CORRELATION OF VISCERAL FAT LEVEL AND POOR COGNITIVE FUNCTION AMONG ELDERLY POPULATION IN GIANYAR BALI

NEUROLOGY | ORIGINAL ARTICLE

CORRELATION OF VISCERAL FAT LEVEL AND POOR

COGNITIVE FUNCTION AMONG ELDERLY

POPULATION IN GIANYAR BALI

ABSTRACTVisceral adipose tissue is more metabolically active and has a stronger influence on adipocytokine produc-tion. One of the main characteristics of visceral adipose tissue is its lipolysis ability which is stronger than others adipose tissue so that the number of free fatty acid in portal circulation will be a higher and increasing risk of developing insulin resistance. Visceral adipose tissue’s hormones are more proatherogenic. This research aims to find out whether visceral adipose tissue is correlated with poor cognitive performance and hopefully could fill the gap between one to another research and to prevent the poor cognitive performance by controlling the level of visceral adipose tissue regularly. We used a cross-sectional analytical study. The sample was recruited using total sampling method by collecting all elderly population in 5 elderly integrated healthcare centre located in Gianyar in July 2017. We obtained 107 samples. Visceral adipose tissue level was measured using Omron HBF 510 Body Composition Monitor with Scale, and cognitive performance was measured using a structured questionnaire Mini Mini State Examination (MMSE). Correlation test result using the gamma test showed that visceral adipose tissue was correlated moderately with poor cognitive performance ( γ0.413 and p 0.003).

KEYWORDSvisceral adipose tissue, leptin, cognitive performance, elderly, systemic inflammation

Introduction

Obesity is one of the significant health problems in almost every country in the world. Globalization development has influenced our lifestyle, and the number of obesity prevalence is increasing every year. World Health Organization (WHO) reports there are at least 1,4 billion people in this world who categorized as overweight with Body Mass Index (BMI) around 25 – 29.9 kg/m2 while another 500 million has BMI≥30.0 kg/m2 which means they suffered obesity.[1] High level of adipose tissue has a strong Copyright © 2020 by the Bulgarian Association of Young Surgeons

DOI:10.5455/IJMRCR.visceral-fat-level First Received: December 08, 2019 Accepted: January 09, 2020

Manuscript Associate Editor: Ivan Inkov (BG)

1_{Internal Medicine Department, Udayana Medical Faculty / Udayana University}

Hospital, email: [email protected]

correlation with a high risk of various metabolic diseases such as cardiovascular diseases, type 2 diabetes melitus (T2DM) and even several types of cancer. Obesity at the individual level is an interaction between genetic and environmental factors where environment factors were suspected play the more critical role than the others since fact showed that obesity’s prevalence has been increasing in the last 30 years as much as the globalization era grows. Lately, some researches showed that obesity has an adverse effect on brain structure. Rajik et al. (2010) found there was a poor cognitive function in a patient with high visceral fat level.[2,3]

The human brain is a vital organ that regulates the home-ostasis of energy. The brain controls homehome-ostasis level sub-consciously through hypothalamus while non – homeostasis circuit located in a structure outside hypothalamus.4 Those in-tegrated processes control our body weight so that it remains stable throughout our life. Rapid development in medical imag-ing also has significant effects in this case since they helped us detecting the change of the brain’s structure better than before.

Obesity was suspected related to poor grey matter density in prefrontal, somatosensory, insular, temporal and subcortical area compared to non – obesity subjects. [3,4]

Most of the studies were using BMI as a parameter to define obesity objectively while the remains measured waist circum-ference to define how much fat accumulation in the abdomen area. Visceral fat has emerged as the key pathogenic depot and having a stronger association with adipocytokines production and insulin resistance so that it strongly correlates to various metabolic diseases and poor cognitive function.[5] BMI is the most accessible parameter to measure obesity however it seems less representative since people with normal BMI have possibil-ity to have high visceral fat level too.

Published data on the association of visceral fat level and poor cognitive function among the elderly still lack pieces of evidence due to limited study about this topic. Raschpiler et al. (2013) found that poor grey matter density correlates to high visceral fat level, while Debette et al. (2010) showed the opposite. Many studies showed contradictive results compared to each other and there’s the only limited study about this topic; thus, further study is needed. This study aims to know whether high visceral fat levels correlate to poor cognitive function or not and hopefully it could fill the gap in the prior study. Last but not least, we hope this study could help to decrease poor cognitive impairment among elderly patients through better prevention.

Picture 1:Visceral Fat Levels of Samples (in %).

Picture 2:MMSE Score Results (in %).

Methods

This study is an analytical study, using a cross-sectional design and aims to study the correlation between the visceral fat level and cognitive function among the elderly population (≥60 years old) in Gianyar regency. Samples were enrolled using total sampling method, which means we took all elderly population from 5 elderly integrated healthcare centre in Gianyar on July 2017. We found 107 samples in total.

Visceral fat levels were measured using Omron HBF 510 Body Composition Monitor with Scale. This device is similar to weigh scales; however, we need to input sample personal information first such as age, gender and height before using this device. When it is done, the sample can step on the main unit barefoot. Right posture for measurement is standing barefoot with knees and back straight and look straight ahead, raise arms horizontally and extend elbow straight to form 90 degrees angles to the body, hold the display unit with both of your hands. Omron has higher accuracy compared to other similar devices and research showed that Omron accuracy has nearly the same with hydrodensitometry, Dual Energy X-ray Absorptiometry (DXA) and Magnetic Resonance Imaging (MRI). The results then classified in three categories which is 0 means normal, + means high, and ++ means very high. If the scored was 1 – 9 so it considered as 0 categories (normal), when the score was 10-14 so it considered as + (high) while the score was 15 – 30 then it considered as ++ (very high).

Global cognitive function was measured objectively using a structured questionnaire called Mini Mini State Examination (MMSE). MMSE consists of several questions to measured orien-tation, registration, attention, calculation, memory and language ability. The result is ranging from 0 as minimum score and 30 as the maximum score where a higher score reflects better cognitive function. Those scores then classified again into three categories, 0 – 19 is definitely dementia disorder, 20 – 24 is suspected de-mentia disorder and 25-30 is normal cognitive function.

Results

Sample Characteristics

Data from 107 samples of elderly (≥60 years old) are reported. Their mean age (SD) was 69.23 years old, where the smallest age was 60 years old, and the oldest one was 98 years old. Most of the samples were women (56.1%) and the remaining 47 sam-ples (43.9%) were men. We divided education background into several categories where uneducated was 45 samples (42%), ele-mentary school was 35 samples (32.7%), junior high school was 15 samples (14%), high school was eight samples (7.5%), the bachelor was four samples (3.8%). Their average BMI was 23.95 kg/m2 ranging from 13.7 kg/m2 until 37.7 kg/m2. Sample char-acteristics based on their resting metabolism level was 1234.95 in average where the smallest and the biggest is 14 and 1760 respectively, while mean body fat level percentage was 33.04% where the lowest and highest is 14% and 45.8%.

Correlation of Visceral Fat Levels and Poor Cognitive Function

As mentioned above, visceral fat levels in the sample were mea-sured using Omron HBF 510 Composition Monitor and divided into three categories as normal, high and very high. Statistical analysis towards visceral fat level showed 53 samples (49.4%) has normal visceral fat level, 31 samples (28.7%) has high vis-ceral fat level and remaining 23 samples (21.8%) has a very high

Table 1Demographic Characteristics of Sample.

Variable Numbers (n)

Percentage

(%) Variable Mean (SD) Range Gender : Man Woman Education background : Uneducated Elementary school Junior high school High school Bachelor 47 60 45 35 15 8 4 43.9 56.1 42 32.7 14 7.5 3.8 Age BMI Bodyweight Resting Metabolism Body Fat Percentage 69.23±7.90 23.95±4.86 57.25±12.05 1234.95±253.69 33,04±8.26 60-98 13.7-37.7 32 – 81.6 14 – 1760 14 – 45.8

Table 2Crosstabulation of Visceral Fat Level and Cognitive Function.

MMSE Value Total Normal Suspected dementia Dementia Visceral Fat Levels Normal Count % 27 51.3% 15 27.9% 11 20.8% 53 100% High Count % 7 24% 14 44% 10 32% 31 100% Very high Count

% 5 21.1% 8 36.8% 10 42.1% 23 100% Total Count % 39 36.8% 37 34.5% 31 28.7% 107 100%

Table 3:Gamma Correlation Test Result.

visceral fat level (picture 1). MMSE score as cognitive function parameter also categorized in 3 different levels where 39 samples (36.8%) has the normal cognitive function, 37 samples (34.5%) considered having suspect dementia disorder, and 31 samples (28.7%) has dementia (picture 2).

The cross-tabulation analysis showed 53 samples with nor-mal visceral fat level, most of them have a nornor-mal cognitive function (51.3%) whereas only 15 samples (27.9%) suspected having dementia and only 20.8% has a poor cognitive function. The second group was high visceral fat level group consists of 31 samples in total. Sample with high visceral fat level tends to have poor cognitive function according to the MMSE test result. Total numbers of the sample with the high visceral level were 31 samples, 14 samples (44%) were suspected having dementia disorders, ten samples (32%) definitely have dementia and only remaining 7 (24%) have a normal cognitive function. Next group was very high visceral fat level group consisted of 23 samples in total where most of them (42.1%) have dementia, eight samples (36.8%) suspected having dementia and an only small number

from them (21.1%) have a normal cognitive function.

Gamma correlation test was performed to test the association between visceral fat level and cognitive function among the elderly population in Gianyar Bali. The gamma correlation test showed in Table 3, p-value 0.003, which means visceral fat level and poor cognitive function, was significant clinically. Gamma correlation score was 0.413 means that they have an average correlation so that the higher visceral fat levels, the poorer cognitive function.

Discussion

According to research and analysis result that has been done above, it showed that visceral fat level has an average corre-lation with poor cognitive function. Visceral fat is stored ab-dominal cavity and several vital organs such as hepar, pancreas, and intestines. Other fat storage was below our skin so that it often called subcutaneous fat.[6] Compared to subcutaneous adipose tissue, the visceral adipose tissue has been considered as a pathogenic adipose tissue compartment. One of the mech-anisms is the sustained exposure of the liver to an increased flux of free fatty acid via the portal circulation from the visceral adipose tissue may be antecedent to the disturbances in glu-cose and lipid metabolism and it will increase the chance of insulin resistance. Hormones produced by visceral fat tissue has a proatherogenic effect. Visceral fat tissue is more metabolically active and has stronger association towards adipocytokine pro-duction like adiponectin, tumour necrosis factor (TNF) α and

plasminogen activator inhibitor type I.[7] Visceral fat effect on various metabolic and cardiovascular diseases have been stud-ied extensively, however, study of visceral fat effect on poor cognitive function in elderly still limited until now.

The study conducted by DH Yoon et al. (2012) strongly sup-port our hypothesis in this study. They found that visceral fat and poor cognitive function were associated with each other. DH Yoon et al. used a CT Scan to measured visceral fat level, and they conclude visceral fat was an independent factor and strongly correlated to poor cognitive function. They even ex-cluded several comorbid factors of cardiovascular disease yet vis-ceral fat remains correlated to poor cognitive function. Visvis-ceral fat can be caused by the development of lesion in brain white matter. In transgenic animal models, leptin receptor-deficient rodents were shown to have impaired memory performances, long term potentiation of neurons in the hippocampus. Leptin resistance in obesity is one of the important keys in developing poor cognitive function.[8]

The first followed 1.423 individuals in the Framingham Heart Study for 4-6 years and found that higher BMI was associated with worse cognitive function scores in men alone.[9] We pre-fer measured visceral fat using Omron so that the results we obtained are more accurate compared to those who are using BMI to measure visceral fat level. BMI often didn’t represent the actual percentage of visceral level since its possible having high visceral fat level while BMI still in the normal range. Some pilot studies that using BMI as a parameter have shown no correlation between BMI and poor cognitive function, and this phenomenon can be explained, especially in the elderly popula-tion (> 60 years old). Muscle mass in elderly is decreasing as the age goes older, and it will be replaced with fat mass; therefore, their body weight remains stable. That phenomenon is one of the reasons why we didn’t use BMI as a visceral fat level param-eter and prefer Omron which can give us more accurate data on the visceral fat level.

The decreasing of cognitive function in the elderly was strongly suspected due to brain structure changing. Higher visceral fat was associated with regional cortical thinning such as decreasing hippocampus volume, increasing ventricle size, poor memory ability and also thinning several areas of brain cortical. All of those changing contributed to poor cognitive function in human.[10] A study from Walther et al. (2010) has shown reduced grey matter density with increasing visceral fat in left inferior frontal, right posterior region, right precen-tral region, right lingual using voxel-based morphometric. The underlying mechanism of those facts still hasn’t been under-standing clearly until now. Some of the studies suggested that brain structure changing was strongly associated with obesity itself. T2DM is strongly correlated to obesity and suspected to be one of the underlying mechanisms that cause brain structure changes. However, that hypothesis remains speculative because in the present dataset after excluded diabetic subjects but was still able to show an independent effect of visceral fat on brain structure.[11]

Systemic inflammation could be another critical mediator. Inflammation is essential mediator since obesity has been corre-lated to the massive production of inflammation markers. Cy-tokines such as interleukin six and tumour necrosis factor-alpha are produced in adipose tissue and induce hepatic production of CRP. Adipose tissue itself contained various inflammatory cells such as monocyte and macrophage that accumulates in obese people. Inflammation was shown to predict a higher risk of

dementia. In Framingham offspring study, found that inflamma-tion markers were inversely associated with total brain volume. Persons on anti-inflammatory drugs show significantly smaller age-related volume changes in regions of both grey and white matter compared to controls. Another mechanism was probably through hypercortisolemia state, hyperlipidemia, and decreas-ing physical activity. Hypercholesterolemia was contributed to hippocampus atrophy.

A similar study found that high-level visceral tissue con-tributes to decreasing grey matter density from the cerebellum, where this finding also consistent with another study that used different parameters such as BMI or waist circumference. The newest finding of cerebellum function shown that cerebellum plays a role in the motoric process not only in the cognitive pro-cess. Moreover, cerebellum showed higher glucose metabolic activity and there was significant blood flow decrease to the cere-bellum in obesity sample. Interestingly, the cerecere-bellum expresses the FTO gene, which is associated with both overall obesity and very recently visceral adipose tissue.[12]

The adipocyte-derived hormone leptin may provide further explanations for the correlation of visceral fat and poor cognitive function in the elderly. Leptin is predominantly produced in white subcutaneous tissue, messages the switch between the starved and fed states and serves as an essential factor for the development of leptin sensitive, hypothalamic feeding circuits. Its signal is conveyed via the long isoform of leptin receptors (Ob-Rb). This receptor’s mRNA was shown to be present in the cerebellum. Moreover, Ob-Rb mRNA levels in both rodents and humans exceed all other tissues investigated, including the hy-pothalamus.[13] Leptin also plays a role in the relation between adipose tissue and brain atrophy. In transgenic animal models, leptin receptor-deficient rodents were shown to have impaired memory performances and long term potentiation of neurons in the hippocampus. Leptin has also been shown to reduce the extracellular amyloid-beta load and the level of tau phospho-rylation in neuronal cells.[10] Framingham cohort study has identified a positive correlation between leptin level in plasma and grey matter volume in the right hippocampus. The higher circulating leptin levels were significantly associated with a re-duced risk of incident dementia and brain atrophy. Leptin was expressed more in subcutaneous fat tissue compared to visceral fat tissue. Obesity people tend to have lower leptin level and have an increased risk of poor cognitive function. Guftasin et al. (2008) have supported the idea about leptin roles in the poor cognitive function where leptin and other fat-derived hormones can cross the blood-brain barrier so they may disturb cognitive brain function through the various mechanism. [13]

Conclusion

Visceral fat tissue has been considered as a pathogenic adi-pose tissue compartment. It is more metabolically active a has stronger association towards adipocytokine production like adiponectin, tumour necrosis factor (TNF) α and plasminogen ac-tivator inhibitor type I.[7] Visceral fat is strongly correlated with increased risk of metabolic diseases and poor cognitive func-tion. The result of this study has shown a significant correlation between the visceral fat level and poor cognitive performance. The underlying mechanism remains speculated; however, some suspected mechanisms are systemic inflammation, chronic expo-sure to free fatty acid and leptin role. All of those mechanisms will directly influence brain volume, a brain structure in some brain regions so that they may be caused poor cognitive function

later.

There were only limited published studies about this topic thus we need more studies with a larger sample and represent the actual population, better design and method with longer follow up time and also more accurate sample enrollment so that sample will be more homogenous and exclude some con-founding variables. In this study, we use MMSE as cognitive function parameter while the visceral fat level was measured using Omron. We hope that further study will be done by bet-ter and more accurate modality such as MRI to measure brain structure changing and CT–scan to measure visceral fat level and therefore the results will be more actual and representative. We hope this study could help better prevention if dementia prevalence in elderly by doing more physical activity and regu-lar control of body weight so that excessive visceral fat level can be avoided.

Disclosure Statement

There were no financial support or relationships between the authors and any organization or professional bodies that could pose any conflict of interests.

Competing Interests

Written informed consent obtained from the patient for publica-tion of this case report and any accompanying images.

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