From childhood stress and pollution to sleep, inflammation, and the gut microbiome, AHA’s new framework shows why protecting your brain health must start long before old age.
Research: Brain Health Across the Lifespan: A Framework for Future Research: American Heart Association Scientific Statement. Image credit: Anton Vierietin / Shutterstock
A recent scientific statement from the American Heart Association was published in a journal. strokeresearcher overview Rationale for extending brain health beyond vascular risk factors to a holistic, lifelong framework. The latest framework emphasizes optimal cognitive, emotional, and behavioral functioning throughout the life course.
This comprehensive scientific statement highlights that identifying modifiable vascular and non-vascular contributors to brain health, cognitive decline, and neurodegeneration is a clinical priority as the world’s adult population aged 65 and older is expected to exceed 2 billion by 2050.
We then synthesize current evidence on chronic inflammation, environmental toxicants, mental health disorders, and socio-economic status (SES), as well as address sleep, dysbiosis, childhood infections, and chronic medical conditions, discuss their potential roles in shaping brain health and resilience, and identify strategies to reduce their impact and enhance neuroresiliency.
Lifespan Brain Health Background
Research on brain health and cognitive resilience (usually defined as the brain’s ability to recover after an injury) is considered to be increasingly important as records highlight that global aging is increasing the prevalence of mental illness, illicit drug use, neurological disorders and cognitive decline in later life.
Previous paradigms in the field focused on “neurovascular” targeting stroke prevention through the management of hypertension and diabetes and vascular dementia, but new research shows that vascular factors typically do not emerge as major contributors to overt stroke until young adulthood.
As a result, the American Heart Association (AHA) 2021 Agenda identified modifiable risk factors but documented the urgent need for a more detailed understanding of non-vascular contributions.
AHA Brain Health Statement Scope
This 2026 AHA Scientific Statement builds on the AHA’s early brain health challenges by exploring how early childhood exposures experienced during brain maturation can prime older adults for central nervous system (CNS) neurodegeneration and cognitive decline.
This scientific statement is a comprehensive synthesis of years of interdisciplinary research bridging neurology, psychiatry, and geriatrics. Rather than reporting a single new analytical dataset, we review evidence from multiple scientific literature, including:
• Large longitudinal cohorts: To assess the effects of prenatal air pollution on psychomotor development, data from six European population-based birth cohorts (n = 9,482 children) were examined.
• Neuroimaging and molecular studies: Human neuroimaging and postmortem studies have provided data on intracellular signaling, gene expression, and neural atrophy in the medial prefrontal cortex (mPFC) and hippocampus.
• Clinical meta-analysis: Evaluation of hazard ratios associated with air pollutants and dementia risk across 14 different studies.
The statement also discusses evidence across preclinical, epidemiological, clinical, and mechanistic studies, including brain-derived neurotrophic factor (BDNF) expression, beta-amyloid and tau pathology, gray matter volume, and functional integrity of the blood-brain barrier.
Non-vascular brain health risk factors
This scientific statement identified several modifiable areas 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 microbiota and systemic inflammation, 5. Reduced sleep quality, and 6. Early childhood infections and chronic medical conditions.
Chronic exposure to PM2.5 (particulate matter with a diameter of 2.5 μm or less) is now considered to be an important environmental factor associated with the risk of dementia. These results come from a meta-analysis that reported an overall hazard ratio of 1.04 (95% confidence interval, 0.99 to 1.09) per 2 μg/m3 of PM2.5.
Additionally, prenatal NO2 (nitrogen dioxide) exposure was shown to be associated with a 0.68 point decrease (95% confidence interval, -1.25 to -0.11) per 10 μg/m3 increase in global psychomotor development score. In particular, approximately 26% of ischemic stroke injuries in adults are associated with air pollution.
Current data link depression and anxiety to biological pathways that may accelerate biological aging. Depressive symptoms in early life were found to be associated with a more than two-fold increase in dementia risk.
Biological mechanisms driving this process may involve chronic stress, which induces a sustained reduction in BDNF signaling and promotes synaptic loss, particularly in the mPFC and hippocampus. Unfortunately, remission rates with current monotherapy for these diseases remain low at 30% to 50%.
Adverse childhood experiences (ACEs) are now considered a common condition, with 17.3% of U.S. adults reporting four or more ACEs. Research has shown that these experiences can trigger a “toxic stress response,” leading to prolonged activation and allostatic overload of the hypothalamic-pituitary-adrenal (HPA) axis.
Finally, imbalances in the gut-brain axis are 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 highlights that a high-fiber diet supports the production of short-chain fatty acids (SCFAs), modulates blood-brain barrier integrity and microglial activation, supports microbial diversity, reduces inflammation, and may promote metabolic health in the brain and heart.
Poor sleep quality has also been highlighted as a life course influence on brain health. Sleep supports brain maturation, memory consolidation, synaptic regulation, and glymphocyte clearance of proteins, but insufficient sleep and obstructive sleep apnea are associated with cognitive decline, risk of dementia, beta-amyloid and tau accumulation, and changes in cerebral blood flow.
The statement further notes that early childhood infections and chronic medical conditions in children, such as congenital heart disease, sickle cell anemia, moyamo, obesity, and risk of infection-related stroke, can impact brain development, cognition, and mental health through vascular, inflammatory, metabolic, and psychosocial pathways.
Comprehensive brain health prevention strategy
The statement concludes that brain health needs to be managed through a holistic, lifelong approach that prioritizes early detection and individualized intervention. The AHA calls for strategies at the individual, clinical, public health, and policy levels that include regular physical activity, sleep hygiene to promote beta-amyloid removal from glymphatics, and a polyphenol-rich diet and Mediterranean-style diet to reduce systemic inflammation.
Future research should focus on personalized, culturally responsive practices and identification of CNS-specific biomarkers to extend cognitive lifespan for all communities.
