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      Direct Measurements of Abdominal Visceral Fat and Cognitive Impairment in Late Life: Findings From an Autopsy Study

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          Abstract

          Background: The relationship between cognitive impairment and abdominal visceral is controversial. Moreover, all studies so far used imaging studies to evaluate visceral fat and this association has not been described yet using autopsy material, which allows the direct quantification of abdominal fat. We aimed to investigate the association between direct measurements of abdominal visceral fat and cognitive impairment in an autopsy study.

          Methods: In this cross-sectional study, we collected information on sociodemographics, cardiovascular risk factors, and cognitive status from subjects aged 50 or older at time of death in a general autopsy service in Brazil. Abdominal visceral fat was obtained in natura by the dissection of perirenal, mesenteric, omental, and mesocolon fat. The associations of total abdominal visceral fat with cognitive impairment [clinical dementia rating (CDR) score ≥0.5] and CDR-sum of boxes (CDR-SB) were evaluated using logistic regression and negative binomial regression models, respectively. All analyses were adjusted for height, age, sex, education, hypertension, diabetes mellitus, stroke, smoking, alcohol use, and physical inactivity. In addition, we compared the discrimination of visceral fat, body mass index (BMI), and waist circumference (WC) measurements in predicting cognitive impairment.

          Results: We evaluated 234 participants (mean age = 71.2 ± 12.9 years old, 59% male). Abdominal visceral fat was inversely associated with cognitive impairment (OR = 0.46, CI = 0.30; 0.70, p < 0.0001) and with CDR-SB scores ( β = −0.85, 95% CI = −1.28; −0.43, p < 0.0001). When we compared the area under the ROC curve (AUC), visceral fat (AUC = 0.754), BMI (AUC = 0.729), and WC (AUC = 0.720) showed similar discrimination in predicting cognitive impairment ( p = 0.38).

          Conclusion: In an autopsy study, larger amount of directly measured abdominal visceral fat was associated with lower odds of cognitive impairment in older adults.

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          Most cited references39

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          Overview of epidemiology and contribution of obesity to cardiovascular disease.

          The prevalence of obesity has increased worldwide and is a source of concern since the negative consequences of obesity start as early as in childhood. The most commonly used anthropometric tool to assess relative weight and classify obesity is the body mass index (BMI); BMI alone shows a U- or a J-shaped association with clinical outcomes and mortality. Such an inverse relationship fuels a controversy in the literature, named the 'obesity paradox', which associates better survival and fewer cardiovascular (CV) events in patients with elevated BMI afflicted with chronic diseases compared to non-obese patients. However, BMI cannot make the distinction between an elevated body weight due to high levels of lean vs. fat body mass. Generally, an excess of body fat (BF) is more frequently associated with metabolic abnormalities than a high level of lean body mass. Another explanation for the paradox is the absence of control for major individual differences in regional BF distribution. Adipose tissue is now considered as a key organ regarding the fate of excess dietary lipids, which may determine whether or not body homeostasis will be maintained (metabolically healthy obesity) or a state of inflammation/insulin resistance will be produced, with deleterious CV consequences. Obesity, particularly visceral obesity, also induces a variety of structural adaptations/alterations in CV structure/function. Adipose tissue can now be considered as an endocrine organ orchestrating crucial interactions with vital organs and tissues such as the brain, the liver, the skeletal muscle, the heart and blood vessels themselves. Thus, the evidence reviewed in this paper suggests that adipose tissue quality/function is as important, if not more so, than its amount in determining the overall health and CV risks of overweight/obesity. © 2013.
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            Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study.

            To evaluate any association between obesity in middle age, measured by body mass index and skinfold thickness, and risk of dementia later in life. Analysis of prospective data from a multiethnic population based cohort. Kaiser Permanente Northern California Medical Group, a healthcare delivery organisation. 10,276 men and women who underwent detailed health evaluations from 1964 to 1973 when they were aged 40-45 and who were still members of the health plan in 1994. Diagnosis of dementia from January 1994 to April 2003. Time to diagnosis was analysed with Cox proportional hazard models adjusted for age, sex, race, education, smoking, alcohol use, marital status, diabetes, hypertension, hyperlipidaemia, stroke, and ischaemic heart disease. Dementia was diagnosed in 713 (6.9%) participants. Obese people (body mass index > or = 30) had a 74% increased risk of dementia (hazard ratio 1.74, 95% confidence interval 1.34 to 2.26), while overweight people (body mass index 25.0-29.9) had a 35% greater risk of dementia (1.35, 1.14 to 1.60) compared with those of normal weight (body mass index 18.6-24.9). Compared with those in the lowest fifth, men and women in the highest fifth of the distribution of subscapular or tricep skinfold thickness had a 72% and 59% greater risk of dementia, respectively (1.72, 1.36 to 2.18, and 1.59, 1.24 to 2.04). Obesity in middle age increases the risk of future dementia independently of comorbid conditions.
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              Central obesity and increased risk of dementia more than three decades later.

              Numerous reports show that a centralized distribution of adiposity is a more dangerous risk factor for cardiovascular disease and diabetes than total body obesity. No studies have evaluated whether the same pattern exists with dementia. The objective was to evaluate the association between midlife central obesity and risk of dementia three decades later. A longitudinal analysis was conducted of 6,583 members of Kaiser Permanente of Northern California who had their sagittal abdominal diameter (SAD) measured in 1964 to 1973. Diagnoses of dementia were from medical records an average of 36 years later, January 1, 1994, to June 16, 2006. Cox proportional hazard models adjusted for age, sex, race, education, marital status, diabetes, hypertension, hyperlipidemia, stroke, heart disease, and medical utilization were conducted. A total of 1,049 participants (15.9%) were diagnosed with dementia. Compared with those in the lowest quintile of SAD, those in the highest had nearly a threefold increased risk of dementia (hazard ratio, 2.72; 95% CI, 2.33-3.33), and this was only mildly attenuated after adding body mass index (BMI) to the model (hazard ratio, 1.92; 95% CI, 1.58-2.35). Those with high SAD (>25 cm) and normal BMI had an increased risk (hazard ratio, 1.89; 95% CI, 0.98-3.81) vs those with low SAD ( 30 kg/m(2)) and with high SAD had the highest risk of dementia (HR, 3.60; 95% CI, 2.85-4.55). Central obesity in midlife increases risk of dementia independent of diabetes and cardiovascular comorbidities. Fifty percent of adults have central obesity; therefore, mechanisms linking central obesity to dementia need to be unveiled.
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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                07 May 2019
                2019
                : 11
                : 109
                Affiliations
                [1] 1Department of Pathology, University of São Paulo Medical School , São Paulo, Brazil
                [2] 2Department of Biomedicine, Federal University of ABC , São Paulo, Brazil
                [3] 3Experiment Pathophysiology Program, University of São Paulo Medical School , São Paulo, Brazil
                [4] 4Division of Geriatrics, University of São Paulo Medical School , São Paulo, Brazil
                [5] 5Department of Medical Surgical Nursing, University of São Paulo School of Nursing , São Paulo, Brazil
                [6] 6Department of Neurology, Memory and Aging Center, University of California, San Francisco , San Francisco, CA, United States
                [7] 7Department of Neurology, University of São Paulo Medical School , São Paulo, Brazil
                Author notes

                Edited by: Ines Moreno-Gonzalez, University of Texas Health Science Center at Houston, United States

                Reviewed by: Ville-Petteri Makinen, South Australian Health and Medical Research Institute (SAHMRI), Australia; Magda Tsolaki, Aristotle University of Thessaloniki, Greece

                *Correspondence: Claudia K. Suemoto cksuemoto@ 123456usp.br
                Article
                10.3389/fnagi.2019.00109
                6524696
                31133846
                de41aae1-7fd0-4140-9c9b-dff253516703
                Copyright © 2019 Nishizawa, Cuelho, de Farias-Itao, Campos, Leite, Ferretti-Rebustini, Grinberg, Nitrini, Jacob-Filho, Pasqualucci and Suemoto.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 October 2018
                : 25 April 2019
                Page count
                Figures: 3, Tables: 4, Equations: 0, References: 49, Pages: 8, Words: 6288
                Funding
                Funded by: Fundação de Amparo á Pesquisa do Estado de São Paulo 10.13039/501100001807
                Award ID: 2013/12290-3
                Funded by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 10.13039/501100002322
                Categories
                Neuroscience
                Original Research

                Neurosciences
                aging,autopsy,obesity,dementia,abdominal fat
                Neurosciences
                aging, autopsy, obesity, dementia, abdominal fat

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