2026 AHA科学声明：整个生命周期的大脑健康—未来研究框架

Figure 2. Recommendations to optimize brain health.

ACE indicates adverse childhood experience; GLP-1, glucagon-like peptide-1; HEPA, high-efficiency particulate air; and SCFA, short-chain fatty acid.

cardiovascular or stroke-related morbidity and mortality.$^{14}$ Comorbid depression can worsen the outcomes of medical conditions and neurocognitive disorders and contribute to higher mortality rates, including from suicide.$^{15}$ The literature suggests an association between

depression and dementia, and growing evidence implies that timing of depression may be important to defining this association. For example, depression or depressive symptoms earlier in life are associated with a 2-fold or greater increase in risk of dementia,$^{10}$ and the role of

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other psychiatric and substance use disorders in cognitive decline and dementia has been well-established.$^{16}$ The critical period for addressing mental health concerns may begin far earlier than initially appreciated; data show reduced gray matter volume in children who have experienced depression.$^{17}$

The likely biologic mechanisms linking depression and dementia include vascular disease, alterations in glucocorticoid steroids, hippocampal atrophy, increased deposition of β-amyloid plaques, inflammatory changes, and deficits of nerve growth factors.$^{10}$ Preclinical models of anxiety and depression, as well as human neuroimaging studies, point to altered neuroplasticity as a driving factor—specifically neuronal atrophy and synaptic loss in the medial prefrontal cortex and hippocampus.$^{18}$ Studies of molecular and cellular mechanisms in rodent models and convergent neuroimaging and postmortem studies of individuals with depression reveal alterations at the levels of intracellular signaling, gene expression, neurotrophic factors, neurogenesis, neuroinflammation, excitatory and inhibitory neurotransmission, and synaptic number and function, which have been described in several brain regions implicated in depression.$^{18-23}$ One of the leading theories highlights the roles of the prefrontal cortex and hippocampus, including disruption of neurotrophic factors and synaptic connectivity related to neuroplasticity mechanisms, which can further contribute to neurodegenerative and vascular brain changes later in life.$^{24,25}$

In addition, chronic stress leads to sustained decreases in neuroprotective factors (eg, BDNF [brain-derived neurotrophic factor] expression and signaling) that damage or hinder plasticity, fostering neuronal atrophy and decreased synaptic number and function, particularly in the medial prefrontal cortex and hippocampus.$^{24}$ This results in maladaptation to the environment, compromising learning and stress coping, and to downstream gain of activity in some limbic network regions, such as the amygdala and lateral habenula, which is linked to anhedonia, anxiety, and chronic states of negative emotions. Chronic stress and negative emotions subsequently promote a proinflammatory state, contributing to neurodegenerative and cerebrovascular changes and accelerating biologic aging.$^{26-28}$ Excessive substance use (eg, tobacco, alcohol, illicit drugs) can directly damage brain cells and increase the risk of dementia through accelerated senescence, oxidative stress, altered neuroimmune function and metabolism, pathogenic tauopathy development and spread, and disruption of neuronal excitatory-inhibitory balance.$^{29}$

Depression and anxiety are the leading causes of disease-related disability worldwide and remain chronic relapsing conditions with no reliable cures.$^{30}$ Remission rates are low for a single treatment modality (30%-50%), and relapse rates are high.$^{30}$ Addressing mental health conditions will likely be a catalytic driver of behavior

change in physical health, and evidence supports both early primary and secondary intervention approaches. With depression and anxiety being increasingly common-partly due to the ongoing stress and uncertainty in our society—the current mental health crisis may serve as a powerful motivator for young people to adopt healthier behaviors and improve overall well-being. It is therefore imperative to develop accessible, effective treatments for depression and anxiety, as recommended by several recent guidelines from the American Heart Association, American Academy of Neurology, and World Health Organization.$^{11,31,32}$

POLLUTION AND ENVIRONMENTAL EXPOSURES

Mounting evidence indicates that environmental exposures, including air pollution, heavy metals, pesticides, and other toxicants, are also powerful determinants of brain health across the life span, with effects well beyond emotional and psychologic well-being. Epidemiologic studies consistently associate chronic exposure to particulate matter with a diameter of <2.5 µm (PM2.5), a common air pollutant, with increased risk of mild cognitive impairment and AD, potentially mediated by neuroinflammation, oxidative stress, blood-brain barrier dysfunction, vascular changes, and accumulation of amyloid and tau pathology.$^{33.34}$ A recent meta-analysis investigating the role of air pollutants in risk of dementia reported that the overall hazard ratio per 2 µg/m$^{3}$ PM2.5 was 1.04 (95% CI, 0.99-1.09; 14 studies).$^{35}$ The overall hazard ratio per 10 µg/m$^{3}$ NO₂ was 1.02 (95% CI, 0.98-1.06; 9 studies) and that per 10 µg/m$^{3}$ NOx was 1.05 (95% CI, 0.98-1.13; 5 studies).$^{35}$ After consideration of all sources (eg, agriculture, road traffic, burning coal for energy, wildfires), PM2.5 from agriculture and wildfires appears specifically associated with an increased risk of dementia.$^{36}$

Beyond cognitive aging, prenatal and early-life exposures to pollutants may disrupt brain development, influencing neurobehavioral trajectories and cognitive outcomes. Maternal exposure to particulate matter is associated with adverse birth outcomes and effects on multiple systems, including brain development. An analysis of data from 6 European population-based birth cohorts that recruited mother-infant pairs from 1997 through 2008 (n=9482 children) found that air pollution exposure during pregnancy, particularly $NO_2$ (for which motorized traffic is a major source), was associated with reduced psychomotor development: the global psychomotor development score decreased by 0.68 points (95% CI, -1.25 to -0.11) per 10 µg/m$^{3}$ increase in $NO_{2}$.$^{37}$ Prenatal exposure to polycyclic aromatic hydrocarbons and heavy metals, such as lead or mercury, is also linked to lower IQ scores and increased risk of neurodevelopmental delay and disorder.$^{38}$

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Environmental neurotoxicants also intersect with neurodegenerative processes. Data indicate that air pollutants may accelerate neurodegeneration through microbial activation, systemic inflammation, and direct neuronal toxicity.$^{39}$ Studies have documented elevated markers of neuroinflammation and Alzheimer pathology in residents of highly polluted urban regions, even among children and young adults, suggesting that environmental exposures may prime the brain toward earlier neurodegenerative and vascular changes.$^{34,40}$ In addition, $\approx 26\%$ of disability associated with ischemic stroke in adults has been linked to air pollution, including ambient particulate matter (PM2.5) and household air pollution,$^{41}$ and studies examining the effects of adult and prenatal exposure to air pollution on mental health, brain structure, and function demonstrate regional (frontolimbic) associations with inflammation and oxidative stress, as well as alterations in neurotransmitters, neuromodulators, and their metabolites.$^{42}$ Pesticides and microplastics are also independently linked to neurodegenerative disorders through mechanisms such as oxidative stress, neuroinflammation, and disruption of the gut-brain axis.$^{43,44}$ Both pollutants can trigger accumulation of misfolded proteins, mitochondrial dysfunction, and damage to the blood-brain barrier, increasing risk and progression of neurologic diseases.

Environmental injustice exacerbates these risks, with people from underrepresented racial or ethnic groups facing disproportionate pollutant burdens and heightened vulnerability to neurotoxic effects.$^{45}$ Recognizing that people from underrepresented racial or ethnic groups and households with incomes below the poverty level experience disproportionate exposures, policies to reduce these environmental toxins should be prioritized. Addressing pollution as a modifiable risk factor represents a key opportunity to promote neurodevelopmental health, preserve cognitive function, and reduce dementia risk. Strategies to reduce exposure, including regulatory policies to lower emissions, urban planning to mitigate traffic-related pollution, and public health interventions, are needed to protect brain health across all life stages. Prevention of neurodegenerative and cerebrovascular disease should be a public health priority, particularly because exposure to pollution and environmental neurotoxicants is a modifiable risk factor.

CHRONIC INFLAMMATION

Chronic inflammation is also a central contributor to impaired brain health across the life span. Unlike acute, protective inflammation, chronic inflammation involves sustained immune activation that can drive long-term neurologic harm when resolution mechanisms fail. In early development, excessive or unresolved inflammation, often triggered by maternal infection or environmental insults, can disrupt key neurodevelopmental processes,

including synapse formation, myelination, and neuronal migration. This has been linked to increased risk for neurodevelopmental disorders, including autism spectrum disorder and schizophrenia.$^{46}$ During adolescence, chronic low-grade inflammation arising from early-life adversity, infection, psychosocial stress, or other environmental exposures can disrupt synaptic pruning and cortical remodeling, negatively affecting brain maturation and mental health. Emerging evidence suggests that elevated inflammatory markers during this stage are associated with increased vulnerability to mood disorders and cognitive deficits.$^{47}$ In adulthood, persistent inflammation may gradually erode neuronal integrity, even in the absence of overt disease. Within the central nervous system, prolonged microglial activation in a proinflammatory state results in the persistent release of mediators such as IL-1β (interleukin-1β), IL-6 (interleukin-6), and TNF (tumor necrosis factor).$^{48}$ These cytokines can disrupt synaptic plasticity, promote oxidative stress, and contribute to neuronal loss, as observed in neurodegenerative diseases like AD and Parkinson disease. The failure of specialized proresolving mediators (eg, resolvins) and efferocytosis (the cellular clearance of debris) appears to be key to this transition from beneficial to harmful neuroinflammation.$^{49}$

Chronic inflammation also has a complex, bidirectional relationship with cardiovascular and cerebrovascular health. Chronic inflammation damages blood vessels, accelerating atherosclerosis and endothelial dysfunction and increasing the risk of myocardial infarction, stroke, and impaired brain $circulation.^{50}$ Vascular injury itself promotes inflammation, creating a feed-forward loop that contributes to accelerated brain aging. Psychologic stress may further amplify chronic inflammation by dysregulating the hypothalamic-pituitary-adrenal axis and promoting sustained cortisol production. Prolonged cortisol exposure can alter hypothalamic-pituitary-adrenal axis feedback and induce glucocorticoid receptor resistance in immune cells, thereby diminishing the anti-inflammatory effects of cortisol and promoting a proinflammatory milieu.$^{51}$ This neuroendocrine immune crosstalk may perpetuate systemic inflammation, although individual responses vary considerably. Inflammatory pathways also accelerate brain aging by promoting cellular senescence and reducing neurogenesis. Elevated circulating inflammatory markers (eg, IL-6) are associated with hippocampal atrophy, reduced cognitive resilience, and accelerated decline in memory and executive function in aging populations.$^{52-54}$ Sex differences influence the consequences of inflammation. Women typically mount stronger immune responses than men, which can increase their susceptibility to neuroinflammatory conditions. In addition, declining estrogen levels during menopause may exacerbate inflammation-related cognitive decline in women.$^{55}$

Evidence-based mitigation strategies include regular physical activity, a Mediterranean-style diet, optimizing

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sleep, and reducing psychologic stress. These lifestyle approaches have shown consistent benefits, although optimal implementation protocols are under investigation.$^{5,56-60}$ By contrast, pharmacologic strategies often produce mixed results in human trials.$^{61}$ Despite strong efficacy in animal models, anti-inflammatory and antioxidant therapies have shown limited benefit in humans. This discrepancy likely reflects several challenges, including the greater heterogeneity of human populations due to comorbidities and lifestyle factors, as well as the relative insensitivity of clinical end points compared with those used in preclinical studies. Human trials are often underpowered, making it difficult to detect significant effects. Interventions in animal studies are also often initiated at precise timepoints early in disease progression; in humans, treatment begins after pathology is established, when damage may be less reversible. In addition, inflammation is not uniformly harmful, so broad suppression may disrupt necessary immune functions. Current clinical investigations include antioxidant therapies and metabolic modulators, such as glucagon-like peptide-1 receptor agonists, which have shown some promise in AD but require confirmatory studies.$^{62,63}$ Developing effective anti-inflammatory strategies requires a deeper understanding of resolution mechanisms, identification of improved central nervous system-specific biomarkers, and personalized approaches to individual inflammatory phenotypes and genetics.

GUT MICROBIOME DYSBIOSIS

The gut-brain axis is a bidirectional communication network between the gastrointestinal tract and the central nervous system, fundamentally influencing brain health and disease pathogenesis. The axis operates through neural, immune, and endocrine pathways, with its function profoundly influenced by the composition and metabolic activity of the gut microbiome. Emerging evidence suggests that alterations in gut microbiota can affect cognitive performance, emotion regulation, and susceptibility to neurodegenerative diseases.$^{64}$ Key microbial metabolites, notably short-chain fatty acids, directly modulate blood-brain barrier integrity, microglial activation, and neuroinflammatory signaling.$^{65,66}$ Fiber-rich diets support short-chain fatty acid production, whereas Western-style diets promote microbial dysbiosis, which correlates with increased intestinal permeability, systemic inflammation, and adverse cognitive outcomes. Environmental exposures such as air pollution and endocrine-disrupting chemicals can also disrupt the microbiome, thereby amplifying inflammation and oxidative stress, with subsequent neurodegenerative effects.$^{67,68}$ Sex-based differences in gut microbiota, potentially linked to estrogen's influence on reducing gut permeability and importance in hormone metabolism, may also contribute to sex-specific cognitive vulnerabilities.$^{69}$

The gut-brain axis exhibits distinct patterns of influence across various life stages, with a particular vulnerability during early development and aging. During the prenatal and early postnatal periods, establishment of the microbiome has a tremendous influence on neurodevelopment, with disruptions linked to neurodevelopmental disorders, including autism spectrum disorder. The heightened neuroplasticity of the developing brain makes it particularly susceptible to microbiome-mediated influences on neurogenesis, myelination, and synaptic development.$^{70,71}$ Adolescence represents another critical period, during which stress, inflammatory infections, poor diet, and antibiotic exposure can alter microbiota composition, potentially increasing neuroinflammation and future neurodegenerative risk. Changes to the adolescent brain, combined with hormonal changes, create unique vulnerabilities to microbiome disruptions, with potentially lasting consequences for mental health and cognitive function.$^{72}$ Infection, dysimmunity, and the gut microbiome are also implicated in the development of vascular malformations associated with childhood brain injury, including cerebral cavernous malformations.$^{73}$ In older populations, age-related shifts in microbiome composition are strongly correlated with the manifestations of neurodegenerative diseases. Aging reduces microbial diversity and increases gut barrier dysfunction and low-grade inflammation, potentially exacerbating neuroinflammatory processes.$^{74}$

AD shows particularly robust associations with gut dysbiosis, in which altered microbiota promote neuro-inflammation and cognitive decline through multiple pathways.$^{72,76}$ Parkinson disease similarly demonstrates gut-brain axis involvement, with microbiome changes potentially contributing to both motor and nonmotor symptoms.$^{68,72}$ The relationship between gut dysbiosis and these neurodegenerative conditions appears bidirectional, with disease progression further altering microbiome composition in a self-perpetuating cycle.

Modulating the gut microbiome presents a promising strategy for improving brain health. Interventions such as dietary modification, probiotic and prebiotic supplementation, and fecal microbiota transplantation aim to restore microbial balance and support cognitive function.$^{76,77}$ Recent trials (eg, PROMOTE [Protein and Skeletal Muscle in Older Twins: Role of the Gut Micro-biome]) show that prebiotics can modestly improve cognition in older adults,$^{78}$ and some meta-analyses support probiotics for cognitive impairment.$^{79-81}$ Other meta-analyses, however, report mixed results, highlighting the need for continued investigation to clarify causal mechanisms, identify reliable biomarkers, and define optimal, tailored interventions.$^{82,83}$ Nevertheless, the gut-brain axis is a modifiable driver of brain health, suggesting that preserving microbial diversity and gut barrier function may promote cognitive resilience. Although strain- and dose-specific guidance for probiotics, prebiotics, and fecal microbiota transplantation

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is not yet sufficiently standardized to support universal recommendations, current evidence supports increasing dietary fiber through various plant-based foods, reducing ultraprocessed foods and added sugars, and including fermented foods such as yogurt, kefir, or kimchi, as these strategies are consistently associated with enhanced microbial diversity and metabolite production.

POOR SLEEP QUALITY

Across the life span, sleep appears to evolve with the brain, playing an important role in development, memory, and disease prevention. In early childhood, frequent naps and slow wave brain activity support hippocampal maturation and long-term memory consolidation.$^{84}$ Self-reported sleep duration among adolescents has decreased over the past 2 decades, which has been identified as a global public health concern. Inflammation and oxidative stress are again implicated as mechanisms of cerebrovascular injury and cognitive dysfunction.$^{85}$

Duration of sleep in adulthood is thought to preserve gray matter volumes in key areas serving cognition (ie, hippocampus and frontal cortex).$^{86}$ In addition, sleep supports memory consolidation, synaptic downscaling, and clearing of proteins through the lymphatic system. $^{84,87,88}$. Inadequate sleep or poor sleep quality is associated with cognitive decline and dementia, in part through impaired removal of toxic β-amyloid and other substances from the brain.$^{89-91}$ Accumulation of β-amyloid and tau may, in turn, disrupt the sleep-wake cycle, $^{92}$ leading to increased sleep fragmentation and wakefulness and decreased slow-wave sleep.$^{93}$ Medical conditions, such as obstructive sleep apnea, may increase the risk of cognitive decline and dementia by interfering with blood flow to the brain and patterns of brain activity that promote memory and attention.$^{94,95}$

Mechanistically, sleep and sleep patterns support brain homeostasis. Policy-level perspectives have recently emphasized "sleep capital" as a key investment in brain health, cognitive resilience, and economic productivity throughout life. Sleep capital is conceptualized as the cumulative social, economic, and health gains derived from maintaining adequate sleep and light exposure across the life span. By quantifying returns on brain health, job performance, long-term physical and mental health, and societal productivity, this framework underscores sleep as a cornerstone of developmental success and aging well.$^{96}$

SOCIOECONOMIC FACTORS AND ADVERSE CHILDHOOD EXPERIENCES

Researchers have long reported a negative association between years of formal education and risk for cognitive

decline and dementia, attributing this to higher cognitive reserve among more highly educated individuals.$^{97-103}$ More recently, research examining the complex relationships among education and socioeconomic status (SES)—broadly defined as access to economic resources such as income, employment, and financial security—has linked fewer years of formal education with lower SES.$^{104}$ Lower SES, in turn, is associated with greater risk of diabetes$^{105-107}$ and hypertension,$^{108}$ both of which are risk factors for cognitive decline and dementia.$^{107}$ Racial inequities have been broadly linked to the global burden of stroke and cardiovascular disease, as well as to disparities in overall brain health.$^{109}$

Along with SES, other social determinants of health can affect the risk of cognitive decline and dementia by decreasing one's access to foods that support brain health,$^{110-112}$ health care or medical treatments, and stable housing. Adverse childhood experiences (ACEs), which include abuse (eg, physical, emotional, sexual), neglect (eg, physical, emotional, intrauterine substance exposure), and exposure to household challenges (eg, mental illness, domestic violence, parental separation or divorce, incarceration, substance misuse or dependence)$^{113}$ are experienced by many individuals; 17.3% of US adults report having experienced ≥4 ACEs.$^{114}$ ACEs increase the risk for learning and attention difficulties in childhood, as well as mental health conditions, neurovascular events, and Alzheimer and other dementias with aging.$^{115}$ An accumulation of ACEs can lead to prolonged and excessive activation of the hypothalamic-pituitary-adrenal axis, resulting in persistently elevated cortisol levels and excessive glucocorticoid receptor activation. Rather than engaging the usual homeostatic processes in response to transient stress exposure, a dysregulated hypothalamic-pituitary-adrenal axis has implications for multiple biologic systems and may result in hyperelevated cortisol levels and allostatic overload, commonly referred to as a "toxic stress response."$^{116}$ Alterations in catecholamine signaling and autonomic nervous system dysregulation in response to early life stress may also influence brain development.$^{117,118}$

Systemic inflammatory, endocrine, and metabolic disruptions resulting from accumulation of ACEs have implications for neurobiologic health. For example, elevated cortisol levels can contribute to atherosclerosis progression and impaired glucose metabolism, both of which can have cumulative damaging effects on brain health over time. Emerging evidence implicates epigenetics (molecular mechanisms governing gene expression and cellular functions) in mediating the body's toxic stress response. A key goal of screening for ACEs is to identify who may be at risk of a toxic stress response, by considering the type, timing, and duration of adversity, as well as exacerbating factors, versus the presence of supports and protective factors within the environment. Early identification

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of those at risk allows for the introduction of strategies to prevent or mitigate risk.$^{115}$ In addition to psychotherapy, evidence-based interventions focus on ensuring a safe, healing, and cognitively stimulating environment to support healthy brain development through interactive play, consistent reading, regular physical activity, a balanced diet, and sufficient sleep. Limiting screen time, facilitating opportunities to be out in natural outdoor settings, and managing stress are key to promoting optimal cognitive function; however, low SES, geographic constraints, exposure to systemic racism, historical underrepresentation of racial or ethnic groups, and discrimination are social determinants of health that can greatly impede functional outcomes.$^{119}$

EARLY LIFE INFECTION AND CHRONIC MEDICAL CONDITIONS

Whereas medical conditions can affect brain health across the life span, there are key differences between pediatric- and adult-onset illness. For example, atherosclerosis-on the causal pathway for many factors affecting adult brain health-begins in childhood but is unlikely to affect pediatric brain health. A study of patients with ischemic stroke across the life span found that atherosclerotic factors do not emerge as risk factors for overt stroke until young adulthood.$^{120}$ There is, however, mounting evidence that chronic nonatherosclerotic cardiovascular and cerebrovascular diseases of childhood affect brain development, cognitive function, and mental health. These pediatric diseases are heterogeneous, including congenital heart disease$^{121}$; hematologic diseases, such as sickle cell anemia; and poorly understood cerebral arteriopathies, such as moyamoya. These diseases have in common impaired cerebral perfusion, which has been shown to disrupt the normal formation of neural networks in the brain and lead to cognitive impairment.$^{122,123}$ In other childhood diseases, cerebrovascular injury with secondary cognitive impairment is a consequence of treatment. Cranial radiation, needed for the treatment of many malignancies, injures cerebral arteries, in addition to its direct neurotoxic effects. Each of these chronic pediatric diseases can have indirect implications for brain health, such as the physiologic stress of frequent hospitalizations and procedures, or the reduced ability to exercise because of limited exercise tolerance, school absenteeism, child/parent/family psychologic stress, and genetic and epigenetic factors. In addition, obesity-a risk factor for vascular brain health-can drive insulin resistance, inflammation, vascular injury, and hormonal imbalances, each of which independently impairs cognition and brain structure at all stages of life.$^{124-126}$ Recent advances suggest opportunities to preserve brain health in children at elevated cerebrovascular risk.

In sickle cell disease, for example, hydroxyurea protects against silent brain infarcts and helps maintain cognitive function.$^{127}$

Environmental and lifestyle factors also affect cerebrovascular health and cognitive function in childhood. As discussed previously, many of these factors are associated with social determinants of health, which are intrinsically linked to where people are born, play, learn, live, work, and age. These factors have direct and indirect links to chronic disease, childhood stroke risk, and neurologic and mental health outcomes.$^{128}$ Whereas diet and exercise are commonly recognized as modifiable vascular risk factors, major and minor infections are also associated with increased risk of stroke in childhood. Minor infection in the week before arterial ischemic stroke is common across stroke subtypes and demonstrates seasonal variation.$^{129}$ In addition, poor vaccination status is an independent predictor of childhood stroke. Infection is associated with stroke through multiple direct and indirect mechanisms that may affect the arteries of the circle of Willis, trigger inflammation, and cause thromboembolism.

 Physical and psychologic risk factors beginning prena-tally have a considerable impact on brain maturation and overall cognitive health throughout the life span (Figure 3). This scientific statement underscores the sign-ificance of early detection, prevention, and intervention initiatives in promoting optimal brain health across life. Factors such as epigenetics likely influence why individual-als with similar exposures can experience varying out-comes. Further research is needed to fully understand these complex relationships.

As a first step, we emphasize the intrinsic link between neurologic and mental health in aging, urging health care professionals, policymakers, and the general public to prioritize comprehensive strategies that safeguard and promote brain health from the prenatal period through adulthood across all communities. Action must be taken to understand and address the needs of communities that traditionally have had unequal access to preventive health information and services. As a leading principle of prevention of neurodegeneration and cerebrovascular disease, we advocate for a holistic approach that integrates the biopsychosocial framework within traditional medical practice to ensure development, testing, and implementation of interventions across the life span to promote brain health and mental well-being. By implementing personalized, culturally responsive, evidence-based practices and advancing research in medicine, neuropsychiatry, behavioral neurology, psychology, and geroscience, we can extend health, longevity, and independence in aging adults.

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 Figure 3. Factors impacting brain health across the life span.

ARTICLE INFORMATION

The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.

This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on January 7, 2026, and the American Heart Association Executive Committee on March 2, 2026. A copy of the document is available at https://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 215-356-2721 or email Meredith.Edelman@wolterskluwer.com

The American Heart Association requests that this document be cited as follows: Marsh EB, Lavretsky H, Kasparian NA, Pike NA, Doyle KP, Aggarwal

NT, Fullerton HJ, Ivy AS, Dlamini N; on behalf of the American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Clinical Cardiology. Brain health across the life span: a framework for future studies: a scientific statement from the American Heart Association. Stroke. 2026;57:e**-e***. doi: 10.1161/STR.0000000000000518

The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit https://professional.heart.org/statements. Select the "Guidelines & Statements" drop-down menu, then click "Publication Development."

Permissions: Multiple copies, modification, alteration, enhancement, and distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at https://www.heart.org/permissions. A link to the "Copyright Permissions Request Form" appears in the second paragraph (https://www.heart.org/en/about-us/statements-and-policies/copyright-request-form).

CLINICAL STATEMENTS AND GUIDE INES

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Disclosures

Writing Group Disclosures

|Writing group member|Employment|Research grant|Other research support|Speakers&#x27; bureau/ honoraria|Expert witness|Ownership interest|Consultant/ advisory board|Other| |---|---|---|---|---|---|---|---|---| |Elisabeth Breese Marsh|Johns Hopkins School of Medicine|None|None|None|None|None|None|None| |Helen Lavretsky|UCLA|None|None|None|None|None|None|None| |Neelum T. Aggarwal|Rush University Medical Center, Rush Alzheimer&#x27;s Disease Center|NIH (R01 AG062637-01)*|None|None|None|None|None|None| |Nomazulu Dlamini|The Hospital for Sick Children (Canada)|None|None|None|None|None|None|None| |Kristian P. Doyle|Department of Neurology, University of Arizona, Tucson|Precision Aging Network (coinvestigator on an NIA-funded grant investigating ways to optimize brain health over the life span)*|None|None|None|None|None|None| |Heather J. Fullerton|University of California San Francisco, Weil Institute for Neurosciences|NIH (research on pediatric stroke)†|None|None|None|None|None|None| |Autumn S. Ivy|Kennedy Krieger Institute|None|None|None|None|None|None|None| |Nadine A. Kasparian|Cincinnati Children&#x27;s Hospital Medical Center, Heart Institute, Heart and Mind Wellbeing Center|None|None|None|None|None|None|None| |Nancy A. Pike|University of California Irvine School of Nursing|NIHt|None|None|None|None|None|None|

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives ≥$5000 during any 12-month period, or ≥5% of the person's gross income; or (b) the person owns ≥5% of the voting stock or share of the entity, or owns ≥$5000 of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition.

*Modest.

†Significant.

Reviewer Disclosures

|Reviewer|Employment|Research grant|Other research support|Speakers&#x27; bureau/ honoraria|Expert witness|Ownership interest|Consultant/ advisory board|Other| |---|---|---|---|---|---|---|---|---| |Julia Kate Boehm|Chapman University|American Heart Association (research grant 24AIREA1196638 to investigate how psychosocial resources, including well-being, are related to cardiovascular health in adults)†|None|None|None|None|None|None| |William G. Mayhan|University of South Dakota|None|None|None|None|None|None|None| |Kamal Rahmouni|The University of Iowa|None|None|None|None|None|None|None| |Farzaneh A. Sorond|Northwestern University|None|None|None|None|None|None|None|

This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be "significant" if (a) the person receives ≥$5000 during any 12-month period, or ≥5% of the person's gross income; or (b) the person owns ≥5% of the voting stock or share of the entity, or owns ≥$5000 of the fair market value of the entity. A relationship is considered to be "modest" if it is less than "significant" under the preceding definition.

*Modest.

†Significant.

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Stroke FIRST PROOF ONLY