Obesity in middle age is associated with an increased risk of dementia. With more than a third of all adults now overweight, the prevention of obesity and its consequences is of utmost importance.
Increased BMI in middle age significantly increases the risk of dementia, possibly due to increased inflammation and increased levels of cytokines and hormones produced in adipocytes.1 Obesity may also contribute to the development of vascular dementia by not only worsening cerebral perfusion, but also increasing fat cells that damage white matter, ultimately leading to cognitive and intellectual decline.
New results from the English Longitudinal Study of Ageing (ELSA) now provide further evidence for a positive and independent association between obesity and dementia risk.
In a representative sample of 6,582 older adults (> 50 years, mean age: 63 years) in England, three out of four participants (74%) who developed dementia within the 15-year follow-up period were overweight or obese at baseline.2
This association appeared to be mediated mainly by obesity, rather than its sequelae (such as hypertension, cardiovascular disease and diabetes):
Compared to normal weight participants, overweight individuals had a 34% increased risk of developing dementia - and this was independent of sex, age, apolipoprotein E-ε4 (APOE-ε4), education level, physical activity, smoking and marital status. After additional correction for hypertension and diabetes, the risk was still 31% greater.
Biologically, excess body fat is associated with alterations in energy metabolism, accumulation of cerebral lesions and measurable brain atrophy (an early marker of neurodegeneration).2 In recent years, there has been growing evidence that the link between poor nutrition and cognitive impairment may be explained in relevant part by the gut microbiome or gut-brain axis.
In metabolic diseases, the inflammatory system is activated, which also spreads to the brain and disrupts synaptic plasticity there. This leads to neurodegeneration and eventually to brain volume loss. A common trigger for this inflammatory activation may lie in the composition of the gut microbiome and gut mycobiome. Diet influences the composition of gut microbiota, for example, eating too many simple carbohydrates and sugars can cause an imbalanced gut microbial population.1,3
A 2018 review lists other risk factors for dementia and obesity in middle age, such as low-dose exposure to organochlorine pesticides - OCPs (wood preservatives, insecticides, e.g. dichlorvos, DDT, lindane), exposure to which is increasing in the general population. OCPs are lipophilic, i.e. they are stored by the fatty tissue, released and slowly metabolised over the years. They have half-lives of several years and their serum concentration is equal to the concentration in the brain. Therefore, it can be said that any condition that promotes the release of organochlorine pesticides from adipose tissue can increase the risk of dementia. Some of these conditions may be dysfunctional adipocytes causing uncontrolled lipolysis. Since obesity is the most common cause of dysfunctional adipocytes, obesity in middle age can significantly increase the risk of dementia.1
Given the rise in obesity rates, this data from the ELSA study again highlights that obesity is a growing and serious problem for individuals and society. It is estimated that 39% of adults worldwide were overweight in 2016.4 What is outlined here may help explain why global dementia rates almost tripled between 1975 and 2016.5,6
However, few countries have currently formulated national dementia plans and most interventions to date have focused on lifestyle factors other than obesity.
"These findings have important implications for the design of appropriate interventions to prevent and manage factors contributing to obesity and its consequences [...]," the study authors conclude.2
References:
1. Anjum, I., Fayyaz, M., Wajid, A., Sohail, W. & Ali, A. Does Obesity Increase the Risk of Dementia: A Literature Review. Cureus 10, (2018).
2. Ma, Y., Ajnakina, O., Steptoe, A. & Cadar, D. Higher risk of dementia in English older individuals who are overweight or obese. International Journal of Epidemiology 49, 1353-1365 (2020).
3. Solas, M., Milagro, F. I., Ramírez, M. J. & Martínez, J. A. Inflammation and gut-brain axis link obesity to cognitive dysfunction: plausible pharmacological interventions. Current Opinion in Pharmacology 37, 87-92 (2017).
4. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128-9 million children, adolescents, and adults. Lancet 390, 2627-2642 (2017).
5. Ahmadi-Abhari, S. et al. Temporal trend in dementia incidence since 2002 and projections for prevalence in England and Wales to 2040: modelling study. BMJ 358, j2856 (2017).
6. Being overweight is linked with an increased risk of dementia in new research. NIHR Evidence https://evidence.nihr.ac.uk/alert/overweight-linked-increased-risk-dementia/ doi:10.3310/alert_45547.