Background: Recent studies suggested that the visceral fat could exert a predictive role in the pathogenesis of dementia. The aims of the present study were to evaluate a) the possible correlation between the epicardial adipose tissue (EAT) thickness and the cognitive impairment; b) the possible predictive role of the EAT levels on cognitive functioning. Methods: 65 community-dwelling subjects were enrolled. The metabolic proﬁle was assessed through the evaluation of the biochemical parameters whereas the EAT thickness was measured through the transthoracic echocardiography. The Mini Mental State Examination (MMSE) was also administered. Results EAT thickness values showed several significant correlations with the variables examined in the study and a strong negative correlation with the MMSE scores (r= -.68; p=.001) was found. The multiple linear regression analysis showed that the EAT thickness levels and the hypertension had a predictive effect on the MMSE scores. Conclusions These preliminary findings support the association between EAT thickness levels and cognitive impairment

Andreozzi, Paola

Cacciafesta, Mauro

Magro, Valerio Massimo

Musumeci, Marco

Renzi, Alessia

Verrusio, Walter

Annali dell'Istituto Superiore di Sanità

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Key words
• epicardial fat thickness
• cardiometabolic risk
• cognitive impairment
• visceral fat
Association between epicardial fat 
thickness and cognitive function  
in elderly. A preliminary study
Walter Verrusio1, Alessia Renzi2, Valerio Massimo Magro3, Marco Musumeci1,  
Paola Andreozzi4 and Mauro Cacciafesta1
1Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche e Geriatriche, 
Sapienza Università di Roma, Rome, Italy 
2Dipartimento di Psicologia Dinamica e Clinica, Sapienza Università di Roma, Rome, Italy 
3Dipartimento di Medicina Interna e Geriatria, Università della Campania “Luigi Vanvitelli”, Naples, Italy 
4Dipartimento di Medicina Clinica, Sapienza Università di Roma, Rome, Italy
Ann Ist Super Sanità 2019 | Vol. 55, No. 1: 59-62
DOI: 10.4415/ANN_19_01_11
Abstract
Background. Recent studies suggested that the visceral fat could exert a predictive role 
in the pathogenesis of dementia. The aims of the present study were to evaluate: i) pos-
sible differences between groups with different epicardial adipose tissue (EAT) thickness 
on the included variables; ii) the possible predictive role of the EAT levels on cognitive 
functioning. 
Methods. 65 community-dwelling subjects were enrolled and divided into two groups: 
EAT < 7 mm (n = 36); EAT > 7 mm (n = 29). The metabolic proﬁle was assessed through 
the evaluation of the biochemical parameters whereas the EAT thickness was mea-
sured through the transthoracic echocardiography. The Mini Mental State Examination 
(MMSE) was also administered. 
Results. The two EAT groups reported several significant differences, included on the 
MMSE scores. The multiple linear regression analysis showed that the EAT thickness 
levels and the hypertension had a predictive effect on the MMSE scores. 
Conclusions. These preliminary findings support the association between EAT thickness 
levels and cognitive impairment. 
INTRODUCTION
A multifactorial pathogenesis is assumed for dementia. 
Indeed, while cardiovascular and metabolic factors are 
acknowledged as being relevant in the pathogenesis of 
“vascular dementia”, growing interest has been reported 
about the potential role of these factors in degenerative 
dementia as well. The importance of such factors is still 
controversial and research on this matter is being carried 
out. Over the past years, the role of adipose tissue as a 
possible risk factor has stirred great interest. By releas-
ing different mediators, adipose tissue exerts a negative 
action on different organs and systems, including the 
cardiovascular [1] and nervous systems [2]. Adipose tis-
sue can be classified according to its position in subcu-
taneous or visceral. In the latter type, epicardial adipose 
tissue (EAT) presents a unique location, being close or 
in contact with the heart and the coronary arteries. EAT 
is an energy source regulating the homeostasis of fatty 
acids for coronary circulation. Moreover, it produces a 
“cocktail” of cytokines (IL-6, TNF-α), adipokine (adi-
ponectine), microRNA and other cell mediators (leptin, 
angiotensinogen, resistin), playing a fundamental role in 
the paracrine regulation of vascular tone, in muscular 
smooth vascular cell proliferation and migration, and in 
susceptibility to atherosclerosis [2].
Over time, more and more convincing evidence has 
led researchers to believe that this tissue could be in-
volved, through a pathogenic pattern of “initial local 
inflammation”, in different cardiometabolic phenom-
ena such as insulin resistance and atherosclerosis. Thus, 
it can be concluded that EAT represents an authentic 
cardiovascular risk factor [3]. Nevertheless, the role of 
EAT in the development of cognitive impairments is 
still to be clarified. More specifically, can EAT thick-
ness be considered a reliable or predictive indicator for 
cognitive impairment? 
The primary aim of this study is to evaluate possible 
differences in both cognitive function and several vas-
Address for correspondence: Walter Verrusio, Scienze Cardiovascolari, Respiratorie, Nefrologiche, Anestesiologiche e Geriatriche, Sapienza Università 
di Roma, viale del Policlinico 155, 00161 Rome, Italy. E-mail: walter.verrusio@uniroma1.it.
Walter Verrusio, Alessia Renzi, Valerio Massimo Magro et al.
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cular risk factors (e.g. hypertension, diabetes, metabol-
ic parameters) in groups with different levels of EAT 
thickness.
Furthermore, a secondary aim of the study is to evalu-
ate the possible predictive role of both the EAT levels 
and the vascular risk factors on the cognitive functioning.
 
MATERIALS AND METHODS
65 community-dwelling Caucasian subjects with a 
mean age of 72.1 years (standard deviation = 8.9; 31 
males) followed by our Department for the evaluation 
of the functional status participated in this study. Exclu-
sion criteria were: infectious diseases, thoracic trauma, 
surgical procedures in the last 90 days, alcohol or drug 
addiction, psychiatric disorders, depression, hypo- or 
hyperthyroidism, anemia by any cause, heart failure, or 
condition of being chronically ill and treatment with che-
motherapeutic or hormonal agents. All procedures per-
formed in this study which involved human participants 
were in accordance with our institutional research com-
mittee (15th of November 2017) and with the 1964 Hel-
sinki Declaration and its later amendments or compa-
rable ethical standards. Informed consent was obtained 
from all individual participants included in the study.
The same day of the enrollment in the study each 
patient underwent a clinical interview, a physical ex-
amination, an anthropometric assessment and the ve-
nous blood sampling. Waist circumference (WC) was 
measured at the level of iliac crest in standing patients. 
After an overnight fast, standard laboratory techniques 
were used to determine the plasma total cholesterol 
(TC), high-density lipoprotein cholesterol (HDLc), tri-
glycerides (TG) and fasting blood glucose (FBG). 
Transthoracic two-dimensional (2D) guided M-mode 
echocardiography was performed in each subject us-
ing a Philips iE-33 machine (ultrasound device iE33 by 
Philips Ultrasound Inc., USA). Epicardial fat was rec-
ognized as the echo-free space between the outer wall 
of the myocardium and the visceral layer of pericardi-
um at end-systole in three cardiac cycles. We measured 
EAT thickness on the free wall of the right ventricle 
from both parasternal long- and short-axis views. The 
maximum values at any site were measured, and the 
average value was considered. Different cut-off points 
of epicardial fat thickness for cardiometabolic risk pre-
diction have been proposed [3]. Considering the het-
erogeneity of our sample in terms of cardiovascular risk 
factors, a threshold value of 7 mm thickness was fixed, 
in line with Natale et al. that set the normal upper limit 
to 7 mm [3, 4]. The clinical cut-off for EAT thickness 
values (= 7) was used in order to divide the sample in 
two groups: Increased EAT thickness level (n = 29, mean 
age = 73.9; SD = 8.3, 17 M; EAT mean values = 7.9; = 
1.1) and Normal EAT thickness level (n = 36, mean age = 
70.6; SD =  9.3, 14 M; EAT mean values = 5.6;  = .82).
The cognitive function was assessed through the Mini 
Mental State Examination (MMSE) which maximum 
score is 30. A score below 27 is indicative of an in-
creased risk of cognitive dysfunctions and dementia [5].
Hypertension was defined as a systolic arterial pres-
sure (SBP) > 140 mmHg and a diastolic arterial pres-
sure (DBP) > 90 mmHg or as reporting an history of 
use of antihypertensive medication, according to the 
WHO guidelines. Diabetes was defined as the pres-
Table 1
Differences between groups with normal and increased levels of epicardial adipose tissue (EAT) thickness
Parameters (n = 65) Epicardial adipose tissue thickness
< 7 mm (36) > 7 mm (29)
f p
M SD M SD
Age 70.61 9.3 73.93 8.3 2289 0.13 (ns)
FBG 94.89 13.1 107.10 12.1 14983 0.001**
WC 89.17 11.0 100.15 14.3 12203 0.001**
HDLc 57.28 9.74 49.14 17.2 5790 0.02*
TG 114.98 23.8 138.90 45.33 7479 0.008**
MMSE 28.31 1.06 24.67 1.35 16320 0.001**
n % n % χ2 p
Gender
Male
Female
14
22
38.9
61.1
17
12
58.6
41.4
2507 0.09 (ns)
Hypertension 
No 
Yes
11
25
30.6
69.4
0
29
0
100
10666 0.001**
Diabetes 
No
Yes
32
4
88.9
11.1
15
14
51.7
48.3
11079 0.001**
MetS 
No
Yes
34
2
94.4
5.6
2
27
6.9
93.1
49820 0.001**
*p < 0.05; **p <0.01. FBG: fasting blood glucose; WC: waist circumference; HDLc: high-density lipoprotein cholesterol; TG: triglycerides; MMSE: Mini Mental State 
Examination;  MetS: Metabolic syndrome.
Epicardial fat and cognition
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ence of the fasting plasma glucose levels of 126 mg/dl 
(7 mmol/ l) or the presence of non-fasting blood glucose 
values equal to or greater than 200 mg/dl (11.1 mmol/l) 
or a history of diabetes treatment [6]. Impaired fast-
ing glucose (IFG) was defined by FBG concentrations 
within the range 100-125 mg/dL [7]. Metabolic syn-
drome was diagnosed, according to National Choles-
terol Education Program (NCEP) ATP III 2001 criteria 
[8], by the presence of three or more of the following 
features: WC ≥ 88 cm in women and ≥ 102 cm in men; 
HDLc < 50 mg/dL in women and < 40 mg/dL in men; 
FBG ≥ 100 mg/dL and/or antidiabetic treatment; fast-
ing triglycerides ≥ 150 mg/dL; SBP ≥ 130 mmHg and/
or DBP ≥ 90 mmHg and/or antihypertensive treatment. 
All statistical analyses were performed using the Sta-
tistical Package for the Social Science (SPSS) version 
24 for Windows. Data are presented as means and  for 
continuous variables and as frequencies for discrete 
variables. One-way analysis of variance (ANOVA) was 
performed to investigate possible differences between 
groups in continuous variables while the Chi-square 
test (χ2) was used to explore differences between 
groups in discrete variables. A linear multiple regression 
model was performed in order to verify the predictive 
role of EAT, FBG, WC, HDLc, TG, MMSE, gender 
(0 = female; 1 = male), hypertension (0 = no; 1 = yes) 
and diabetes (0 = no; 1 = yes) on the MMSE scores. All 
the independent variables were entered simultaneously. 
Regression coefficients along with their 95% confidence 
interval (CI) were reported. A p value below .05 was 
considered statistically significant.
RESULTS
Data analysis showed that the two groups were ho-
mogenous for the variables age and gender, whereas 
significant differences emerged in all the other variables 
examined (Table 1). More specifically the group with 
EAT > 7 mm showed higher levels of FBG, WC and TG 
and lower levels of HDLc and MMSE compared to the 
group with EAT < 7 mm. Furthermore, the group with 
EAT > 7 mm reported a significantly higher frequency 
of patients suffering from hypertension, diabetes and 
metabolic syndrome compared to the group with EAT 
< 7 mm.
The multiple linear regression analysis revealed the 
absence of collinearity problems (tolerance index>.50; 
VIF< 2). The model explains the 55% of the MMSE 
scores (R2=.55; adjusted R2=.48). The independent vari-
ables who showed a predictive effect on the MMSE 
scores were: EAT (beta = -.49; 95% CI = -1,110 − -.344; 
p <.001), and hypertension (beta = -.21; 95% CI = 
-2.398 − -.59; p = .04) (Table 2). The variable MetS was 
not included in the regression model because the diag-
nosis of MetS depends on other variables which were 
included in the analysis.
DISCUSSION
In accordance with the findings of other authors [9], 
a connection between increased EAT thickness and 
MetS and its components was reported. EAT thick-
ness enables a more reliable evaluation of visceral fat 
than WC. Furthermore, in order to calculate visceral 
fat, EAT is measurable with good sensitivity and speci-
ficity by means of ultrasound techniques (lower costs), 
whereas other techniques are inevitably less manage-
able and very expensive, such as magnetic resonance 
(MR) or dual-energy X-ray absorptiometry, DXA [10]. 
Although vascular risk factors including hypertension, 
diabetes and dyslipidaemia have been implicated in the 
risk of cognitive dysfunction [2], only in Mazzoccoli et 
al. an association between epicardial fat thickness and 
cognitive impairment in the elderly was found [11]. In 
our study the negative correlation between the EAT 
thickness and the MMSE was confirmed. The way in 
which such an interesting correlation is obtained, at 
least from an ethio-pathogenic point of view, is still to 
be clarified and investigated. Visceral fat, including EAT, 
could have an injurious effect on cognitive abilities be-
cause of the intermediation of several cytokine and non- 
cytokine molecules it produces. This is well described in 
cardiovasculpathic patients [2] but we still lack clinical 
studies with patients suffering from Mild Cognitive Im-
pairment (MCI) or dementia. There are, nonetheless, 
known to be differences among patients with cognitive 
decline, about prognostic outcomes in relation to in-
flammatory status. In this light, the EAT would play a 
dual role as a pathogenetic factor as well as a potentially 
reversible risk factor. Moreover, several studies show a 
Table 2
Regression model reporting the predictive effect on Mini Mental State Examination scores of the variables included
Variables Beta 95% CI t p
EAT -0.494 -1.110 -0.344 -3.800 0.001**
FBG -0.135 -0.058 0.016 -1.130 0.263
WC -0.018 -0.039 0.034 -0.156 0.877
HDLc 0.051 -0.029 0.045 0.432 0.668
TG -0.176 -0.023 0.002 -1.658 0.103
Gender -0.078 -1.276 0.599 -0.723 0.473
Hypertension -0.213 -2.398 -0.059 -2.104 0.040*
Diabetes 0.029 -0.999 1.276 0.244 0.808
Age -0.187 -0.093 0.002 -1.901 0.063
*p < 0.05   **p < 0.01. EAT: epicardial adipose tissue; FBG: fasting blood glucose; WC: waist circumference; HDLc: high-density lipoprotein cholesterol; TG: 
triglycerides.
Walter Verrusio, Alessia Renzi, Valerio Massimo Magro et al.
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close correlation between EAT and cardiac function, 
regulated by the autonomous nervous system, with a re-
duction of the para-sympathetic activity and significant 
consequences in terms of arrhythmia and, indirectly, 
brain activity [12]. In this perspective, associating epi-
cardial fat and sympathetic nervous system by utilizing 
an accurate and easily reproduced method such as the 
assessment of heart rate variability (HRV), could rep-
resent a further item to explore cognitive decline and 
frailty [13]. Finally, there are genetic factors implied in 
the regulation of epicardial fat thickness and these fac-
tors are also correlated with insulin resistance, forming 
a sort of model that includes dementia- inducing dis-
eases such as Alzheimer’s, as well as metabolic patholo-
gies like diabetes [14]. Familiarity with these genes and 
understanding of their function could contribute, in 
turn, to better understanding the role played by EAT in 
both pathologies, as well as clarifying the mechanisms 
through which it performs its negative action [15].
The results of this study need to be interpreted in 
the light of some limitations. Firstly, we did not use 
the most accurate tools for the evaluation of visceral 
fat (e.g. whole-body magnetic resonance imaging). Sec-
ondly, the relatively limited sample size. Thirdly, our re-
sults suffer from a lack of knowledge about the inflam-
matory status of the patients.
CONCLUSIONS
The results of our study highlight that EAT thick-
ness, measured by transthoracic echocardiography, is 
inversely related to cognitive function. Based on our 
study, the transthoracic echocardiography proved to 
be simple and affordable. For this reason, it is realistic 
to suggest its application among elderly people whose 
physical changes can play an important role in deter-
mining biases in the anthropometric parameters rou-
tinely used. 
Author contributions
Verrusio W, Magro VM and Renzi A were the primary 
researchers and wrote the manuscript. Andreozzi P and 
Musumeci M provided research and editing assistance 
to the manuscript. Andreozzi P and Cacciafesta M con-
tributed to overall article design, data collection as well 
as revising and approving the manuscript.
Conflict of interest statement
None. This research did not receive any funding from 
agencies in the public, commercial, or not-for-profit 
sectors.
Received on 27 September 2018.
Accepted on 7 January 2019.
REFERENCES
1. Kouli GM, Panagiotakos DB, Kyrou I, et al. Visceral 
adiposity index and 10-year cardiovascular disease inci-
dence: the ATTICA study. Nutr Metab Cardiovasc Dis. 
2017;27(10):881-9
2. Bednarska-Makaruk M, Graban A, Wis´niewska A, et al. 
Association of adiponectin, leptin and resistin with in-
flammatory markers and obesity in dementia. Biogeron-
tology. 2017;18(4):561-80.
3. Iacobellis G, Howard JW. Echocardiographic Epicardial Fat: 
A review of research and clinical applications Journal of the 
American Society of Echocardiography. 2009;22(12):1311-
9. DOI: https://doi.org/10.1016/j.echo.2009.10.013
4. Natale F, Tedesco MA, Mocerino R, et al. Visceral adi-
posity and arterial stiffness: echocardiographic epicardial 
fat thickness reflects, better than waist circumference, 
carotid arterial stiffness in a large population of hyperten-
sives. Eur J Echocardiogr. 2009;10:549-55.
5.  Folstein MF, Folstein SE, McHugh PR. “Mini-men-
tal state”. A practical method for grading the cogni-
tive state of patient for the clinician. J Psychiatr Res. 
1975;12(3):189-98.
6. Irazola V, Rubinstein A, Bazzano L, et al. Prevalence, 
awareness, treatment and control of diabetes and im-
paired fasting glucose in the Southern Cone of Latin 
America. Plos One. 2017;6;12(9):e0183953.
7. American Diabetes Association. Standards of medical 
care in diabetes-2011. Diabetes Care. 2011;34(Suppl 
1):S11-61.
8. Executive Summary of The Third Report of The Na-
tional Cholesterol Education Program (NCEP) Expert 
Panel on Detection, Evaluation, And Treatment of High 
Blood Cholesterol in Adults (Adult Treatment Panel III). 
JAMA. 2001;16;285(19):2486-97.
9. Karadag B, Ozulu B, Ozturk FY, Oztekin E, Sener N, 
Altuntas Y. Comparison of epicardial adipose tissue 
(EAT) thickness and anthropometric measurements in 
metabolic syndrome (MS) cases above and under the age 
of 65. Arch Gerontol Geriatr. 2011;52(2):e79-84. DOI: 
10.1016/j.archger.2010.06.016.
10. Andreozzi P, Verrusio W, Viscogliosi G, et al. Relation-
ship between vitamin D and body fat distribution evalu-
ated by DXA in postmenopausal women. Nutrition. 
2016;32(6):687-92. 
11. Mazzoccoli G, Dagostino MP, Vinciguerra M, et al. An 
association study between epicardial fat thickness and 
cognitive impairment in the elderly. Am J Physiol Heart 
Circ Physiol. 2014;1;307(9):H1269-76.
12. Balciogˇlu AS, Cıçek D, Akinci S, et al. Arrhythmogenic 
evidence for epicardial adipose tissue: heart rate variabil-
ity and turbulence are influenced by epicardial fat thick-
ness. Pacing Clin Electrophysiol. 2015;38:99-106.
13. Vistisen ST, Jensen J, Fleischer J, et al. Association be-
tween the sensory-motor nervous system and the auto-
nomic nervous system in neurorehabilitation patients with 
severe acquired brain injury. Brain Inj. 2015;29(3):374-9.
14. Wang XF, Lin X, Li DY, et al. Linking Alzheimer’s dis-
ease and type 2 diabetes: Novel shared susceptibil-
ity genes detected by cFDR approach. J Neurol Sci. 
2017;15;380:262-72.
15. Mazzoccoli G, Dagostino MP, Paroni G, et al. Analysis of 
MTNR1B gene polymorphisms in relationship with IRS2 
gene variants, epicardial fat thickness, glucose homeosta-
sis and cognitive performance in the elderly. Chronobiol 
Int. 2017;14:1-11.


Association between epicardial fat thickness and cognitive function in elderly. A preliminary study

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Association between epicardial fat thickness and cognitive function in elderly. A preliminary study

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