymptomatic and stroke prevention strategies are already well established.¹⁸ A randomized controlled trial published in late 2025 tested this directly, evaluating new onset atrial fibrillation detection using remote smartwatch-based screening in patients at elevated stroke risk.¹⁹

Blood-based biomarkers are also emerging as a more accessible screening tool for cerebral small vessel disease, a major driver of stroke and vascular dementia that has traditionally required neuroimaging to detect. This has prompted a recent proliferation of blood-based biomarker studies aimed at developing accessible tools for early detection and risk stratification. Among candidate markers, glial fibrillary acidic protein has been linked to disease severity and is being investigated as an early screening marker.²⁰

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