From childhood stress and pollution to sleep, inflammation, and the gut microbiome, the AHA’s new framework shows why protecting brain health must begin long before old age.
Study: Brain Health Across the Life Span: A Framework for Future Studies: A Scientific Statement From the American Heart Association. Image Credit: Anton Vierietin / Shutterstock
In a recent American Heart Association scientific statement published in the journal Stroke, researchers outline the rationale for expanding brain health beyond vascular risk factors to a holistic, lifelong framework. The modernized framework emphasizes optimal cognitive, emotional, and behavioral functioning throughout the life course.
The comprehensive scientific statement highlights that, with the global population of adults aged 65 and older expected to exceed 2 billion by 2050, identifying modifiable vascular and nonvascular contributors to brain health, cognitive decline, and neurodegeneration is a clinical priority.
It subsequently synthesizes current evidence on chronic inflammation, environmental toxicants, mental health disorders, and socioeconomic status (SES), while also addressing sleep, gut microbiome dysbiosis, early-life infection, and chronic medical conditions, describing their potential roles in shaping brain health and resilience and identifying strategies to mitigate their effects and enhance neural resilience.
Life Span Brain Health Background
Research on brain health and cognitive resilience, typically defined as the capacity for the brain to recover following an insult, is thought to be increasingly critical as records emphasize that global aging is driving the prevalence of late-life mental illness, illicit substance use, neurologic disorders, and cognitive decline.
While previous paradigms in the field focused heavily on the "neurovasculome," targeting stroke prevention and vascular dementia via the management of hypertension and diabetes, emergent research indicates that vascular factors do not typically emerge as primary drivers of overt stroke until young adulthood.
Consequently, the American Heart Association (AHA) 's 2021 agenda identified modifiable risk factors but documented that a more granular understanding of nonvascular contributions was urgently needed.
AHA Brain Health Statement Scope
This 2026 AHA scientific statement builds on the AHA's earlier brain health agenda by exploring how early-life exposures experienced during brain maturation can prime the central nervous system (CNS) for neurodegeneration and cognitive decline in older adults.
This scientific statement is a comprehensive synthesis of years of transdisciplinary research that bridges neurology, psychiatry, and geroscience. Rather than reporting a single new analytical dataset, it reviews evidence from multiple scientific literatures, including:
• Large-scale longitudinal cohorts: Data from 6 European population-based birth cohorts (n = 9,482 children) were reviewed to assess the impact of prenatal air pollution on psychomotor development.
• Neuroimaging and molecular studies: Human neuroimaging and postmortem studies provided data on intracellular signaling, gene expression, and neuronal atrophy in the medial prefrontal cortex (mPFC) and hippocampus.
• Clinical meta-analyses: Evaluation of hazard ratios associated with ambient air pollutants and dementia risk across 14 distinct studies.
The statement also discusses evidence across preclinical, epidemiologic, clinical, and mechanistic studies, including brain-derived neurotrophic factor (BDNF) expression, beta-amyloid and tau pathology, gray matter volume, and the functional integrity of the blood-brain barrier.
Nonvascular Brain Health Risk Factors
The scientific statement identified several modifiable domains with varying strengths of supporting evidence that exert significant pressure on brain homeostasis: 1. Environmental toxicants, 2. Stress, depression, and anxiety, 3. Social determinants and toxic stress, 4. Gut microbiome and systemic inflammation, 5. Poor sleep quality, and 6. Early-life infection and chronic medical conditions.
Chronic exposure to PM2.5 (particulate matter with a diameter ≤ 2.5 µm) is now considered an important environmental factor associated with dementia risk. These findings draw from meta-analyses, which reported an overall hazard ratio per 2 µg/m3 of PM2.5 at 1.04 (95% confidence interval, 0.99–1.09).
Furthermore, prenatal NO2 (nitrogen dioxide) exposure was shown to be associated with a decrease of 0.68 points (95% confidence interval, −1.25 to −0.11) in global psychomotor development scores per 10 µg/m3 increase. Notably, approximately 26% of disability associated with ischemic stroke in adults is linked to air pollution.
The present data link depression and anxiety with biological pathways that may accelerate biological aging. Early-life depressive symptoms were found to correlate with a 2-fold or greater increase in dementia risk.
The biological mechanism driving this process may involve chronic stress, which induces sustained decreases in BDNF signaling, fostering synaptic loss, particularly in the mPFC and hippocampus. Unfortunately, current single-modality treatment remission rates for these conditions remain modest, ranging from 30% to 50%.
Adverse childhood experiences (ACEs) are now considered a prevalent condition, with 17.3% of US adults reporting ≥ 4 ACEs. Studies have shown that these experiences can trigger a "toxic stress response," leading to prolonged activation of the hypothalamic-pituitary-adrenal (HPA) axis and allostatic overload.
Finally, dysbiosis of the gut-brain axis has been associated with Alzheimer's disease (AD) and Parkinson's disease (PD), with evidence suggesting bidirectional gut-brain involvement rather than a fully established causal relationship in humans. The AHA emphasizes that high-fiber diets support the production of short-chain fatty acids (SCFAs), which modulate blood-brain barrier integrity and microglial activation and may support microbial diversity, reduce inflammation, and promote brain and cardiometabolic health.
Poor sleep quality was also highlighted as a life-course influence on brain health. Sleep supports brain maturation, memory consolidation, synaptic regulation, and glymphatic clearance of proteins, while inadequate sleep and obstructive sleep apnea are associated with cognitive decline, dementia risk, beta-amyloid and tau accumulation, and altered cerebral blood flow.
The statement further notes that early-life infections and chronic pediatric medical conditions, including congenital heart disease, sickle cell anemia, moyamoya, obesity, and infection-related stroke risks, can influence brain development, cognition, and mental health through vascular, inflammatory, metabolic, and psychosocial pathways.
Holistic Brain Health Prevention Strategies
The statement concludes that brain health must be managed through a holistic, life span approach that prioritizes early detection and personalized intervention. The AHA calls for individual, clinical, public health, and policy-level strategies, including regular physical activity, sleep hygiene to facilitate glymphatic clearance of beta-amyloid, and a polyphenol-rich or Mediterranean-style diet to reduce systemic inflammation.
Future research must focus on personalized, culturally responsive practices and the identification of CNS-specific biomarkers to extend cognitive longevity across all communities.
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