Dementia and Cognitive Decline: A HEALM Approach

Abstract

Dementia and cognitive decline pose significant global public health challenges, with prevalence expected to rise in the coming decades. Lifestyle medicine offers a promising approach to mitigating cognitive issues through six key interventions: diet, physical activity, restorative sleep, social connections, stress management, and avoiding risky substances. Traditional methods like randomized controlled trials (RCTs) have limitations in capturing the long-term impacts of these interventions. To overcome these challenges, the American College of Lifestyle Medicine (ACLM) and the True Health Initiative (THI) developed the Hierarchies of Evidence Applied to Lifestyle Medicine (HEALM) framework, informed by the Evidence Threshold Pathway Mapping (ETPM) approach. This framework integrates diverse evidence sources to assess intervention effects over time. Applying HEALM, this review evaluates lifestyle factors’ impact on dementia and cognitive decline. It finds strong evidence supporting plant-based nutrition, physical activity, restorative sleep, and avoiding risky substances in promoting cognitive health. Social connections may mitigate cognitive decline, while stress management requires further investigation due to inconclusive findings. Integrating these findings into public health strategies could effectively address the growing dementia burden and enhance overall well-being in aging populations, underscoring the need for continued research in cognitive health.

“Physical activity modulates neurobiological pathways essential for maintaining cognitive vitality.”

Introduction

Dementia and cognitive decline are significant public health challenges affecting millions globally. With the aging population, the prevalence of dementia is expected to rise from 55 million to 75 million by 2030, and 131 million by 2050. ¹ The financial burden, which was $305 billion in 2020, is projected to triple by 2050.^2,3 Cognitive decline ranges from mild impairment to severe dementia, with Alzheimer’s disease (AD) being the most common. These conditions impact memory, cognitive abilities, daily functioning, autonomy, and quality of life, highlighting the urgent need for effective interventions and strategies. ⁴

The field of lifestyle medicine, encompassing diet, exercise, sleep, social connections, stress management, and substance use, faces scrutiny regarding evidence supporting specific recommendations. Traditional randomized controlled trials (RCTs) may not fully capture the long-term effects and complexities of lifestyle interventions due to methodological challenges such as cost, adherence, and generalizability. ⁵

In response, the American College of Lifestyle Medicine (ACLM) and True Health Initiative (THI) collaborated to develop a systematic review methodology aimed at evaluating existing strength of evidence (SOE) in lifestyle medicine. ⁵ Their approach, integrating the Evidence Threshold Pathway Mapping (ETPM) and Hierarchies of Evidence Applied to the Lifestyle Medicine (HEALM) framework, seeks to assess lifestyle interventions holistically. ETPM guides decision-making on evidence assessment, recognizing the contributions of diverse study designs to understand treatment effects over time. ⁵ Derived from ETPM, HEALM focuses on long-term effects and integrates experimental science, intervention studies, and observational epidemiology to provide nuanced conclusions on lifestyle intervention effectiveness. ⁵ See Table 1.

Table 1.

Hierarchies of Evidence Applied to Lifestyle Medicine (HEALM) Strength of Evidence (SOE) Approach. ⁵

HEALM contains three scoring levels of SOE:

Grade A (Strong/decisive) ≥7. It would require decisive evidence in all other categories, AND at least suggestive evidence from intervention trials in people; OR strong evidence from intervention trials in people, and decisive evidence in other two categories; OR strong evidence from intervention trials, decisive evidence in any other category, and suggestive evidence in the remaining two. It lends a primacy to RCT evidence but allows for strong evidence even with nothing more than suggestive evidence in the intervention trial category.

Grade B (Moderate/suggestive) 5 or 6. Achievable with decisive intervention trial evidence and strong evidence in ANY other category. OR, strong evidence in all categories other than intervention trials.

Grade C (Insufficient/inconclusive) < 5

Q1: Are there established mechanisms of action?

(plurality a of evidence from bench science and animal models)

Yes = 2

Uncertain = 1

No = 0

Q2: Are there intervention studies in people that provide evidence of causality/attribution?

(a plurality a of high-quality intervention trials, randomized controlled trials, interim measures, and surrogate markers as outcomes)

Yes = 3

Uncertain = 1

No = 0

Q3: Are there observational studies to establish generalizability to a large population? (a plurality studies)

Yes = 2

Uncertain = 1

No = 0

Q4: Are they measured in decades, lifetimes, or generations?

(plurality a of evidence from high quality, long-term observational studies; retrospective cohort studies; ethnography; transcultural studies)

Yes = 2

Uncertain = 1

No = 0

^aPlurality may vary depending on the total number of existing studies conducted on a particular research question and must be determined case-by-case. For example, three consistent studies from various study designs with no opposing studies may constitute a plurality. If there were opposing studies, the target number would be more than three. A clear numerical plurality of studies but with overall poor quality may constitute a rating of “Uncertain.”

This review aims to evaluate the impact of lifestyle choices on health outcomes, considering the six pillars of lifestyle medicine. Applying the HEALM framework seeks to elucidate how these interventions influence short- and long-term health outcomes and quality of life in individuals managing dementia and cognitive decline.

Plant-Based Nutrition

Plant-based nutrition, emphasizing diets rich in fruits, vegetables, whole grains, nuts, and seeds, has garnered attention for its potential health benefits, particularly in cognitive health and dementia prevention. ⁶ Emerging studies suggest that these diets offer antioxidants, anti-inflammatory compounds, and essential nutrients that support brain health and cognitive function. ⁷ Diets like the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND), which emphasize plant-based foods, show promise in reducing the risk of dementia and slowing cognitive decline by addressing oxidative stress and inflammation, both critical factors in dementia development. ⁷

Additionally, these dietary patterns promote vascular health by ensuring sufficient blood flow to the brain. ⁸ As research progresses, plant-based nutrition is increasingly recognized as a promising, accessible, and sustainable approach to supporting cognitive health and potentially reducing the incidence of dementia.

Q1: Are There Established Mechanisms of Action? (Yes = 2)

Research suggests that a plant-based diet may significantly reduce the risk for AD by maintaining a favorable blood lipid profile low in saturated fats and cholesterol. ⁹ They are rich in phytonutrients such as vitamins, antioxidants, and dietary fiber, which collectively support cognitive health and may reduce the risk of cognitive decline associated with AD. ⁹ Additionally, compounds like quercetin in plant-based diets act as natural monoamine oxidase inhibitors, potentially offering protective benefits against AD. ⁹

In Asian populations, regular consumption of salt-preserved vegetables, including popular dishes like kimchi, has been linked to lower risks of cognitive impairment due to their micronutrient content, such as vitamin B12 and vitamin E, known for their cognitive benefits. ¹⁰ Studies highlight the Mediterranean diet as another potent alternative to reduce AD risk. High adherence to the Mediterranean diet has been associated with a 53% reduction in AD risk, while even moderate adherence still provides a substantial 35% decrease. ¹¹

The Mediterranean dietary pattern, rich in plant-based foods, supports brain health through mechanisms like omega-6 polyunsaturated fatty acids that aid in clearing amyloid-beta (Aβ), an essential protein in AD pathology. ¹¹ Vitamin D in these diets also helps inhibit Aβ-induced apoptosis, further protecting brain cells from degeneration. ¹¹ Moreover, plant-based diets positively influence the gastrointestinal microbiome, which contributes to neurotransmitter production and the gut-brain axis, potentially leading to their neuroprotective effects. ¹²

Q2: Are There Intervention Studies in People That Provide Evidence of Causality/Attribution? (Yes = 3)

The “Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Study” is a 3-year randomized controlled trial investigating the MIND diet’s effects on cognitive function in 604 individuals at risk for AD. ¹³ Participants aged 65 to 84 were assigned to either the MIND diet with mild caloric restriction or their usual diet with mild caloric restriction. ¹³ The study includes cognitive assessments, medical history, blood and urine samples, and magnetic resonance imaging (MRI) scans of brain structure at the start and end. ¹³ It focuses on a comprehensive dietary pattern rather than individual nutrients and aims to provide insights into the diet’s potential effects on AD prevention. ¹³ Results are still being analyzed but are anticipated to guide future dietary recommendations for AD prevention. ¹³

Another study highlights the role of diet in AD, emphasizing neuroprotective nutrients such as antioxidants, B vitamins, and polyunsaturated fatty acids. It suggests that diets like the Mediterranean, DASH, and MIND diets may help lower the risk of developing AD. ⁷

Population-based studies further highlight long-term nutritional impacts on cognitive health. The PATH Through Life cohort in Canberra showed higher adherence to the MIND diet, correlated with reduced cognitive impairment odds over 12 years. ¹⁴

Similarly, research on the Three-City Bordeaux cohort in France linked a higher French-adapted MIND diet score with lower risks of dementia and AD alongside preserved white matter microstructure. ¹⁵ In contrast, findings from the UK Biobank, involving 120,661 participants, revealed mixed results. While the MIND diet did not broadly improve cognitive test scores or overall dementia risk, it did lower dementia risk specifically among women, indicating potential sex-specific benefits. ¹⁶ These studies collectively emphasize dietary patterns’ impact on cognitive health, yet variations in outcomes stress the need for further diverse population research to clarify these relationships.

Q3: Are There Observational Studies to Establish Generalizability to Large Populations? (A Plurality Studies). (Yes = 2)

Several observational studies highlight the critical role of dietary choices in cognitive health, emphasizing the impact of the MIND diet on reducing dementia risk. The Rotterdam Study, involving a substantial cohort of 5375 participants initially, followed by 2861 more in subsequent phases, with long-term follow-up periods averaging 15.6 and 5.9 years, provides compelling evidence for the MIND diet’s protective effects against dementia. ⁶ Insights into neuroprotective nutrients and foods highlight the benefits of vitamin E, B vitamins, n-3 fatty acids, and specific dietary items like green leafy vegetables, berries, and seafood in reducing dementia risk. ⁶

A comprehensive review on nutrition and cognitive health links diets such as the Mediterranean, Nordic, DASH, and MIND to a lower risk of cognitive decline and dementia, emphasizing the gut-brain axis and advocating early preventive strategies in midlife to manage cardiometabolic risk factors associated with dementia. ⁸ Research on dietary patterns and AD risk contrasts the adverse effects of high-fat, high-meat, and high-energy diets with the protective effects of diets rich in fruits, legumes, nuts, omega-3 fatty acids, vegetables, and whole grains. ¹⁷ The study suggests dietary strategies to decrease risks like inflammation, insulin resistance, and oxidative stress. ¹⁷

Finally, a review of dietary patterns and cognitive decline highlights the multifaceted factors influencing cognitive health, including age, genetics, socio-economic status, education, and environmental determinants like nutrition. ¹⁸ It suggests the potential of diets like the Mediterranean, DASH, and MIND in slowing cognitive decline and reducing dementia risk on a public health scale. ¹⁸

Q4: Are They Measured in Decades, Lifetimes, or Generations? (Yes = 2)

Most studies on diet and cognitive health measured effects over decades, with some spanning entire lifetimes. The MIND study, a 3-year RCT, assesses its long-term impact due to the nature of cognitive decline and neurodegenerative diseases. ¹³ Several reviews highlight the lifelong effect of diet on AD prevention and emphasize long-term dietary habits. ⁷ Longitudinal cohort studies, which measure cognitive impairment over extended periods, such as 12 years, demonstrate the necessity of long-term observation. ¹⁴ Additionally, studies have linked dietary patterns with brain structure and dementia over decades. ¹⁵

A study analyzing data from the UK Biobank assessed cognitive outcomes and dementia incidence over long-term periods, typically spanning decades. ¹⁶ The Rotterdam Study includes follow-up periods averaging 15.6 and 5.9 years, indicating long-term observations. ⁶ Comprehensions overviews discuss the long-term impact of nutrition on dementia risk over an individual’s lifetime, while other studies examine nutrition’s influence on cognitive health from early life to old age.^8,19 Reviews explore dietary influences on AD risk over a lifetime and discuss dietary patterns for cognitive decline prevention over long-term periods.^17,18

Score = 9, Grade A (Strong/decisive) ≥7

Current studies provide strong evidence supporting plant-based nutrition as an effective lifestyle intervention for reducing the risk of dementia and cognitive impairment. Diets like the Mediterranean, DASH, and MIND, which emphasize plant-based foods rich in antioxidants and anti-inflammatory compounds, promise to reduce oxidative stress and inflammation, critical factors in dementia development. These diets support vascular health, ensuring adequate brain oxygenation and nutrient supply. Both intervention and observational studies consistently suggest that these dietary patterns can slow cognitive decline and potentially prevent AD.

While further research is needed to refine these findings, the overall positive outcomes across multiple studies accentuate plant-based nutrition’s potential as an accessible and sustainable strategy for promoting cognitive health. Integrating these diets into public health initiatives could be vital in addressing the increasing incidence of dementia and improving the well-being of aging populations.

Physical Activity

Recent research highlights the profound impact of physical exercise on cognitive function, extending beyond its well-established benefits for physical health. Studies emphasize that exercise enhances various cognitive processes, including memory, attention, executive function, and decision-making. ²⁰ This connection has spurred interest in understanding the mechanisms underlying exercise-induced cognitive improvements and exploring exercise interventions as non-pharmacological strategies for enhancing cognitive function across the lifespan. ²¹ Research indicates that exercise promotes neurobiological changes such as neurogenesis, synaptic plasticity, modulation of neurotransmitter levels, and reduction of neuroinflammation, which are fundamental for maintaining cognitive vitality.^22,23

These findings suggest that investigating the relationship between exercise and cognition could reveal new paths for cognitive enhancement and potentially alleviate cognitive decline associated with aging and neurodegenerative diseases like AD. ⁴

Q1: Are There Established Mechanisms of Action? (Yes = 2)

Physical activity (PA) profoundly impacts cognitive function through multiple interconnected mechanisms. Firstly, it enhances brain plasticity by stimulating the production of neurotrophic factors like brain-derived neurotrophic factor (BDNF), which promote neuronal growth, survival, and synaptic plasticity. ²³ This supports improved learning, memory, and cognitive skills.^23,24 Exercise also preserves synaptic function by promoting the formation of new synapses and maintaining existing ones, facilitating efficient neuronal communication critical for optimal cognitive function. ²³ Additionally, PA is essential for maintaining mitochondrial health and vital for cellular energy production and neuronal function. ²³

Exercise promotes mitochondrial biogenesis, dynamics, and autophagy, reducing oxidative stress and enhancing brain adenosine triphosphate (ATP) production.^23,25 Key regulators like Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α), mitogen-activated protein kinases (MAPK), and silent mating type information regulation two homologue 1 (SIRT1) are activated through exercise, supporting mitochondrial health.^23,25,26 Exercise-induced cytokines released from skeletal muscle, such as irisin, clusterin, and glycosylphosphatidylinositol specific phospholipase D1 (Gpld1), can cross the blood-brain barrier to benefit the brain. These cytokines enhance synaptic plasticity, reduce inflammation, and provide neuroprotection, particularly relevant in neurodegenerative diseases like AD.^23,27,28

Irisin, derived from Fibronectin type III domain-containing protein 5 (FNDC5), supports synaptic plasticity and memory through the cAMP/PKA/CREB pathway, contributing to exercise-induced neuroprotection.^23,28 Lastly, PA influences gut microbiota composition, increasing diversity and promoting beneficial bacteria growth. This process produces short-chain fatty acids (SCFAs) essential for energy metabolism and metabolic flexibility.^23,29,30

Q2: Are There Intervention Studies in People That Provide Evidence of Causality/Attribution? (Yes = 3)

Exercise interventions, including aerobic, resistance training, and mind-body practices like Tai Chi and yoga, enhance cognitive function among older adults, particularly those leading sedentary lifestyles.^31,32 These interventions consistently improve global cognition, executive function, and memory.^31,32 However, evidence regarding exercise’s efficacy in reducing dementia risk post-mild cognitive impairment (MCI) remains limited and subject to bias in meta-analyses.^31,32 Longitudinal cohort studies, such as those from the 1946 British birth cohort, highlight that maintaining PA across adulthood correlates with better cognitive performance and verbal memory scores later in life. ³³ Lifelong PA engagement benefits cumulative cognitive function, emphasizing sustained exercise habits. ³³

Additionally, observational studies from Blue Zones—regions known for their high longevity and low incidence of chronic diseases—support these findings. ³⁴ In Blue Zones, regular physical activity, including walking, is a common lifestyle factor associated with improved cognitive health and longevity. ³⁴

Aerobic exercise significantly benefits global cognitive and executive functions, while resistance training’s impact, particularly on short-term memory, appears more modest. ³⁵ Functional MRI studies suggest exercise-induced changes in brain regions may contribute to improved cognitive performance, but the research noted limitations such as small sample sizes and moderate methodological quality. ³⁵ Meta-analytical findings indicate that regular exercise enhances global cognition and activities of daily living in individuals with AD, especially with consistent sessions over more extended periods. ³⁶

However, exercise does not significantly improve cognitive function in healthy older adults without cognitive impairment despite enhancing cardiorespiratory fitness. ³⁷ For individuals with dementia, exercise programs may improve daily activity performance but show limited cognitive or psychological benefits. ³⁸

Q3: Are There Observational Studies to Establish Generalizability to Large Populations? (A Plurality Studies). (Yes = 2)

In a study of 2074 older Chinese individuals, those who exercised (1372 participants) showed improved cognitive function, particularly in visuospatial abilities, compared to non-exercisers (702 participants), reducing dementia risk. ³⁹ However, the groups had no significant differences in blood lipid profiles or brain anatomy. ³⁹

Observational studies and meta-analyses over 1 to 12 years consistently link higher PA levels to reduced cognitive decline and dementia risk, including AD. Meta-analyses with large sample sizes support this association. ²⁴

A meta-analysis of 54 RCTs involving 6277 participants found that exercise interventions positively impacted global cognition, executive function, memory, attention, and information processing. ⁴⁰ Aerobic exercise improved global cognition. Resistance exercise enhanced executive function, and mind-body exercises showed promise for memory enhancement, particularly in older adults (>60 years). ⁴⁰

Studies, such as the Framingham Heart Study and the Women’s Health Initiative, involve thousands of participants and demonstrate that regular walking is associated with better cognitive outcomes and a reduced risk of cognitive decline. ³⁴

A longitudinal study in Korea with 4825 participants from 2010 to 2018 indicated that continuous exercise may slow cognitive decline over time, even in those genetically predisposed to dementia. ⁴¹ Exercise benefited cognitive function in individuals with MCI and dementia, though its effects on those with normal cognition were uncertain. ⁴¹ Any level of exercise showed effects on cognitive function in the dementia group compared to no exercise. ⁴¹ However, meeting the WHO guideline of ≥150 minutes per week did not provide additional benefits. ⁴¹ The study emphasizes the importance of regular exercise interventions for older adults, especially those with cognitive impairment.

Q4: Are They Measured in Decades, Lifetimes, or Generations? (Yes = 2)

The 1946 British birth cohort study investigated how lifelong PA influences cognitive function at age 69. ³³ Participants (n = 1417, 53% female) reported leisure time PA levels five times between ages 36 and 69. ³³ Results indicated that any level of exercise in adulthood was linked to higher cognitive function at age 69, with sustained cumulative activity showing the most substantial impact. ³³ This study measured PA and cognitive function over several decades of adulthood, emphasizing the lifelong effect of PA on cognitive health.

Furthermore, this review highlights two main discoveries. First, cross-sectional research shows that higher cardiorespiratory fitness is linked to better cognitive function, with baseline fitness predicting cognitive performance across various domains six years later. ⁴² Second, longitudinal studies reveal that older adults who engage in physical activity experience slower cognitive decline over two to 10 years. ⁴²

In Blue Zones, the benefits of physical activity like walking are measured over decades. ³⁴ Studies focus on how consistent physical activity influences cognitive health and longevity over extended periods, demonstrating the long-term positive effects on cognitive function and overall well-being. ³⁴

The evidence regarding PA and its impact on cognitive decline and dementia is primarily derived from prospective observational studies spanning 1 to 12 years. ²⁴ Strong evidence suggests that higher levels of PA are linked to a decreased risk of cognitive decline and dementia, including AD. ²⁴ Meta-analyses of these studies, encompassing over 33,000 participants, indicate a 38% reduced risk of cognitive decline and a 40% reduced risk of developing AD associated with more significant amounts of PA. ²⁴ However, the effectiveness of PA interventions in preventing dementia is inconclusive, with some studies suggesting potential benefits but others indicating insufficient evidence. ²⁴

Score = 9, Grade A (Strong/decisive) ≥7

The review presents strong evidence from intervention studies, including RCTs and meta-analyses, demonstrating that various types of exercise—like aerobic, resistance, and mind-body exercises—enhance cognitive function in older adults. These exercises improve global cognition, executive function, and memory. Observational studies and large-scale meta-analyses further validate these benefits, indicating that higher levels of PA are associated with reduced cognitive decline and dementia risk, including AD. The review also highlights that Blue Zones, where PA is integral to daily life, show long-term cognitive health benefits, reinforcing the value of exercise. However, the review acknowledges limitations, such as inconclusive evidence regarding exercise’s effectiveness in preventing dementia and variability in study quality. Despite these challenges, the review strongly supports the link between PA and cognitive function, advocating for regular exercise interventions among older adults, particularly those with cognitive impairment.

Restorative Sleep

Quality sleep is fundamental for optimal cognitive function, supporting memory consolidation, problem-solving, creativity, and emotional regulation. ⁴³ Adequate sleep fosters attention and concentration, which are essential for effective learning. ⁴⁴ The brain processes information during deep sleep, enhancing long-term memory. ⁴³ Sleep also facilitates toxin removal from brain cells, supporting cognitive health.^43,44

Conversely, sleep deprivation can impair attention, memory, motor skills, and speech, posing safety risks like drowsy driving. ⁴³ Chronic sleep problems may increase the risk of cognitive decline and dementia, with estimates suggesting that improved sleep could prevent 15% of AD cases. ⁴³ Prioritizing high-quality sleep is essential for maintaining cognitive function and reducing age-related decline.

Q1: Are There Established Mechanisms of Action? (Uncertain = 1)

Individuals with mild cognitive impairment and dementia often experience exacerbated sleep issues, with disrupted sleep patterns and disorders accelerating neurodegenerative conditions’ onset and progression. ⁴⁴ However, the precise pathogenic mechanisms linking sleep disturbances to dementia development remain uncertain. ⁴⁴ It is hypothesized that degeneration of neural pathways regulating sleep-wake patterns contributes to these disturbances. ⁴⁴

Insufficient or excess sleep, poor quality, circadian disruptions, insomnia, and obstructive sleep apnea are associated with a higher risk of cognitive impairment and dementia. ⁴³ The sleep-wake cycle influences Aβ levels, which are central to AD. ⁴⁵ Additionally, abnormal tau proteins linked to AD may spread through neural networks, potentially exacerbated by sleep deprivation. ⁴⁶

Q2: Are There Intervention Studies in People That Provide Evidence of Causality/Attribution? (Yes = 3)

Since cerebrospinal fluid (CSF) Aβ levels increase with sleep deprivation, chronic sleep issues have been thought to contribute to an increased risk of AD. ⁴⁶ A study published in 2020 measured concentrations of tau and phosphorylated tau in serial samples of CSF taken from individuals who were either sleep-deprived, treated with sodium oxybate, or permitted to sleep usually. ⁴⁶ Neuronal activity contributes to the release of tau, which has been observed to rise in the interstitial fluid of mice and human CSF during sleep deprivation. ⁴⁶ It was found that sleep loss had a varying effect on phosphorylated tau depending on the modified site. ⁴⁶ Tau hyperphosphorylation is associated with neurofibrillary tangles and eventual cognitive dysfunction. ⁴⁶ This research suggests a causal or associative mechanism for how sleep loss heightens susceptibility to AD.

Notably, however, interventions attempting to boost cognitive function in older adults via sleep quality have had mixed results. ⁴⁷

Q3: Are There Observational Studies to Establish Generalizability to Large Populations? (A Plurality Studies). (Yes = 2)

Substantial observational evidence supports the hypothesis that sleep disturbances (including duration, fragmentation, insomnia, idiopathic rapid eye movement (REM) disorder, sleep movement disorders, and medication use) increase the risk of cognitive impairment and dementia. ⁴⁷ Various indicators of suboptimal sleep quality, including reduced sleep efficiency, longer time to fall asleep, wakefulness after sleep onset, and daytime napping, have all been linked to impaired cognitive function in both cross-sectional and prospective studies conducted over a year. ⁴⁵

Extensive observational studies measured by actigraphy have shown that sleep fragmentation increases the risk of dementia. ⁴⁸ This includes studies in which sleep fragmentation was the result of sleep-disordered breathing. ⁴⁸

A pooled cohort study of 28,756 individuals published in 2020 showed that the decline in global cognitive function in people with extremely low or high sleep duration was statistically significant compared to a reference cohort (7 hours of sleep per night) after adjusting for confounding variables. ⁴⁹ This study included 100,000 person-years of follow-up. ⁴⁹ Another study observed the relationship between longitudinal sleep disturbance measures and dementia using a national USUS cohort, making the findings generalizable to the population. ⁴⁷

Q4: Are They Measured in Decades, Lifetimes, or Generations? (Yes = 2)

The studies mentioned above span various durations, with some focusing on short-term effects while others extend across decades or even lifetimes. For example, one study observed the relationship between longitudinal sleep disturbance measures and dementia using ten annual waves of data from the NHATS, a survey of Medicare beneficiaries aged 65 and older. ⁴⁷ Another study found a higher risk of dementia associated with sleep durations under six hours at ages 50 and 60, using a 25-year follow-up with 7959 participants. ⁵⁰ A pooled cohort study, including 100,000 person-years of follow-up, demonstrated significant declines in global cognitive function among individuals with very low or high sleep durations. ⁴⁹ A review explored sleep physiology and disorders across the lifespan, mainly focusing on aging and dementia. ⁴⁴ Systematic reviews and meta-analyses explored the long-term relationship between sleep, cognitive impairment, and AD. ⁴³ Another review included the bidirectional relationship between sleep and AD pathology throughout a lifetime. ⁴⁵ Longitudinal studies on sleep patterns and cognitive impairment in older adults spanned extended periods. ⁵¹ Lastly, investigations explored how sleep fragmentation influences dementia risk and cognitive decline in older individuals over their remaining lifespan. ⁴⁸

Score = 8, Grade A (Strong/decisive) ≥7

Current studies provide strong evidence that restorative sleep is a critical lifestyle factor for preventing dementia and cognitive impairment. Disrupted sleep patterns significantly impact cognitive health, contributing to the pathogenesis of neurodegenerative conditions such as AD. Meta-analyses consistently link sleep-related issues—including inadequate or excessive sleep duration, poor sleep quality, circadian disruptions, insomnia, and obstructive sleep apnea—with an increased risk of cognitive decline and dementia.

Recent findings also emphasize the connection between the sleep-wake cycle and Aβ levels, which play an essential role in AD, as well as the influence of sleep disruption on abnormal tau protein spread. Despite these associations, interventions targeting sleep quality have shown mixed results, and there is limited evidence that improving sleep (aside from managing obstructive sleep apnea) leads to significant cognitive benefits. Nonetheless, the substantial observational evidence highlights the need to address sleep-related factors to reduce the risk of cognitive decline and dementia.

Social Connections

Enhancing social connections is crucial for older adults, who often experience social isolation due to retirement, reduced physical energy, and mobility issues. Social isolation can lead to adverse psychological outcomes such as depression and anxiety, and it is a modifiable risk factor for dementia. ⁵² Proactive measures can mitigate these effects, including fostering meaningful connections, engaging in community activities, and participating in social support networks. ⁵²

Emphasizing social engagement can boost cognitive resilience and lower the risk of dementia. ⁵³ Studies indicate that maintaining robust social networks and meaningful interactions counteracts the adverse effects of social isolation on cognitive health, improving overall well-being and quality of life. ⁵³

Q1: Are There Established Mechanisms of Action? (Yes = 2)

Positive social connections can protect cognitive health without pharmaceuticals. Evidence suggests that social isolation or loneliness increases the risk of AD in humans and mice. ⁵⁴ One study found that social isolation leads to increased Aβ and calpain activity, which removes α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors from synaptic membranes, impairing synaptic transmission. ⁵⁴ Social support is associated with higher levels of BDNF, which is neuroprotective and may reduce the risk of dementia and stroke. ⁵⁵

Another study found that frequent phone contact (2+ times/week) with family or friends lowered the odds of MCI/dementia, accounting for demographics and vascular risk factors. ⁵² Loneliness in older adults is linked to higher cortical amyloid burden. ⁵⁶ Social connectivity fosters psychological well-being and emotional stability by enhancing resilience. Chronic social stress increases inflammatory gene expression, leading to greater disease susceptibility, while positive interactions can ameliorate these stresses. ⁵⁷

Q2: Are There Intervention Studies in People That Provide Evidence of Causality/Attribution? (Yes = 3)

The quality of social connections influences the associations between social connectivity and cognitive decline. Key variables such as proximity, engagement frequency, and connection depth significantly impact the effectiveness of social interactions and overall mental health. ⁵⁸ Individuals in committed relationships often experience more profound and frequent connections compared to those relying on less intimate interactions. ⁵⁸

Data from 13 longitudinal aging studies show that highly interactive social structures, including living with others or having a trusted confidante, are linked to a reduced risk of dementia and mortality. ⁵⁸ Engaging in meaningful social interactions and maintaining close relationships can enhance cognitive health and longevity by providing regular communication, emotional support, and shared experiences. ⁵⁸

Studies in dementia care units emphasize process evaluations to understand how interventions bring about change by assessing mechanisms, outcomes, and contextual aspects. ⁵⁹ By fostering solid social connections, individuals can enhance their quality of life and potentially protect against age-related cognitive decline and mortality. Intervention studies support the positive impact of social connectivity on cognitive health.

Q3: Are There Observational Studies to Establish Generalizability to a Large Population? (A Plurality Studies). (Yes = 2)

Observational studies establish the generalizability of the relationship between social connectivity and cognitive decline across large populations. Older adults often experience profound loneliness, emphasizing the need to address their social needs through inclusive communities, intergenerational activities, and tailored support systems. ⁶⁰ Modern methods, such as tablets and electronic devices, help older adults or homebound individuals maintain connections with distant friends and family. ⁶⁰ Studies have shown positive attitudes toward using tablets and mobile applications to enhance social support for people with dementia. ⁶⁰

Regular, meaningful social interactions are vital for individuals vulnerable to cognitive decline from loneliness. ⁶¹ Strong social connections, emotional support, empathy, and companionship help lessen loneliness’s impact on cognitive health, supporting resilience and preserving cognitive function. ⁶²

Longitudinal studies in Indian society support the benefits of social networks in reducing dementia’s impact. ⁶² These findings underline the importance of meaningful social interactions in supporting cognitive health in aging populations.

Q4: Are They Measured in Decades, Lifetimes, or Generations? (Yes = 2)

Social isolation can result from factors like age-related hearing loss, which is linked to depression and cognitive decline. ⁶³ This emphasizes the multifaceted nature of hearing impairment, impacting mental health and cognitive function. ⁶³ A study involving two longitudinal cohorts followed for 10-14 years highlights the interconnectedness of loneliness, cognitive decline, and dementia. ⁶³

Holistic approaches are essential to address both auditory challenges and associated emotional and cognitive repercussions. ⁶⁴ Factors degrading social connection quality, such as limited support networks and strained relationships, negatively impact cognitive health. ⁶⁴ Proactive strategies to combat social isolation include fostering deep connections and participating in community activities. ⁶⁴

Research timelines vary: one study focused on social isolation and dementia risk over nine years among Medicare beneficiaries, another examined loneliness and dementia over six years, and a third conducted follow-up assessments over several years.^65-67

Score = 9, Grade A (Strong/decisive) ≥7

Fostering robust social connections is imperative for cognitive health and overall well-being as individuals age. By promoting meaningful interactions and community engagement, people can reduce the risks of social isolation and potentially lower the incidence of cognitive decline and dementia.

Acknowledging social isolation as a modifiable risk factor empowers individuals to prioritize social engagement, strengthen bonds, enhance resilience, and promote cognitive vitality, thereby improving overall quality of life. Integrating effective social support strategies into healthcare and community policies is essential for promoting healthier aging and enhancing quality of life across diverse populations.

Stress Management

The harmful effects of chronic stress have long been speculated to affect cognition via the hypothalamic-pituitary axis. Chronic stress affects the prefrontal cortex and hippocampus, areas of higher cognitive function. ⁶⁸ For this reason, there is interest in the management of stress to slow the onset and progression of dementia and cognitive impairment.

Q1: Are There Established Mechanisms of Action? (Yes = 2)

As mentioned above, the proposed mechanism of action by which stress and stress management affect dementia and cognitive impairment is through the Hypothalamic-Pituitary-Adrenal (HPA) axis. ⁶⁸ Research done in animals and humans denotes the effects of chronic stress through the HPA axis by glucocorticoid secretion and receptor dysregulation. ⁶⁸ These changes have been postulated to result in neurotoxicity and ultimately promoting neurocognitive decline.^68,69 Reduction of chronic stress via stress management is theorized to help curtail its impact on neurocognitive decline.

Q2: Are There Intervention Studies in People That Provide Evidence of Causality/Attribution? (Uncertain = 1)

There are inconsistencies in studies evaluating stress management’s attribution to dementia and cognitive decline. A small non-randomized trial evaluated a multimodal approach for patients with established objective cognitive decline; the interventions included stress management, nutrition, and exercise; their findings were significant for improved cognitive function after six months. ⁷⁰ The results were significant, but this interventional study didn’t examine stress management in isolation. ⁷⁰ A study looking into multimodal interventions of web-based apps vs paper format also showed that this approach improved self-reported memory failures while showing no statistically significant change in cognitive function. ⁷¹ In addition, an RCT utilizing functional MRI/questionnaires evaluated the effects of mindfulness-based stress reduction on cognitive impairment and found no significant change. ⁷² Due to the inconsistencies in the studies, it is uncertain whether stress management has casualty or attribution regarding dementia and cognitive decline.

Q3: Are There Observational Studies to Establish Generalizability to a Large Population? (A Plurality Studies). (Uncertain = 1)

Multiple observational studies explore stress and stress management’s impact on cognitive impairment and dementia, supporting generalizability. Adverse Childhood Experiences (ACEs), traumatic events, correlate with numerous adverse outcomes, from chronic diseases to psychiatric illness. ⁷³ A 2020 Behavioral Risk Factor Surveillance System survey linked ACEs with subjective cognitive decline (SCD), indicating a positive association with toxic stress. ⁷⁴

Psychological resilience, or coping with stress, has been studied concerning cognition. One study found that while perceived stress correlated with poorer cognition, psychological resilience did not buffer these effects as expected. ⁷⁵ Stress management did not lessen the negative impacts of chronic toxic stress, and cumulative stress exposure consistently showed adverse effects on cognition, with limited evidence suggesting that healthy lifestyles could moderate these effects. ⁷⁶ Other prospective cohort studies also demonstrated associations between stress and cognitive impairment. ⁷⁷ However, findings varied: while some studies indicated worsened cognition with increased stress, others found minimal effects despite psychological or stress resilience. These discrepancies complicate drawing definitive conclusions. ⁷⁷

Limitations of these studies include the inability to follow subjects over long periods and variability in outcome measures and definitions of cognitive impairment, ranging from dementia and AD to mild and subjective cognitive impairment. Consequently, the generalizability of these findings to broader populations remains uncertain.

Q4: Are They Measured in Decades, Lifetimes, or Generations? (No = 0)

When evaluating most studies’ follow-up lengths, few were measured over an extended period. For example, a prospective cohort study examined the effects of Toxic Stress (TS) and Resilience Promoting Factors (RPF). ⁷⁸ Their findings revealed that TS operates in a race and RPF-dependent manner, often overpowering protective factors that might otherwise be effective. ⁷⁸ This study’s extended 10-year duration provided ample time to observe the effects of TSTS and RPF. ⁷⁸ In contrast, many other observational and interventional studies typically lasted less than 12 months on average or were conducted as cross-sectional studies. ⁷⁸ This limited timeframe restricts the ability to establish causality definitively or to allow sufficient time for the intended outcomes to develop and manifest fully.

Score = 4, Grade C (insufficient/inconclusive)

Given the currently available studies, we have insufficient/inconclusive evidence regarding stress management as a Lifestyle Medicine intervention for dementia and cognitive impairment. While there are compelling mechanisms of action (i.e., HPA axis and negative impact on the prefrontal cortex and hippocampus), it is uncertain if the interventional studies show causality/attribution. In addition, there are some contradicting results when looking at the observational studies that would show generalizability to large populations.

Finally, given the timescale constraints of measuring the effects of stress management and its impact on dementia/cognitive impairment, a plurality is unable to be achieved. This yields inconclusive results, a “Grade C” on the HEALM approach strength of evidence. Further inquiry is needed to determine the actual effects of stress management as a form of intervention on dementia and cognitive impairment.

Avoidance of Risky Substances

Substance use has a profound impact on cognitive health in older adults, who are particularly susceptible due to age-related changes in metabolism, body composition, and cognitive function. Beyond illicit drugs and prescribed medications, alcohol and nicotine, commonly used by this demographic, can impair cognitive function, memory, and emotional regulation. For this article, alcohol use and its effect on cognitive health will be discussed in more detail.

Q1: Are There Established Mechanisms of Action? (Yes = 2)

Alcohol metabolism differs in the older population due to physiological changes, resulting in increased sensitivity to smaller amounts and a higher risk of drug interaction. Chronic heavy alcohol intake, in particular, is associated with brain atrophy, dementia, and an increased risk of severe memory impairment. ⁷⁹ At a molecular level, alcohol enhances Gamma-aminobutyric acid (GABA) activity and blocks the N-methyl-D-aspartate (NMDA) receptor. ⁸⁰ Chronic glutamate inhibition can have a toxic effect. High alcohol levels not only pose toxicity but also contribute to vitamin deficiencies (e.g., B1, B12, and folate), impacting memory and executive function. ⁸⁰ Even moderate alcohol consumption impairs memory, attention, and executive function. ⁸¹ Chronic alcohol use triggers cytokines, toll-like receptor activation, prostaglandins, inducible nitric oxide synthase (iNOS), and microglia activation, leading to neurodegeneration and neuronal loss. ⁸¹

Theories also link alcohol to dementia via Aβ plaque accumulation, which activates microglia and releases inflammatory cytokines, potentially harming brain cells.^82,83 Additionally, both human and mice studies have demonstrated the detrimental effects of alcohol use resulting in structural changes, particularly brain atrophy at critical structures associated with memory. ⁸⁴

Besides direct damage to the brain, excessive alcohol use can lead to liver damage and hepatic encephalopathy, resulting in cognitive decline. ⁸¹

Q2: Are There Intervention Studies in People That Provide Evidence of Causality/Attribution? (Yes = 3)

Alcohol use has been associated with a decrease in frontal lobe brain size.^84,85 Chronic alcohol misuse can lead to structural changes in the brain, affecting cognitive functions such as memory, decision-making, and emotional regulation. ⁸⁴ It is essential to be mindful of alcohol consumption, especially in older adults, to maintain optimal cognitive health. ⁸⁴ Chronic alcohol misuse accelerates brain aging and contributes to cognitive impairments, particularly in memory. ⁸⁵ While light to moderate alcohol use may be associated with a decreased risk of cognitive impairment and dementia, Alcohol Use Disorder (AUD) specifically increases the risk for AD. ⁸⁵

Q3: Are There Observational Studies to Establish Generalizability to a Large Population? (A Plurality Studies). (Yes = 2)

Alcohol use disorders were a major risk factor for dementia. ⁸⁶ Even moderate consumption of alcohol is associated with structural brain atrophy.^86,87 Observational studies reveal a U-shaped pattern: light to moderate alcohol use is associated with a decreased risk of cognitive impairment and dementia, while heavy alcohol use increases the risk. ⁸⁵ AUDs are preventable risk factors for all types of dementia. ⁸⁵ Reducing heavy alcohol use may be an effective strategy for dementia prevention. ⁸⁵

Q4: Are They Measured in Decades, Lifetimes, or Generations? (Yes = 2)

A prospective cohort study of Whitehall II study had 9087 initial participants with 397 cases of dementia documented at the 23-year follow-up. ⁸⁸ Alcohol consumption habits showed that there was an increased risk of dementia in alcohol abstainers and in those who consumed more than 14 units per week. ⁸⁸

The Adventist Health Study, a comprehensive research initiative examining the health behaviors and outcomes of Seventh-day Adventists, has provided critical insights into the relationship between alcohol use and cognitive decline, particularly in the older population. ⁸⁹ Findings from the study suggest that abstaining from alcohol may be associated with a reduced risk of dementia and cognitive impairment in older adults. ⁸⁹ This correlation is particularly significant given the Adventist community’s general adherence to a lifestyle free from alcohol, which may contribute to their lower incidence of cognitive decline compared to the general population. ⁸⁹ These results underscore the potential neuroprotective benefits of alcohol abstinence in aging individuals, highlighting the importance of lifestyle choices in the prevention of dementia and the maintenance of cognitive health in older individuals. ⁸⁹

Score = 9, Grade A (Strong/decisive) ≥7

Prevention is primary when it comes to maintaining brain health. By avoiding risky substances, including alcohol, we can significantly reduce the chances of developing dementia and other cognitive impairment. The use of dangerous substances is associated with developing at least mild cognitive impairment and all-cause dementia. ⁴ Avoiding risky substances is necessary for preserving and optimizing cognitive health. See Table 2 for detailed information on the Strength-of-Recommendation Taxonomy (SORT) evidence rating and the HEALM framework, covering all six pillars of Lifestyle Medicine and their impact on dementia and cognitive decline.

Table 2.

Strength-of-Recommendation Taxonomy (SORT) of the Six Pillars of Lifestyle Medicine on Dementia and Cognitive Decline.

Clinical Recommendations	Evidence Rating	The HEALM Framework	Comments
The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, alongside a broader focus on modifiable lifestyle factors, reduces cognitive decline and promotes long-term cognitive health. Implementing a MIND diet, which includes a high intake of vegetables, berries, nuts, whole grains, olive oil, and beans while reducing meat, sugars, and saturated fats, is strongly recommended due to high-quality evidence from randomized controlled trials demonstrating its efficacy in reducing dementia risk.	A	A	Meta-analysis, RCTs. Score nine on HEALM strength of evidence approach.
Regular physical exercise is strongly recommended to enhance cognitive function and reduce the risk of cognitive decline and dementia, supported by robust evidence from intervention and observational studies. Participating in at least 150 minutes of moderate-intensity physical exercise per week is strongly recommended to enhance cognitive function and reduce the risk of cognitive decline and dementia, supported by robust evidence from intervention and observational studies.	A	A	Meta-analysis, RCTs. Score nine on HEALM strength of evidence approach.
Ensuring restorative sleep through managing sleep duration, quality, and circadian rhythms is strongly recommended for preventing dementia and cognitive impairment, supported by robust observational and meta-analytic evidence. Prioritizing restorative sleep through managing sleep duration, quality, and circadian rhythms is strongly recommended for preventing dementia and cognitive impairment, supported by robust evidence from observational and intervention studies demonstrating its significant impact on cognitive health.	A	A	Meta-analysis, RCTs, cross-sectional studies, prospective studies. Score eight on HEALM strength of evidence approach.
Engaging in regular, meaningful social interactions and maintaining strong social connections is strongly recommended to prevent cognitive decline and dementia, supported by studies demonstrating its significant impact on cognitive health.	A	C	Longitudinal population-based study, meta-analysis. Score nine on HEALM strength of evidence approach.
The evidence is currently insufficient to recommend stress management as an effective standalone intervention for preventing dementia and cognitive impairment, though its potential benefits warrant further investigation.	C	C	RCTs, cross-sectional studies, prospective studies. Score four on HEALM strength of evidence approach.
Avoiding risky substances, including heavy alcohol use, is strongly recommended to preserve and optimize cognitive health, supported by evidence from observational and intervention studies demonstrating the significant impact of alcohol use on cognitive decline and dementia risk. Older adults should avoid heavy alcohol use and consider moderation or abstinence to reduce the risk of cognitive impairment and dementia, supported by strong evidence from observational and intervention studies demonstrating significant neuroprotective benefits.	A	A	Longitudinal cohort studies, meta-analysis. Score nine on HEALM strength of evidence approach

A = consistent, good-quality patient-oriented evidence ^a ; B = inconsistent or limited-quality patient-oriented evidence ^a ; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. ^b

^aPatient-oriented evidence measures outcomes that matter to patients: morbidity, mortality, symptom improvement, cost reduction, and quality of life.

^bDisease-oriented evidence measures intermediate, physiologic, or surrogate endpoints that may or may not reflect improvements in patient outcomes (e.g., blood pressure, blood chemistry, physiologic function, pathologic findings). For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

Discussion

This comprehensive review highlights the vital role of lifestyle interventions in promoting cognitive health and reducing the risk of dementia. Utilizing the HEALM framework, we have analyzed extensive evidence supporting key lifestyle factors—such as plant-based nutrition, physical activity, restorative sleep, social connections, stress management, and the avoidance of harmful substances—as effective in enhancing cognitive function and potentially slowing cognitive decline. Plant-based diets, rich in antioxidants and anti-inflammatory compounds, are associated with better brain health. Physical activity modulates neurobiological pathways essential for maintaining cognitive vitality. Quality sleep aids memory consolidation, while effective management of chronic stress may help mitigate its negative effects on cognitive regions of the brain. Additionally, social engagement protects against cognitive decline, and avoiding harmful substances like alcohol and nicotine is crucial for maintaining cognitive health.

However, it is essential to acknowledge that while highly effective in addressing these various health domains, lifestyle medicine often overlooks the intricate interactions among these components. Interventions such as those for heart disease reversal and diabetes prevention typically employ multiple strategies simultaneously, making it difficult to isolate the effects of any single intervention. This complexity suggests that both the individual elements and the overall approach contribute to positive outcomes, emphasizing the importance of recognizing this nuance when evaluating the effectiveness of lifestyle interventions.

This is well illustrated in studies such as the Stanford Five-City Project, an extensive community-wide health education initiative aimed at cardiovascular disease prevention. ⁹⁰ The project hypothesized that a 20% reduction in cardiovascular risk factors through a multifaceted intervention would result in significant declines in cardiovascular events in the treatment communities compared to control communities. ⁹⁰ Similarly, the North Karelia Project initially focused on cardiovascular disease but has expanded its scope to address cognitive impairment and dementia. ⁹¹ Its legacy continues in studies like CAIDE and FINGER, which have identified modifiable risk factors for dementia, including hypertension, obesity, diabetes, and depression. ⁹¹ The FINGER study, in particular, demonstrates that a multidomain lifestyle-based intervention can effectively prevent cognitive impairment. ⁹¹ These findings reinforce the importance of early prevention through healthier lifestyles and better risk factor management. Ongoing studies aim to build on this approach and develop evidence-based prevention programs to reduce dementia prevalence globally. ⁹¹

Conclusion

Emphasizing the significance of lifestyle interventions is essential for preserving cognitive health and addressing the growing burden of dementia. While substantial evidence supports the impact of various lifestyle factors, gaps in knowledge remain, particularly in stress management interventions, where conclusive evidence is indefinite. Furthermore, the interplay among lifestyle domains should not be overlooked. For example, avoiding excess alcohol can improve sleep, which in turn enhances stress tolerance, creating a cycle that further supports cognitive health. Similarly, exercise can mitigate stress and improve sleep through both direct and indirect pathways, while better sleep can increase energy levels, leading to more physical activity.

Integrating these evidence-based lifestyle interventions into clinical practice and public health policies can empower individuals to enhance their cognitive resilience and overall well-being. By recognizing how these lifestyle factors interact with one another, we can better address the growing burden of dementia and cognitive decline, promote healthier aging, and improve quality of life across diverse populations.

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ORCID iDs

Ecler Jaqua https://orcid.org/0000-0001-6694-1485

Mai-Linh Tran https://orcid.org/0009-0004-8560-0087

Monica Gupta https://orcid.org/0000-0003-0514-9739