Below the Neck, Above the Neck: How Cardiometabolic Health Shapes the Brain
Below the Neck, Above the Neck
How Cardiometabolic Health Shapes the Brain — and How Brain Health Shapes the Body
Abstract / Summary
Heart disease, diabetes, obesity, depression, anxiety, migraines, dementia, and neurodegenerative diseases are usually treated as separate problems by different medical specialties. However, growing evidence shows they are deeply connected through shared biological pathways involving insulin resistance, vascular dysfunction, inflammation, mitochondrial failure, stress hormones, sleep disruption, and the gut microbiome. This article explores how cardiometabolic disease affects brain function and how psychiatric and neurologic disorders, in turn, worsen metabolic health, forming a self-reinforcing brain-body-loop. We review evolutionary biology, modern lifestyle mismatch, genetics, and clinical research linking insulin resistance to cognitive decline, mood disorders, migraines, seizures, Parkinson’s disease, and multiple sclerosis. Finally, we explain why lifestyle and metabolic therapies are not “soft medicine,” but foundational neurovascular and neuropsychiatric prevention strategies.
The False Divide Between Body Disease and Brain Disease
Most people think of heart disease, diabetes, and weight problems as “body” issues, while depression, anxiety, ADHD, bipolar disorder, cognitive decline, migraines, and dementia are viewed as neurologic or psychiatric problems. As a result, they are treated in different offices, by different specialists, and often with completely different strategies.
But biologically, they are deeply connected.
The same metabolic and vascular systems that determine heart disease risk also shape how the brain feels, thinks, and ages. And brain and mental health disorders feed back into metabolic health through stress hormones, sleep disruption, inflammation, and behavior. This is not a one-way street. It is a loop, below the neck and above the neck influencing each other continuously.
One Observation, Two Medical Disciplines
For years, clinicians have observed, and research has increasingly confirmed, a tight and clinically meaningful link between insulin resistance and diseases of the brain, including dementia, chronic brain fog, mood disorders, Parkinson’s disease, and stroke [1–4]. Many patients do not have obvious diabetes or severely elevated blood sugar. Instead, they carry quieter fingerprints of metabolic dysfunction: central weight gain, low HDL, elevated triglycerides, rising blood pressure, chronic inflammation, and often significant coronary calcium on imaging. Their arteries are telling a story their glucose is not.
This is not an isolated observation. Colleagues in psychiatry, including Dr. Roger McIntyre at the University of Toronto, have described this same relationship from the opposite clinical direction, how mood disorders, attention disorders, and their treatments increase cardiometabolic risk and reduce life expectancy, largely through cardiovascular disease [5–7]. We have discussed this convergence directly: psychiatry approaching from above the neck looking down, and cardiometabolic medicine approaching from below the neck looking up. Different starting points, same conclusion, these are not separate systems.
Fundamental Cardiometabolic Drivers of Brain Health
Across many neurologic and psychiatric conditions, the same physiologic drivers repeatedly appear: insulin resistance and hyperinsulinemia, endothelial and microvascular dysfunction, chronic inflammation, mitochondrial stress, autonomic nervous system imbalance, sleep disruption, and gut microbiome dysbiosis. These are not isolated abnormalities. They are interconnected features of an unhealthy metabolic terrain.
When this terrain is impaired, blood flow to the brain becomes less efficient, immune signaling becomes more aggressive, and energy production inside neurons becomes less reliable. The brain is uniquely vulnerable to these changes because of its high energy demands and limited ability to store fuel.
Why the Brain Is Often the First to Complain... and the Last to Be Diagnosed
The brain uses roughly 20% of the body’s energy at rest and cannot store fuel. Even small disruptions in oxygen delivery, glucose transport, or mitochondrial function can rapidly affect mood, attention, memory, and sleep. This is why symptoms like brain fog, fatigue, irritability, poor concentration, and anxiety often appear years before diagnoses such as dementia, Parkinson’s disease, multiple sclerosis, or stroke are made.
Those diagnoses are usually late manifestations of long-standing metabolic, vascular, and inflammatory stress. In this sense, neuropsychiatric symptoms are often early warning signs of cardiometabolic disease, not separate problems.
Dementia, Insulin Resistance, and Energy Starvation of the Brain
In dementia and cognitive decline, reduced cerebral blood flow, chronic inflammation, and impaired insulin signaling interfere with learning and memory. But an equally important and often overlooked problem is loss of metabolic flexibility, the ability of the brain to switch between glucose and ketones for fuel.
Under healthy conditions, neurons can use both glucose and ketones. This matters because neurons cannot store energy. In insulin resistance, two major problems occur simultaneously: glucose transport into neurons becomes impaired, and high insulin suppresses liver ketone production. The brain becomes trapped without reliable access to either fuel source.
This creates a state of chronic energy starvation, particularly harmful to the hippocampus, the brain’s memory center and one of the first regions affected in Alzheimer’s disease [8–10]. After the ApoE4 genotype, elevated insulin levels and insulin resistance are among the strongest predictors of future Alzheimer’s risk [11–13]. This helps explain why Alzheimer’s disease is increasingly described as a metabolic brain disorder rather than simply a protein-accumulation disease.
Evolution, Baby Fat, and Why the Brain Loves Ketones
Humans are the only land mammals whose babies are born with very high body fat and relatively little muscle. Other mammals are born ready to stand and move. Human babies are born “soft,” and we even celebrate that "baby fat" but there is an evolutionary reason for it. That fat supports rapid brain growth.
Human breast milk is uniquely high in fat, and newborns naturally spend much of their time in mild ketosis. Ketones are efficient, clean-burning fuels for neurons and are critical for building brain tissue during early development [14–16]. From the very beginning of life, the human brain is designed to thrive on fat-derived fuels.
Adult brains still benefit from ketone access. Ketones improve mitochondrial efficiency, reduce oxidative stress, and stabilize neural signaling. But insulin resistance shuts this system down by blocking ketone production and impairing glucose uptake at the same time.
Seizures: The Original Proof That Brain Fuel Matters
Long before ketogenic diets were discussed for weight loss or metabolic health, they were used as medical therapy for epilepsy. Ketogenic therapy has been part of neurologic treatment for nearly a century, especially in children with drug-resistant seizures [17–19].
Seizures occur when groups of neurons fire in an uncontrolled, synchronized way. This instability is strongly influenced by how well brain cells regulate energy and neurotransmitter balance. Ketones provide a more stable fuel source, improve mitochondrial function, and reduce oxidative stress, raising the brain’s threshold for abnormal firing.
Clinical studies show that ketogenic diets can significantly reduce seizure frequency and, in some patients, lead to complete seizure control when medications alone are insufficient [17–19]. This is powerful evidence that altering brain fuel metabolism can directly change neurologic disease expression, not just suppress symptoms.
Epilepsy demonstrates clearly that when we change the brain’s fuel, we can change the disease.
Mood Disorders, Brain Fog, and Psychiatric Disease
Depression, anxiety, ADHD, and bipolar disorder are not just neurotransmitter problems. They are strongly linked to inflammation, insulin resistance, circadian disruption, mitochondrial dysfunction, and vascular health [5,20–22].
Inflammatory cytokines alter serotonin and dopamine signaling. Cortisol disrupts hippocampal function. Insulin resistance reduces neuronal energy availability. This may help explain why many patients experience partial or short-lived responses to psychiatric medications when metabolic and inflammatory drivers remain unaddressed.
This metabolic vulnerability also helps explain why depression in midlife is associated with higher dementia risk later in life, both may reflect shared metabolic and inflammatory pathways affecting the brain over decades.
Migraines as Neurovascular Energy Disorders
Migraines are often treated with symptom-targeting medications, but many patients have underlying metabolic and vascular instability. Blood sugar swings, insulin resistance, endothelial dysfunction, and mitochondrial stress lower the brain’s threshold for triggering migraine attacks [23]. Even when fasting glucose and A1c are normal, people with migraine headaches are much more likely to show insulin resistance when tested with an oral glucose tolerance test that includes insulin measurements. This abnormal insulin response is not seen with other common headache types, suggesting that migraine is specifically linked to disordered metabolic and vascular regulation, not just pain sensitivity.
Ketogenic and low-glycemic diets have been shown to reduce migraine frequency and severity, likely by stabilizing brain energy supply and reducing inflammatory signaling [24]. Yet metabolic therapy remains underutilized compared with pharmaceutical approaches that do not address underlying fuel biology.
Neurodegeneration: Parkinson’s Disease and Multiple Sclerosis
In Parkinson’s disease, dopamine-producing neurons are highly dependent on mitochondrial energy production. Insulin resistance and chronic inflammation increase oxidative stress and impair mitochondrial function, accelerating vulnerability to degeneration [2,25]. Notably, mood and anxiety symptoms often precede motor symptoms, suggesting early neuropsychiatric manifestations of metabolic brain stress. In addition, very high coronary calcium scores have been identified in many patients with Parkinson’s disease despite non-obstructive coronary anatomy, indicating severe underlying cardiometabolic dysfunction even when classic cardiac symptoms are absent.
In multiple sclerosis, immune attacks on myelin are influenced by gut microbiome composition, metabolic health, and inflammatory tone. Obesity and insulin resistance are associated with higher MS risk and worse disease progression [26–28].
Different diagnoses. Same terrain.
The Gut–Brain–Immune Highway
The gut is a major immune and metabolic control center. When microbiome balance is disrupted and intestinal permeability increases, inflammatory molecules enter the bloodstream and activate immune responses that reach the brain [29–31].
This gut-driven inflammation contributes to depression, anxiety, brain fog, migraines, Parkinson’s disease progression, and multiple sclerosis activity. Metabolic disease worsens gut barrier function, and gut inflammation worsens metabolic control, creating yet another feedback loop.
Stress, Cortisol, Sleep, and the Autonomic Nervous System
Chronic stress activates the sympathetic nervous system and raises cortisol, increasing blood pressure, insulin resistance, visceral fat, and inflammation. At the same time, it disrupts sleep, impairs memory formation, increases anxiety, and lowers emotional resilience.
Sleep is when the brain clears metabolic waste and restores neurotransmitter balance. Sleep fragmentation and short sleep duration are strongly associated with insulin resistance and accelerated neurodegeneration [32–34].
Stress physiology is not psychological alone, it is metabolic and vascular.
BDNF: Fertilizer for the Brain
Exercise raises levels of brain-derived neurotrophic factor (BDNF), a protein that acts like fertilizer for the brain. BDNF supports neuron growth, synaptic plasticity, learning, and recovery from stress [35–37].
Exercise is one of the few proven ways to increase BDNF. Low BDNF levels are associated with depression, insulin resistance, cognitive decline, and neurodegenerative disease. When BDNF is high, the brain is more adaptable and resilient.
This helps explain why many high-performing executives start their day with exercise, not just for fitness, but because it improves cognitive clarity and emotional regulation during demanding work hours.
Genetics Loads the Gun, Metabolism Pulls the Trigger
Genes such as ApoE4 increase vulnerability to Alzheimer’s disease, but genes are not destiny. Metabolic health determines whether that risk is activated, delayed, or accelerated [11–13].
Lifestyle, nutrition, stress, sleep, muscle mass, gut health, and environmental exposures shape gene expression through epigenetic mechanisms. In this way, daily behavior directly influences long-term neurologic risk.
Why Traditional Medicine Treats Brain Disease With Pills Instead of Fuel
Modern neurology and psychiatry often focus on downstream pathology, neurotransmitters, plaques, tangles, and pain pathways. Yet decades of Alzheimer’s drug trials targeting amyloid and tau have largely failed to produce meaningful clinical improvements, even when biomarkers improve [38–40].
Meanwhile, metabolic therapies continue to show signals of benefit. A large Veterans Affairs study found that patients with diabetes treated with PPAR-γ agonists (TZDs such as pioglitazone) had significantly lower dementia risk compared with other diabetes drugs, while sulfonylureas were associated with higher risk, effects not explained by glucose alone [41]. PPAR-γ activation improves insulin sensitivity, reduces inflammation, and supports mitochondrial function, again pointing to terrain rather than sugar alone.
Yet lifestyle and metabolic strategies remain underused because they require education, coaching, and long-term engagement rather than prescriptions alone. Medications are often faster and easier to deploy and can provide short-term symptom relief, but durable improvement requires foundational care that restores metabolic health, vascular function, and brain energy balance.
Why Lifestyle Is Neurovascular and Neuropsychiatric Medicine
Lifestyle is not soft medicine. It is neurovascular and neuropsychiatric medicine.
Muscle improves insulin sensitivity and releases anti-inflammatory myokines. Exercise increases mitochondrial capacity and BDNF. Nutrition stabilizes insulin and supports beneficial gut bacteria. Sleep restores brain clearance systems. Stress regulation lowers inflammatory signaling. Social connection reduces physiologic stress responses.
These are not optional add-ons. They directly shape disease risk in cardiology, neurology, and psychiatry alike.
Reconnecting the Head to the Body: One Connected System
Across heart disease, diabetes, depression, brain fog, migraines, seizures, and neurodegenerative disorders, the same drivers appear: insulin resistance, inflammation, impaired blood flow, mitochondrial dysfunction, gut dysbiosis, stress, and sleep disruption.
The brain often complains first. The diagnoses come later.
This is why treating neurologic and psychiatric symptoms without restoring metabolic flexibility often leads to partial relief at best.
Or said simply:
When we treat brain disorders without restoring metabolic flexibility, we manage symptoms above the neck while the metabolic fire below the neck keeps fueling the disease.
Below the neck... Above the neck... One connected system.
If you’ve ever been told “your labs look fine” while your gut says something isn’t, or your scan shows calcium that doesn’t square with a “normal” glucose, you’re not imagining things.
"The brain hears the whispers of the body long before glucose shouts."
Author: Dr John Sciales
Director, CardioCore Metabolic Wellness Center
"Getting to the Core- where being Healthy is Not an Accident"
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Wang CP, et al. Diabetes meds and dementia risk. BMJ Open Diabetes Res Care. 2022.e Metabolic Wellness Center, we align care with these realities. Our approach starts with insulin-centric assessment, adds objective vascular imaging when indicated, and deploys a personalized plan that integrates nutrition, resistance training, sleep/circadian hygiene, and appropriate therapeutics. The goal is not simply to lower a number—it’s to brighten the metabolic sun so every organ-planet holds a stable, healthy orbit.
