Markers of Visceral Adiposity for Dementia Risk Assessment. The Epicardial Adipose Tissue ( EAT ) Thickness

To the Editor: Dementia is among the most frequent causes of disability in older people. Although great efforts have been made in identifying clinical predictors of pathological cognitive decline over time, to date there is a lack of evidence-based preventive strategies and, even more, there is no evidence of treatments that effectively allow clinicians to modify dementia course.1, 2 Growing evidence indicates that traditional risk factors for cardiovascular (CV) diseases, and brain subcortical small vessels diseases, also represent potent additional risk factors for Alzheimer's dementia, the most frequent diagnosis worldwide, whose etiology has been traditionally attributed to a pure neurodegenerative process.2 Paralleling with the increase in life expectancy, Westernized societies are facing a pandemic of obesity- and sedentary-related diseases.3, 4 It has been estimated that around 40% of people ages 65 years and more carry the metabolic syndrome (MetS), a constellation of CV and metabolic risk factors including hypertension, altered glucose homeostasis, atherogenic dyslipidemia and abdominal obesity.3, 4 Peripheral insulin resistance and chronic micro-inflammation are thought to be the fundamental determinants of MetS, as both conditions importantly influence occurrence of the other diagnostic traits of MetS.4 Excessive abdominal visceral fat accumulation is typically associated with chronic elevation of pro-inflammatory cytokines and development of insulin resistance. Visceral adipose tissue colonization by activated macrophages is the key factor promoting chronic subclinical inflammation. Chronic secretion of pro-inflammatory cytokines, especially IL-1 and –6 and TNF-α, is closely associated with subsequent development of insulin resistance.4 MetS is risky for the aging brain, as it has been associated with greater occurrence and severity of cerebrovascular damage and accelerated cognitive decline.1, 2, 5 Growing evidence indicates that the risk of dementia associated with the MetS may be greater than that conferred by the sum of its altered components and cerebrovascular damage extent, and it may be largely mediated by chronic insulin resistance and inflammation.1, 5 It is well established that excessive abdominal fat accumulation, namely android obesity, is a robust predictor of CV events.4, 6 In clinical practice, systemic and central obesity are usually quantified using anthropometric measurements, e.g., body mass index, waist circumference, waist-to-hip ratio. However, clinical utility of such markers may be limited in older subjects, due to to aging-associated changes in body composition. Lean mass wasting, especially sarcopenia, may result in markedly reduced sensitivity of standard anthropometric measures in assessing adiposity in older adults. Studies investigating the relationships of MetS and obesity to cognitive function in late life have reported conflicting results, with authors suggesting that the relationship of MetS to dementia risk may be no more apparent in later life.7 We hypothesize that the aforementioned age-associated changes in body composition may partly explain such heterogeneity in results. Several studies have indicated that epicardial fat thickness may be a better predictor of incident CV events when compared to other proxies of visceral adiposity.8 Epicardial adipose tissue (EAT) is a part of visceral fat accumulated around the heart between visceral pericardium and myocardium, mostly lodged around coronary arteries.6, 9 Growing evidence indicates that EAT is closely associated with insulin resistance and chronic micro-inflammation.6, 9 Furthermore the greater the EAT thickness the greater the risk of coronary artery disease and stroke.8 To the best of our knowledge, there is only one published study reporting on the association between EAT extent and cognitive function.10 Authors have cross-sectionally found, in a sample of 71 older subjects, that EAT thickness, measured through trans-thoracic echocardiography, was significantly associated with poorer global cognitive performances, evaluated by MMSE. Furthermore the authors have shown that EAT mediated the relationships between MetS, insulin resistance and body mass index with MMSE performances. Building on the above-mentioned considerations, we believe that searching for accurate measures of visceral fat accumulation may add important information in assessing CV risk profile as well as in identifying older subjects with greater risk of accelerated cognitive decline over time. The echocardiographic assessment of EAT is an objective, noninvasive and inexpensive test that could be successfully implemented in clinical practice to reliably estimate visceral adiposity in older people.9 Given that the prevalence of dementia is expecting to double over the next decades, identification of potentially modifiable clinical markers predicting dementia over time may have great relevance for healthcare systems and societies as a whole. Future longitudinal studies are required to establish whether EAT thickness assessment may help in identifying individuals with greater risk of cognitive decline and dementia over time. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Giovanni Viscogliosi and Evaristo Ettorre: concept and preparation of manuscript; Iulia Maria Chiriac and Paola Andreozzi: literature review and data interpretation. Sponsor's Role: None.