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      Adverse Associations between Visceral Adiposity, Brain Structure, and Cognitive Performance in Healthy Elderly


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          The link between central adiposity and cognition has been established by indirect measures such as body mass index (BMI) or waist–hip ratio. Magnetic resonance imaging (MRI) quantification of central abdominal fat has been linked to elevated risk of cardiovascular and cerebro-vascular disease. However it is not known how quantification of visceral fat correlates with cognitive performance and measures of brain structure. We filled this gap by characterizing the relationships between MRI measures of abdominal adiposity, brain morphometry, and cognition, in healthy elderly. Methods: A total of 184 healthy community dwelling elderly subjects without cognitive impairment participated in this study. Anthropometric and biochemical markers of cardiovascular risk, neuropsychological measurements as well as MRI of the brain and abdomen fat were obtained. Abdominal images were segmented into subcutaneous adipose tissue and visceral adipose tissue (VAT) adipose tissue compartments. Brain MRI measures were analyzed quantitatively to determine total brain volume, hippocampal volume, ventricular volume, and cortical thickness. Results: VAT showed negative association with verbal memory ( r = 0.21, p = 0.005) and attention ( r = 0.18, p = 0.01). Higher VAT was associated with lower hippocampal volume ( F = 5.39, p = 0.02) and larger ventricular volume ( F = 6.07, p = 0.02). The participants in the upper quartile of VAT had the lowest hippocampal volume even after adjusting for age, gender, hypertension, and BMI ( b = −0.28, p = 0.005). There was a significant age by VAT interaction for cortical thickness in the left prefrontal region. Conclusion: In healthy older adults, elevated VAT is associated with negative effects on cognition, and brain morphometry.

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          Aerobic fitness is associated with hippocampal volume in elderly humans.

          Deterioration of the hippocampus occurs in elderly individuals with and without dementia, yet individual variation exists in the degree and rate of hippocampal decay. Determining the factors that influence individual variation in the magnitude and rate of hippocampal decay may help promote lifestyle changes that prevent such deterioration from taking place. Aerobic fitness and exercise are effective at preventing cortical decay and cognitive impairment in older adults and epidemiological studies suggest that physical activity can reduce the risk for developing dementia. However, the relationship between aerobic fitness and hippocampal volume in elderly humans is unknown. In this study, we investigated whether individuals with higher levels of aerobic fitness displayed greater volume of the hippocampus and better spatial memory performance than individuals with lower fitness levels. Furthermore, in exploratory analyses, we assessed whether hippocampal volume mediated the relationship between fitness and spatial memory. Using a region-of-interest analysis on magnetic resonance images in 165 nondemented older adults, we found a triple association such that higher fitness levels were associated with larger left and right hippocampi after controlling for age, sex, and years of education, and larger hippocampi and higher fitness levels were correlated with better spatial memory performance. Furthermore, we demonstrated that hippocampal volume partially mediated the relationship between higher fitness levels and enhanced spatial memory. Our results clearly indicate that higher levels of aerobic fitness are associated with increased hippocampal volume in older humans, which translates to better memory function. Copyright 2008 Wiley-Liss, Inc.
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            Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI.

            We have used restriction isotyping (restriction enzyme isoform genotyping) for rapid typing of common apolipoprotein E isoforms (E2, E3, E4). ApoE restriction isotyping used oligonucleotides to amplify apolipoprotein E gene sequences containing amino acid positions 112 and 158. The amplification products were digested with HhaI and subjected to electrophoresis on polyacrylamide gels. Each of the isoforms was distinguished by a unique combination of HhaI fragment sizes that enabled unambiguous typing of all homozygotic and heterozygotic combinations. HhaI cleaves at GCGC encoding 112arg (E4) and 158arg (E3, E4), but does not cut at GTGC encoding 112cys (E2, E3) and 158cys (E2).
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              Frequent amyloid deposition without significant cognitive impairment among the elderly.

              To characterize the prevalence of amyloid deposition in a clinically unimpaired elderly population, as assessed by Pittsburgh Compound B (PiB) positron emission tomography (PET) imaging, and its relationship to cognitive function, measured with a battery of neuropsychological tests. Subjects underwent cognitive testing and PiB PET imaging (15 mCi for 90 minutes with an ECAT HR+ scanner). Logan graphical analysis was applied to estimate regional PiB retention distribution volume, normalized to a cerebellar reference region volume, to yield distribution volume ratios (DVRs). University medical center. From a community-based sample of volunteers, 43 participants aged 65 to 88 years who did not meet diagnostic criteria for Alzheimer disease or mild cognitive impairment were included. Regional PiB retention and cognitive test performance. Of 43 clinically unimpaired elderly persons imaged, 9 (21%) showed evidence of early amyloid deposition in at least 1 brain area using an objectively determined DVR cutoff. Demographic characteristics did not differ significantly between amyloid-positive and amyloid-negative participants, and neurocognitive performance was not significantly worse among amyloid-positive compared with amyloid-negative participants. Amyloid deposition can be identified among cognitively normal elderly persons during life, and the prevalence of asymptomatic amyloid deposition may be similar to that of symptomatic amyloid deposition. In this group of participants without clinically significant impairment, amyloid deposition was not associated with worse cognitive function, suggesting that an elderly person with a significant amyloid burden can remain cognitively normal. However, this finding is based on relatively small numbers and needs to be replicated in larger cohorts. Longitudinal follow-up of these subjects will be required to support the potential of PiB imaging to identify preclinical Alzheimer disease, or, alternatively, to show that amyloid deposition is not sufficient to cause Alzheimer disease within some specified period.

                Author and article information

                Front Aging Neurosci
                Front. Ag. Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Research Foundation
                15 July 2011
                13 September 2011
                : 3
                [1] 1simpleCognitive Neuroscience Laboratory, Neuroscience and Behavioural Disorders Program, Duke–National University of Singapore Graduate Medical School Singapore
                [2] 2simpleSchool of Computer Engineering, Nanyang Technological University Singapore
                [3] 3simpleYong Loo Lin School of Medicine, National University of Singapore Singapore
                Author notes

                Edited by: Vadim Fraifeld, Ben Gurion University of the Negev, Israel

                Reviewed by: William J. Jagust, University of California Berkeley, USA; Arie Budovsky, Judea R&D Center, Israel

                *Correspondence: Michael Chee, Cognitive Neuroscience Laboratory, Duke–National University of Singapore Graduate Medical School, 8 College Road, Singapore 169857. e-mail: michael.chee@ 123456duke-nus. edu.sg
                Copyright © 2011 Isaac, Sim, Zheng, Zagorodnov, Tai and Chee.

                This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

                Page count
                Figures: 2, Tables: 4, Equations: 1, References: 47, Pages: 8, Words: 6695
                Original Research

                visceral adiposity,cognitive aging,neuropsychological assessment,mri,hippocampus
                visceral adiposity, cognitive aging, neuropsychological assessment, mri, hippocampus


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