“Mens Sana in Corpore Sano”: How Metabolic Syndrome Impacts Brain Health

The Latin phrase “mens sana in corpore sano,” meaning “a healthy mind in a healthy body,” was first coined by the Roman poet Juvenal in his tenth satire. This timeless idea underscores the importance of balancing mental and physical health for a fulfilling life. In stark present contrast, metabolic syndrome is becoming a widespread public health problem.

Metabolic syndrome is often caused by an unbalanced diet combined with too little physical inactivity. It is a collection of metabolic disorders that can lead to neurocognitive dysfunction by triggering inflammatory mediators, disrupting brain metabolism and impairing cognitive function. In addition to its direct effects on brain tissue, metabolic syndrome can also cause indirect damage.

For example, evidence shows that a sedentary lifestyle reduces oxygenation and blood flow, leading to long-term neural damage. To address these issues, both preventive and therapeutic cognitive-behavioural interventions are designed to facilitate healthy lifestyle changes and improve brain function, thereby enhancing overall quality of life.

How Does The Brain Change In Metabolic Syndrome?

Metabolic Syndrome (MetS) constitutes a significant contributor to illness and mortality. It hence represents a significant threat to public health. This condition is closely linked to an increased risk of non-communicable diseases (NCDs) such as cardiovascular disease and type 2 diabetes. Beyond its serious health consequences, MetS diminishes the quality of life and places a growing economic burden on healthcare systems (1).

An emerging concern is the association between MetS and neurocognitive dysfunctions, which pose a significant challenge (2, 3). In this context, certain molecules mediating communication between cells appear to be key players in pathways that trigger metabolic inflammation and microvascular disorders. This could lead to damage brain white matter and a decline in cognitive function (4).

Furthermore, insulin resistance – a critical component of MetS – can lead to variations in blood glucose levels and elevated serum insulin. The impairment of insulin signalling in the brain, coupled with oxidative stress, can lead to biochemical modification, specifically glycation, of brain tissue and from there, subsequent brain inflammation (5). In addition, high glucose levels in the brain have been linked to cognitive impairments, including dementia. Moreover, well-known contributors to MetS like obesity and hypertension are considered risk factors both for dementia and severe brain degeneration (6).

Controlling MetS can slow the degeneration of both white and grey matter in the brain (7, 8). In addition to its role in diabetes and cerebrovascular disorders, MetS has also been identified as a risk factor for the progression of Alzheimer’s disease (9). MetS can accelerate the onset of cerebral small vessel dysfunctions causing structural and functional changes in blood vessels, leading to mild bleeding, white matter damage and brain atrophy (10), the latter most often in deep white matter areas, such as the right frontal lobe (5).

MetS can also have an indirect impact on the brain. A sedentary lifestyle is a key risk factor, as inactivity leads to reduced oxygenation and circulation, which can cause long-term neural damage. A change in lifestyle and promotion of physical activity can lead to a notable enhancement in the oxygenation of the brain, thus improving its function overall.

Shedding Light On Cognitive Impairment

Some studies have indicated a reduction in both attention and neuromuscular connections in elderly patients with MetS when performing cognitive tasks, particularly those associated with the parietal and occipital lobes (11, 12). Based on the results of numerous studies investigating the impact of MetS on brain structure and cognitive ability (7), it can be concluded that obesity, hypertension and hyperglycaemia have the greatest impact on reducing cognitive performance and ability (5, 13).

A decline in cognitive function associated with MetS is characterised by the following symptoms: reduced decision-making ability, reduced memory function and a decline in the reward system (14). It should be noted that MetS is not the only cause of impaired brain metabolism and the resulting cognitive and structural changes. At present, there is a growing focus on metabolic disorders among those studying metabolic diseases. Furthermore, the high prevalence of MetS and diabetes mellitus, coupled with the slowing of metabolism in all organs – including the brain – has led to an increased focus on MetS.

Brain metabolism is known to play a major role in causing certain neurological diseases, such as Alzheimer’s (15-17). This is due to hypometabolism – a condition where the brain uses less energy than normal – which promotes the buildup of a protein called “amyloid-beta” (Aβ) in the brain (18). Normally, this protein is cleared away but when it accumulates it can form clumps or plaques, that interfere with how brain cells communicate and can cause brain cell damage. Additionally, proton magnetic resonance spectroscopy has revealed alterations in metabolite concentration. A significant correlation has been identified between cognitive decline and neurometabolic disorders in various areas of the brain, including multiple sclerosis (19), brain tumours (20, 21), epilepsy (22, 23), Alzheimer’s disease (24-26) and dementia (27).

It has been established that the majority of metabolic diseases affecting the brain result in structural changes to neurons, which can lead to a decline in cognitive abilities. Some studies have demonstrated that patients with obesity exhibit a notable reduction in grey matter volume in various regions of the brain, including the cerebellum and thalamus, while also displaying an increase in grey matter volume in the pallidum and hippocampus (28-30).

Neurocognitive Approaches

Scientists are investigating the potential of neurocognitive interventions – which are techniques or treatments that target the brain’s functioning – to facilitate healthy behaviours or reduce harmful ones in patients with MetS. A study by researcher Garcia-Silva and colleagues evaluated the efficacy of 48 cognitive behavioural interventions in volunteers with MetS (31). These included techniques for effective refusal, anger control and appetite control. Following a period of three to six months, biochemical indices and Body Mass Index (BMI) were reassessed, revealing significant changes in these indices. The primary outcome resulting from the interventions was the ability of individuals to adhere to a diet for metabolic syndrome (31).

It has been proven that integrating cognitive interventions with other strategies, such as promoting physical activity, can result in sustained changes in children’s behaviour, habits and lifestyle. Furthermore, researchers noted a significant increase in grey matter volume in the cerebellum and total brain volume in patients with obesity when following such a holistic intervention, in comparison to healthy children (33).

The mechanisms underlying the effects of cognitive interventions have also been evaluated. A study by Shigaeff and collaborators on a cohort of adult volunteers with MetS revealed a significant increase in grey matter volume and total brain mass via a modification of food choices and dietary behaviours (11). In addition, a recent meta-analysis has also demonstrated that cognitive therapy significantly reduced binge-eating episodes and abstinence from binge-eating (34). In any case, there are encouraging reasons to see promise in neurocognitive interventions promoting structural changes in the brain—an opportunity that should be further tapped into.

Best Ways Of Designing Effective Interventions

To design effective interventions it is important to look at the behaviours associated with metabolic syndrome from different perspectives. Firstly, it is essential to address the behaviours associated with MetS, including high-risk ones such as unhealthy nutritional habits and sedentary lifestyle. The majority of interventions in this field are cognitive behavioural, to instil positive beliefs, and encourage healthy behaviours and lifestyles.

Secondly, behavioural changes resulting from cognitive impairment are linked to structural anomalies in the brain caused by MetS (1,7). For instance, the impact of MetS on memory has been demonstrated in multiple studies, with this cognitive impairment potentially resulting in significant behavioural issues for patients (12-14).

It is recommended that both preventive and therapeutic interventions are added to clinical guidelines for MetS management. This will help prevent the behavioural disorders caused by cognitive impairments in patients. The identification of structural brain correlates of health-related behaviours provides a foundation for the development of more effective behavioural interventions. This is achieved by mapping the corresponding brain regions and implementing brain-targeted behavioural interventions (31-33).

In light of all this, it is on the one hand important to consider the various disorders that may be present when developing cognitive-behavioural interventions for MetS. On the other, large-scale studies should be addressed to gain a full understanding of the structural changes in the brain of people with MetS, the associated behaviours and their management.

Cognitomics: the Link of Cognitive Function and Disease

The majority of neurocognitive interventions for metabolic syndrome have historically sought to modify lifestyles and reduce risky behaviours. However, there has been a notable lack of focus on the neural mechanisms essential for maintaining these healthy behaviours, a topic explored within social neuroscience. It is becoming increasingly clear that key brain regions, such as the superior medial frontal cortex, play a vital role in controlling behaviours like appetite. There is a growing consensus that improving the function of these areas could be crucial for achieving lasting behaviour change. To this end, effective interventions should first pinpoint and target the neural bases of the desired change.

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