Worldwide obesity has nearly tripled since 1975, with over 1.9 billion adults overweight, among which 650 million were obese, according to WHO [1] data in 2016. For people aged 60 and older, obesity prevalence is as high as 41.5% according to data from US CDC [2]. In Asia, very limited data on elderly obesity is available. A 2015 Malaysian survey [3] found that the prevalence of obesity in elderly group was 30.2%, lower than that of the US, but still a significant proportion. Previous recognized complications of obesity are well known: hypertension, dyslipidemia, diabetes, stroke, obstructive sleep apnoea, osteoarthritis and so on.
Back in 2021, a systematic review on 21 cohort studies globally [4] established the relationship between central obesity and incidence of cognitive impairment or dementia. Central obesity is defined by waist circumference or waist-to-hip ratio. The cohort study involved 21 studies with 5, 060, 687 participants and demonstrated that central obesity was associated with a greater risk of cognitive impairment and dementia, compared with healthy bodyweight. The study also commented that this link is only observable in individuals older than 65 years of age, and does not apply to people 65 years and younger.
Recently, a new study investigating the muscular adiposity and elderly cognitive decline has been published on Journal of the American Geriatrics Society [5] by Rosano et al. This study specifically looked at increase in skeletal muscle fat instead of central fat, and how this will be linked to the onset of dementia.
In the recruitment phase, it enrolled 3075 people in the US aged 70-79 and independently assessed their body composition, functional status and mortality between 1997-1998. They were followed up subsequently till 2011. The group obtained repeated measures of cognition (measured using 3MS score) and body compositions in Years 1, 3, 5, 8 and 10, including intermuscular adipose tissue (IMAT), visceral and subcutaneous fat, total fat mass and muscle area. Eventually 1634 participants met the criteria for inclusion.
In Figure 1, Means (standard errors) of 3MS in study Year 1 to 10, plotted separately for those with (red) and those without (Black) increase in thigh IMAT from study Year 1 to 6 (red: IMAT change >0; Black: IMAT change ≤0). Arrows indicate the two timepoints of IMAT measurements.
Figure 1
Thus, the study concluded that increasing skeletal muscle adiposity predicted declining cognitive function, independent of traditional risk factors for dementia and other body composition depots. But what’s the mechanism behind it? The author recognized previously proposed mechanisms including adiposity-related detrimental effects on glucose metabolism, and cardiometabolic conditions, such as diabetes and hypertension, which are known dementia risk factors. Meanwhile, ectopic adipose tissue is metabolically active thus releasing proinflammatory cytokines that have neurodegenerative effects and contribute to onset of dementia.
Irisin, is another neuroprotective cytokine, whose level might have been reduced due to fat infiltration to skeletal muscle. A study published in 2019 [6] has indicated that peripheral overexpression of irisin restores synaptic plasticity and memory in Alzheimer’s disease mouse models, and its reduction in circulating level attenuate the neuroprotective actions of physical exercise on synaptic plasticity.
Despite well-established risk factors for dementia however, we still have very limited treatment options for dementia patients, and their quality of life is much lower than that of the general public. Future research could focus on life-changing medications that can terminate the progress of dementia on top of lifestyle modifications.
Reference:
1.WHO. Obesity and Overweight [Internet]. World Health Organization. 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
2.CDC. Obesity is a Common, Serious, and Costly Disease [Internet]. Centers for Disease Control and Prevention. 2022. Available from: https://www.cdc.gov/obesity/data/adult.html#:~:text=The%20obesity%20prevalence%20was%2039.8
3.Ariaratnam S, Rodzlan Hasani WS, Krishnapillai AD, Abd Hamid HA, Jane Ling MY, Ho BK, et al. Prevalence of obesity and its associated risk factors among the elderly in Malaysia: Findings from The National Health and Morbidity Survey (NHMS) 2015. Lombardo M, editor. PLOS ONE. 2020 Sep 11;15(9):e0238566.
4.Tang X, Zhao W, Lu M, Zhang X, Zhang P, Xin Z, et al. Relationship between Central Obesity and the incidence of Cognitive Impairment and Dementia from Cohort Studies Involving 5,060,687 Participants. Neuroscience & Biobehavioral Reviews [Internet]. 2021 Nov 1 [cited 2023 May 20];130:301–13. Available from: https://www.sciencedirect.com/science/article/abs/pii/S014976342100378X
5.Rosano C, Newman A, Santanasto A, Zhu X, Goodpaster B, Miljkovic I. Increase in skeletal muscular adiposity and cognitive decline in a biracial cohort of older men and women. Journal of the American Geriatrics Society. 2023 Jun 7;
6.Lourenco MV, Frozza RL, de Freitas GB, Zhang H, Kincheski GC, Ribeiro FC, et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models. Nature Medicine [Internet]. 2019 Jan [cited 2019 May 22];25(1):165–75. Available from: https://www.nature.com/articles/s41591-018-0275-4
