When discussing weight and health, we usually think of the cardiovascular system, diabetes, or metabolic processes. However, a growing body of scientific evidence suggests that obesity (BMI ≥ 30 kg/m²) is also associated with brain health, memory, and cognitive function.
In a review published in the prestigious scientific journal Nature Reviews Neurology, researchers from the University of Michigan, together with international colleagues, analyzed clinical and preclinical studies investigating the link between obesity, brain health, and cognitive functions.
The review draws on data from various population, epidemiological, and clinical studies summarizing the global epidemiology of obesity and its clinical significance as a risk factor for the development of cognitive impairment and dementia.
To study the connection between obesity and brain health, scientists across various studies utilized methods for assessing brain structure and cognitive functions, as well as analyses of biological and metabolic markers. The following 4 points describe the biological, neuronal, metabolic, and molecular markers and mechanisms:
Functional changes in the hippocampus and prefrontal cortex: The hippocampus and prefrontal cortex are key regions of the brain responsible for memory formation and storage, learning, concentration, and executive functions. Metabolic and inflammatory stress associated with obesity can trigger hyperactivation of microglia—the brain’s immune cells—leading to neuronal synapse damage and reduced synaptic plasticity. In addition, localized vascular impairments and cellular metabolic dysfunction reduce energy uptake by neurons, which, over the long term, may contribute to functional and volumetric declines in these structures.
Chronic low-grade inflammation: Excess adipose tissue promotes the overproduction of pro-inflammatory cytokines and sustains chronic inflammation. These peripheral inflammatory signals affect the blood-brain barrier—a specialized protective structure that safeguards brain tissue from harmful substances and pathogens in the blood. Chronic inflammation can disrupt tight junctions between barrier cells and increase permeability, facilitating the development of inflammatory processes within the central nervous system.
Vascular and metabolic changes: Chronic inflammation and lipid disorders associated with obesity can cause deterioration of cerebrovascular function, negatively impacting optimal blood supply and normal operation of brain tissue. Furthermore, peripheral insulin resistance contributes to the impairment of insulin signaling pathways in the brain. Since insulin plays a role in regulating neuronal metabolism, synaptic plasticity, and cell survival in the brain, insulin resistance can disrupt the metabolic and signaling processes involved in memory formation and cognitive functions.
The hypothalamus and two-way feedback: Obesity can disrupt the functioning of the hypothalamus—the region of the brain involved in regulating hunger, satiety, and energy balance. Under normal conditions, leptin (the satiety hormone) produced in adipose tissue and insulin secreted by the pancreas reach the hypothalamus via the bloodstream to signal fullness to the brain. However, in obesity, elevated saturated fatty acids in the blood and inflammatory molecules released from excess adipose tissue activate brain immune cells (microglia and astrocytes), causing localized neuroinflammation in the hypothalamus. This process reduces hypothalamic sensitivity to these hormones, leading to leptin resistance and insulin resistance, thereby weakening the brain’s response to satiety signals. These changes make appetite control and maintaining a healthy weight more difficult, contributing to sustained obesity.
Results from high-tech neuroimaging studies conducted to examine structural brain changes indicate that obesity is associated with anatomical alterations in the brain.
Reduction in gray matter volume: According to some neuroimaging studies, a higher body mass index is associated with lower gray matter volume in brain regions such as the prefrontal cortex (involved in decision-making, self-control, and impulse management), the hippocampus (linked to memory and learning ability), and the striatum (involved in motivation and the reward system). Additionally, scientists note that in cases of weight loss, neuroimaging in certain studies showed partial recovery of brain gray matter volume, which may also translate to improved cognitive skills. However, further research is required to determine the magnitude and durability of these effects.
Microstructural changes in white matter: Studies suggest that a high body mass index may be linked to alterations in the structural features of white matter. White matter consists of nerve fibers (the brain’s “wiring”) and the myelin sheath, which provides electrical insulation and prevents nerve signal dissipation. Consequently, disruptions in the density and integrity of these structures can slow down or hinder information exchange between different brain regions.
Brain functional connectivity changes and cognitive assessment (cognitive skills)
Functional magnetic resonance imaging (fMRI) studies reveal that reward and motivation regions in individuals with obesity may activate more intensely in response to visual cues of high-calorie food, whereas activity in the prefrontal cortex—involved in impulse control—may be relatively lower. Put simply, the urge to eat increases while the “braking” mechanism weakens. These data lead researchers to hypothesize that such an imbalance between cognitive control and stimulus-response systems may complicate dietary self-regulation and food restriction.
Moreover, due to potential reductions in hippocampal volume, individuals with obesity may more frequently exhibit declines in episodic memory, making it harder to recall or retrieve specific events, facts, and details.
“Two-way” vicious cycle
Scientific literature suggests that this relationship may form a two-way vicious cycle: functional changes in brain networks responsible for self-control and behavioral regulation can foster impulsive eating, leading to weight gain. On the other hand, metabolic, inflammatory, and vascular disruptions linked to excess weight can cause additional structural changes in the brain and impair cognitive abilities, making it harder to break out of this cycle.
Long-term longitudinal observations suggest that individuals who experience obesity in midlife (ages 40-50) may face a higher risk of developing Alzheimer’s disease or vascular dementia in older age compared to individuals with normal weight.
The authors of the review emphasize that managing obesity through a healthy diet, physical activity, and, where necessary, medication or bariatric surgery, may represent an important strategy for reducing the risk of obesity-related cognitive impairment and dementia. However, these approaches do not guarantee dementia prevention, and further research is needed to determine their precise impact.
