The Neurological Consequences of Obesity

By Marina Artemiou

Obesity is a medical condition in which excess body fat accumulates in the body to the extent that it may cause adverse effects on a person’s health. Commonly, the BMI or Body Mass Index is used to classify overweight and obesity in adults, although it does not take into consideration the amounts of fat or muscle in the body and can sometimes misclassify people into incorrect categories. For adults, the World Health Organization defines overweight at a BMI greater than or equal to 25, and obesity at a BMI greater or equal to 30 (WHO, 2020). 

Throughout the past 45 years, the accessibility and availability of food has increased dramatically in most parts of the world, all while advances in technology and methods of transportation have enabled the world’s population to become increasingly sedentary. This has led to the tripling of worldwide obesity since 1975. By 2016, approximately 39% of adults aged 18 and over were classified as overweight, whilst 13% were classified as obese. Subsequently, obesity has been categorised as a global preventable pandemic. More recently, obesity and diet-induced metabolic dysfunction have been identified as risk factors for a variety of neurological disorders of both the central and peripheral nervous system (WHO, 2020).

Increased caloric intake and decreased energy expenditure result in a net energy overload, leading to adipose tissue expansion, adipocyte hypertrophy and hyperplasia, and alteration of adipokine secretion resulting in tissue inflammation. Visceral adipose tissue expansion activates adipose tissue macrophages and subsequently the rate of lipolysis increases. As a result, circulating free fatty acid (FFA) concentration rises and contributes to the development of metabolic dyshomeostatis. Obesity-induced metabolic dyshomeostatis affects the autonomic, central and peripheral nervous systems due to the lipotoxic effect of dyslipidemia; unhealthy levels of one or more kinds of lipids (HDL, LDL and triglycerides) in the blood, and increased FFA concentration in systemic circulation. The dysfunction of homeostasis has been shown to lead to mild cognitive impairment and Alzheimer’s disease in the central nervous system as well as neuropathy in the autonomic and peripheral nervous systems (Raji et al, 2010).

A range of evidence exists showing that obesity can cause a clear and distinct reduction in overall brain size. A 2.4% decrease in brain parenchymal volume has been observed in obese individuals when compared to individuals with a normal BMI. Moreover, obesity-related atrophy has been observed in the hippocampus, cingulate gyrus and frontal lobes and has been linked to a continuous decline in executive function, i.e. working memory, planning, emotional control, etc, over a 10-year period. The atrophy observed is believed to be a result of a reduction in neuronal fibre bundle length due to increased age as well as higher BMI. Additionally, cognitive testing studies have demonstrated that the extensive levels of cerebral atrophy observed in morbidly obese individuals, and older individuals, are correlated with impaired cognitive function, i.e. loss in memory, attention span, etc (Raji et al., 2010).

As mentioned above, increasing amounts of evidence supports that elements of the central nervous system are adversely affected by obesity. Meta-analysis has shown a strong correlation between mid-life obesity and neurological disorders such as dementia and Alzheimer’s disease. There was an indication that obesity doubled the risk of developing Alzheimer’s disease when compared to individuals with normal weight, while post-mortem studies conducted on the brain of afflicted individuals displayed higher levels of hippocampal markers, β-amyloid and β-amyloid precursor proteins, than non-afflicted individuals (Abcam, 2020). 

The excessive presence of such markers was an extremely pivotal discovery as Alzheimer’s disease is characterised by the presence of neurotoxic β-amyloid plagues in the brain, formed when monomeric β-amyloid peptides spontaneously assemble into soluble oligomers which in turn cluster together to form insoluble fibrils. Despite the exact mechanism for the contribution of neurotoxic plagues in the development of Alzheimer’s still being under debate, it is generally agreed upon that such markers provide a characteristic for this specific condition. Consequently, it is believed that bodily dyshomeostatis can lead to the upregulation of processes which stimulate the cleavage of healthy amyloid precursor proteins into pathogenic β-amyloid peptides, increasing plague formation and promoting Alzheimer’s disease development (Abcam, 2020).

Finally, conditions associated with obesity such as diabetes have been shown to act as the main metabolic drivers of peripheral neuropathy. Studies conducted in the United States, Shanghai and the Netherlands of individuals with prediabetes, diabetes and obesity have demonstrated higher incidences of neuropathy in individuals belonging to these groups of the population as opposed to healthy participants (Callaghan et al., 2020). Although the exact mode of action by which excess amounts of glucose damages nerves is unknown, a number of methods have been suggested. Researchers believe that uncontrolled high sugar levels can weaken the walls of capillaries supplying neurones with oxygen and nutrients, leading to neuronal damage and interfering with their ability to transmit electrical impulses (Mayo Clinic, 2020). 

With the rates of obesity continuing to rise globally, this issue has grown to epidemic proportions, with over 4 million people dying each year as a result of being overweight or obese. Obesity related disorders and their side-effects are burdening national health services in both first and third world countries, however the absence of a “quick fix” and easy treatments for this disorder means that the spread will not be stopped in the near future.


World Health Organization (WHO). (2020) Obesity and Overweight. Available from: 

Raji, C., et al. (2010) Human Brain Mapping. Brain Structure and Obesity. 31(3): 353–364. Available from: doi: 10.1002/hbm.20870

Abcam. (2020) Beta-amyloid and tau in Alzheimer’s disease. Available from: 

Callaghan, B., et al. (2018) Annals of Clinical and Translational Neurology. Diabetes and obesity are the main metabolic drivers of peripheral neuropathy. 5(4): 397–405. Available from: doi: 10.1002/acn3.531Mayo Clinic. (2020) Diabetic Neuropathy. Available from:

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