PLMI Blog

Cognitive decline and dementia, particularly Alzheimer’s disease (AD), have become some of the most prevalent health conditions, with an estimated 6.9 million Americans 65 years of age and older living with AD (1). While genetics play a role in the etiology of these conditions, lifestyle factors also play a substantial role in how genes become expressed. As lifestyle factors also influence systemic health, they are a significant piece of the puzzle regarding neurodegenerative disease.

Growing evidence underscores the influence lifestyle factors have in supporting and modulating neurological health while mitigating the effects of neurodegenerative conditions, and potentially even reversing cognitive decline. Lifestyle factors that address the interconnected systems that influence the pathophysiology of these conditions yield the strongest results.

Underlying Factors That Impede Neuronal Health

Research has revealed the role of inflammation in neurodegenerative conditions. Elevated levels of inflammatory markers (CRP, homocysteine, tumor necrosis factor, and omega-6 to omega-3 ratio) have been associated with AD pathology. Alterations in immune system markers have also been associated with AD, including immunoglobulins and lymphocyte subsets. Further systemic dysregulation includes gut microbiome imbalances and recurring infections—all of which impede neuronal function and metabolism and induce neuroinflammation. Neuroinflammation disrupts synthesis of serotonin, GABA, dopamine, and melatonin, as well as neurotrophic activity—including neural signaling and neuroplasticity.

A growing body of research also demonstrates that metabolic dysfunction plays a central role in AD and cognitive health and is compounded by systemic and oxidative stress, inflammation, neuroinflammation, and toxins (2). These processes are shown to impede brain metabolism and mitochondrial function. Emerging findings also highlight comorbidities between metabolic disorders and AD. This is encouraging, as it speaks to the underlying role metabolic dysregulation has in influencing neuronal health.

Research is showing that the most impactful lifestyle factors in neurodegenerative conditions are those that modulate and support systemic imbalances, highlighting the roles of nutrition,  exercise, sleep, engagement, and stress modulation as foundational pillars of brain health—with evidence supporting their efficacy in combating cognitive decline.

Energetic Support – Energetic factors, including promoting cerebral blood flow and improving oxygen saturation and mitochondrial function, are essential to neuronal health and are often indicators of metabolism in the body and brain. Supporting metabolic dysregulation, including insulin resistance and lipid profiles, is also significant, as is reducing toxicant exposure (2).

Trophic Support – Cellular health is shown to be greatly impeded in neurodegenerative conditions. Nutrients and lifestyle factors that increase brain-derived neurotrophic factor (BDNF – a protein that promotes survival and growth of neurons and improves mitochondrial function and hormonal balance, thereby influencing brain health) are shown to be impactful. Reducing inflammation and toxic burden, improving detox capacities, and other impeded metabolic processes, such as methylation, are further recommended for improved cellular health (2).

TARGETED LIFESTYLE INTERVENTIONS

Nutrition: Foundational for Brain Health

A nutrient-dense, anti-inflammatory diet is essential for reducing systemic inflammation and supporting overall brain function. While diet is highly bioindividual, research suggests the ketogenic, Mediterranean, and MIND diets may all improve systemic metabolic dysfunction and neuroinflammation—underlying neurodegenerative health conditions. Notably, the keto diet is suggested to improve brain metabolism, insulin sensitivity, and the brain’s ability to utilize ketones as an efficient energy source, all critical in optimizing cognitive function (3).

Omega-3s – Research shows that omega-3 fatty acids play a role in reducing neuroinflammation and oxidative stress, both of which are contributors to AD and other neurodegenerative conditions (3). Docosahexaenoic acid (DHA), found in fatty fish, is critical for reducing brain inflammation, supporting neuroprotection, and ensuring proper neurotransmission.

B Vitamins – B vitamins, including B6, B12, and folate, are vital for neurotransmitter synthesis, methylation processes, and the overall maintenance of brain health. Deficiencies in these vitamins are linked to poor cognitive function and mood disorders. Low levels of vitamin B12 have been shown to exacerbate cognitive decline, while folate plays a role in the synthesis of serotonin, which helps regulate mood and cognition.

Antioxidant-Rich Foods – Fruits and vegetables are rich in antioxidants, which help to combat oxidative stress—a major contributor to neuronal damage. Berries, leafy greens, and cruciferous vegetables help neutralize free radicals, thus protecting brain cells from oxidative damage. Polyphenols (dark chocolate, green tea, and turmeric) also have neuroprotective effects, as they support the clearance of amyloid plaques and reduce inflammation in the brain.

Anti-Inflammatory Foods – Chronic inflammation is a hallmark of many neurodegenerative diseases, including AD. An anti-inflammatory diet that emphasizes omega-3 fatty acids, polyphenols, and low-glycemic foods can help modulate inflammatory pathways in the brain, as well as support BDNF. Avoiding refined carbohydrates, processed foods, and sugar is essential, as these can contribute to dysbiosis and insulin resistance–both of which are linked to cognitive decline.

Ketosis and IF – Specific eating patterns have emerged as beneficial for neurological health by supporting these underlying systemic pathways. Ketosis, a metabolic state induced by the ketone diet, helps to restore the body’s ability to efficiently shift between glucose and ketone utilization. This shift in the body’s primary energy source has been found to support brain function by promoting metabolic flexibility and insulin sensitivity. The ketogenic diet has also been demonstrated to reduce systemic and neuroinflammation, modulate gut microbiome balance, and support mitochondrial function, improving cognitive performance in individuals with mild cognitive impairment (MCI) or early AD (3).

Similarly, intermittent fasting (IF) has shown the potential to improve cognitive function by enhancing autophagy, a cellular process that clears damaged cells and supports neuroplasticity (4).

The Role of the Microbiome

Research has shown that the gut microbiome plays a significant role in modulating brain function through its influence on systemic metabolism, detoxification, mitochondrial function, inflammation, neurotransmitter production, and immune regulation. Dysbiosis has been linked to systemic inflammation, oxidative stress, and neuroinflammation, all of which contribute to cognitive decline (5). A diet rich in probiotics, fiber, and fermented foods can help promote gut health, reduce inflammation, and enhance brain function. While nutrition plays a role, lifestyle factors also influence the state of the microbiome, including stress, movement, and sleep.

Exercise: Enhancing Brain Plasticity & Cerebral Blood Flow

Exercise supports synaptic structure and function in various brain regions that support neuroplasticity, in addition to modulating glial activation and angiogenesis—systems further implicated in promoting neuroplasticity. Exercise also improves cerebral blood flow, which is essential for delivering oxygen and nutrients to brain cells. Enhanced blood flow helps support cognitive processes, including memory consolidation and information processing. Exercise also attenuates neurodegeneration by enhancing clearance of Amyloid β protein (Aβ) (6).

Exercise & BDNF – Exercise has anti-inflammatory effects, reducing systemic and neuroinflammation that contribute to cognitive decline. Studies have shown that regular physical activity can reduce markers of inflammation. The combination of reduced inflammation and improved blood flow helps optimize brain health.

Exercise has also been shown to stimulate the production of BDNF while reducing inflammation (7). Higher levels of BDNF are associated with improved cognitive function, greater neuroplasticity, and protection against neurodegeneration (8). A 2023 study demonstrated that aerobic exercise increased plasma levels of BDNF while also enhancing synaptic plasticity, spatial memory, and motor activity in those with AD.

Both aerobic exercise and strength training have been shown to increase BDNF levels and improve hippocampal volume, a key region involved in memory and learning. Exercise has also been suggested to enhance sleep and ketosis by increasing BDNF (2). Moderate-intensity exercise has been shown to inhibit inflammatory markers, including IFN-γ, IL-1β, IL-6, CRP, TNF-α, and NF-κB, which have been implicated in neurodegenerative diseases (9). This is particularly important for mitigating the effects of metabolic conditions, such as obesity, which have shared pathophysiological mechanisms with neurodegenerative diseases (10).

Reducing Stress

Cortisol is released in response to stress and can be neurotoxic in high amounts, especially when produced over prolonged periods. Chronic stress has been shown to impair memory, reduce hippocampal volume, and accelerate brain aging (12). Stress may also impede digestion and sleep, important functions for brain health.

Modulating stress through mindfulness, yoga, and other relaxation techniques has been linked to reduced cortisol levels and improved emotional regulation, both of which are essential for brain health (13). These mind-body interventions are particularly important in counteracting the neurotoxic effects of chronic stress, which have been shown to accelerate cognitive decline and reduce hippocampal volume. Meditation has been linked to increased hippocampal gray matter volume, suggesting that stress reduction can directly impact brain structure and function (14).

Sleep: Detox for the Body & Brain

Sleep is a foundational pillar for health—body and mind. Quality sleep promotes activation of the glymphatic and lymphatic systems—helping to rid the brain and body of harmful toxins and metabolic waste. Sleep is also essential for governing nearly all systems of the body, including metabolic, GI, hormonal, and immune systems—all of which influence brain health. Sufficient sleep also helps to reduce oxidative stress and inflammation while also flushing out  Aβ – associated with AD (2).

Social Connections

Social interaction is essential for maintaining cognitive function. Isolation and loneliness have been shown to accelerate cognitive decline, while regular social engagement helps build cognitive reserve, which provides a buffer against neurodegeneration (14). The relationship between loneliness, social isolation, and mental health outcomes is suggested to be bidirectional, further underscoring the importance of social connection.

Cognitive Engagement

Evidence suggests that cognitive exercises can support neuroplasticity. Engaging in mentally stimulating activities—including learning new skills, solving puzzles, and playing memory-enhancing games—helps promote neuroplasticity and supports cognitive function.

Lifelong learning and maintaining social connections help strengthen neural pathways, which may delay the onset of dementia or AD.

Yoga, biofeedback, or vagus nerve stimulation (VNS) may be beneficial for improving brain health by enhancing vagal tone and heart-rate variability (HRV), which support cognitive function through a number of interconnected mechanisms. VNS has been suggested as a treatment for dementia–associated memory impairments in light of these findings (15).

Multifaceted Approach to Brain Health

For optimal brain health, a multidisciplinary approach that encompasses nutrition, exercise, sleep, stress reduction, learning, and social engagement is foundational, as this perspective integrates the science between the body–mind interrelationship, which has a profound impact on the etiology of neurodegenerative conditions.

Join us on March 4th from 5-7 PM PST for a pivotal event,  Reversing Cognitive Decline at Scale, hosted by Dr. Jeffrey Bland, featuring Dr. Dale Bredesen’s root-cause approach to reversing cognitive decline focusing on the underlying pathophysiological mechanisms driving conditions such as AD, and Dr. Kristine Burke’s strategies for scaling brain health interventions. This event offers novel, cutting-edge insights into personalized medicine and the prevention and treatment of neurodegenerative conditions.

References:

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