1,721,085 research outputs found

    Cognitive assessment with neurocognitive screening tools

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    Neurocognitive Disorders (NCDs) are widespread diseases, especially in elderly. The future possibility of having more effective treatments has to deal with the lack of early disorder detection, which would enable patients to benefit the most from them. Individual medical history, blood and cerebrospinal fluid tests, and neuroimaging, among other tools, support the diagnostic process; neurocognitive screening tests also have an irreplaceable role to play in NCD assessment. Ease of execution and low cost make these instruments to be so appreciate in clinical practice. Mini Mental State Examination (MMSE), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Montreal Cognitive Assessment (MoCA), and Clock Drawing Test (CDT), used as first-level screening tools, will be at the centre of this mini review. In the present work we will highlight the contribution made by these tests in NCD assessment, emphasizing some interesting aspects recently emerged from the scientific literature

    Mononuclear cells in dementia

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    According to the World Health Organization statistics, dementias are the largest contributors to disease burden in advanced market economies, and the leading cause of disability and dependence among older people worldwide. So far, several techniques have been developed to identify dementias with reasonable accuracy while the patient is still alive, however, no single of them has proven to be ideal, especially if you need to have a satisfactory early diagnosis. Studies of early onset dementia are largely limited by the inaccessibility to direct examination of the living human brain: it appears therefore that for a correct biochemical and molecular characterization of dementias, potential surrogate tissues must be identified. In this context, peripheral blood mononuclear cells (PBMCs) appear particularly attractive because they can be obtained in a minimally invasive manner and can be easily analyzed. This review focuses on the most representative methodologies and strategies in detecting and quantifying fluctuation in dementia that are currently being developed. In addition it provides a comprehensive evaluation of the diagnostic sensitivity of PBMCs in patients with dementia. Finally, it discusses the data supporting the use of the determination of neutral lipids (NLs) in PBMCs by Oil Red O (ORO) staining, which is a minimally invasive, cheap, easy and fast procedure, as the promising method for early detection of dementia and to search for new effective treatments

    Physical Performance and Falling Risk Are Associated with Five-Year Mortality in Older Adults: An Observational Cohort Study

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    Background: Falls in older people have a significant impact on public health. The scientific literature has provided evidence about the necessity for older adults to be physically active, since it reduces the incidence of falls, several diseases, and deaths, and can even slow down some effects of aging. The primary aim of our study is to identify if physical performances and risk of falling are related to 1-, 2-, 3-, 4-, and 5-year mortality. Its secondary aim is to establish if people with both severely impaired physical performance and a high risk of falling also present impairment in other geriatric domains. Methods: In this prospective study, we enrolled subjects aged 65 years or more, subjected them to comprehensive assessment (including assessment of risk of falling, physical capacities, comorbidities, autonomies in daily living, cognitive abilities, mood, and nutritional status), and followed them for 5 years. Results: We included 384 subjects, 280 of whom were women (72.7%), with a median age of 81 years. Our results showed that physical performances and risk of falling are highly correlated to each other (rho = 0.828). After divided the sample into three groups (people without augmented risk of falling and able to perform adequate physical activity; people with moderate risk of falling and/or disability; people with severe risk of falling and/or disability), we found that the more severe the disability and risk of falling were, the more compromised the other geriatric domains were. Moreover, the survival probability progressively increased following the same trend, amounting to only 41% in severely compromised people, 51.1% in moderately compromised people, and 62.8% in people without physical compromise nor an augmented falling risk (p = 0.0124). Conclusions: Poor physical performance combined with a high risk of falling, correlated with each other, are associated with higher mortality and impairment in multiple domains in older adults

    Neutral Lipid Determination in Peripheral Blood Mononuclear Cells: A Useful Tool for Diagnostic and Therapeutic Interventions in Dementia

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    The objective of this review was to focus on recent studies indicating how deregulation of lipid metabolism may be of particular importance for central nervous system (CNS) injuries and neurodegenerative disorders. Furthermore, since an accumulation of neutral lipids (NLs), mainly cholesterol esters (CEs) in the form of cytoplasmic lipid droplets was previously found by our group in peripheral blood mononuclear cells (PBMCs) of Alzheimer (AD) patients and their first degree relatives (AD-FDR), we reviewed current data providing evidence that altered lipid metabolism in brain can also affect cholesterol metabolism in the systemic circulation. Using data from literature we proposed a mechanistic model that helps us to explain why subjects with neurological disorders often accumulate NLs in their PBMCs. If validated by future research, it should provide a rationale for NL-PBMCs determination by Oil Red O (ORO) staining method as a useful tool for diagnostic and therapeutic interventions in AD and possibly in other forms of dementia occurring in childhood as well as in elderly

    Nutritional status and oxidative stress in an elderly Sardinian population

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    Weight loss and overweight/obesity – frequent consequences of malnutrition – may impair functional status and worsen concomitant morbidities in the elderly, often through changes in oxidative balance. In order to verify the relationships between these factors, a group of elderly people living on the island of Sardinia (Italy) underwent health and nutritional status assessment and oxidative balance evaluation. The elderly subjects had significantly higher d-ROMs test and body mass index (BMI) values than controls (d-ROMs 325.4 ± 66.3 vs. 295.4 ± 58.9 CARR U, p = 0.006; BMI 28.0 ± 4.6 vs. 21.7 ± 1.4 kg/m2, p < 0.0001). The risk of malnutrition in the elderly subjects was evaluated with the Mini Nutritional Assessment (MNA), which showed that 32 of the 111 elderly subjects (28.8%) were at risk of malnutrition, of whom 11 (34%) were overweight and 10 (31.2%) obese. Oxidative stress was negatively and significantly correlated with nutritional status. Oxidative stress may precede malnutrition, even in the absence of weight loss. Routine evaluation of nutritional status and oxidative balance in the elderly may help identify an early risk of malnutrition so that treatment can be personalized

    Cholesterol esterification as a mediator of proliferation of vascular smooth muscle cells and peripheral blood mononuclear cells during atherogenesis

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    Background/Aims: We determined growth rates, cholesterol esterification and mRNA levels for caveolin-1 (Cav-1), neutral cholesterol esters hydrolase (n-CEH) and ATP-binding cassette transporter (ABCA-1), in quiescent and growth-stimulated peripheral blood mononuclear cells (PBMCs) and intimal vascular smooth muscle cells (VSMCs) from blood and primary atherosclerotic plaques, respectively. These cells were cultured in the presence or absence of the mTOR inhibitor 40-O-(2-hydroxyethyl) rapamycin (RAD). Methods: The rate of cell proliferation was determined by 3H-thymidine incorporation into DNA and that of lipid metabolism by utilizing 14C-acetate and 14C-oleate as precursors. Lipid deposit in the vascular cells was evaluated by Oil Red O staining and lipid mass by thin layer chromatography-linked enzymatic assay. Results: Growth stimulation of PBMCs and VSMCs caused a rapid increase in intracellular cholesterol esterification and an accumulation of cholesterol esters (CEs) accompanied by a reduction of free cholesterol (FC) and Cav-1, ABCA-1 and n-CEH mRNAs. RAD reduced intracellular lipid accumulation in growth-stimulated cells and also increased expression of Cav-1, n-CEH and ABCA-1 genes. Conclusion: Collectively, these data provide evidence that the determination of CEs in PBMCs may be an easy prescreening test to identify subjects at risk for vascular proliferative disease and that FC, CE, Cav-1, n-CEH and ABCA-1 may be suitable targets for antiproliferative therapies

    Cholesterol, Alzheimer’s Disease, Prion Disorders: a ménage à trois?

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    Aberrant folded proteins are hallmarks of amyloidogenic diseases. Examples are Alzheimer's disease (AD) and prion-related disorders (PrD). These disorders, although clinically different, have the same underlying pathogenetic mechanism: an altered protein conformer with high β-sheet structure content: the amyloid beta peptide (Aβ) in the case of AD, and the aberrant prion protein, PrPsc in PrD. Although the molecular processes that cause these proteins to adopt non-native structures in vivo and become cytotoxic are still largely unknown, there is good reason to expect prion research to profit from advances in the understanding of AD, and vice versa. Growing evidence indicates that the various pathways of lipid/lipoprotein metabolism play a key role in AD and PrD pathophysiology. These findings clearly highlight the possible involvement of cholesterol in misfolded protein generation. In this review, we focus on recent studies which provide evidence that membrane domains, called lipid rafts, directly promote protein misfolding, and that this process takes place only if changes occur in the fine regulation of intracellular cholesterol. In addition, we discuss the implications of these results to introduce the concept that pharmacological interventions restoring cholesterol homeostasis could have potential preventive/therapeutic value against the progression of misfolding disorders. The aim of the review is to provide researchers with a general understanding of cholesterol’s involvement in protein folding/misfolding processes which may be relevant for knowledge advancement regarding amyloidogenic proteins, and possible ways to prevent their pathological activity
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