436 research outputs found

    Is left-handedness associated with a more pronounced age-related cognitive decline?

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    The effect of handedness on cognitive functioning has been the subject of much controversy. The influential "pathological left-handedness theory" posited by Coren and Halpern (1991) claims that left-handedness is probabilistically related to deviations from the neurological and cognitive norm. Many studies have failed to find negative effects of left-handedness on cognitive functioning, but most of these studies related handedness to cognition at one moment in time. Such studies do not exclude the possibility that sinistrality may be related to a more pronounced age-related longitudinal decline in cognitive functions. This hypothesis was tested in the present study. In a longitudinal study involving a large population sample of cognitively intact people aged at least 50 years at baseline, we evaluated the effect of handedness on age-related decline in four major cognitive domains: speed of information processing, verbal learning, long-term verbal memory, and executive functioning. The results failed to provide support for the hypothesis that sinistrality is associated with a more pronounced age-related cognitive decline. Recommendations for future studies are provided

    Rey's verbal learning test: normative data for 1855 healthy participants aged 24-81 years and the influence of age, sex, education, and mode of presentation

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    The Verbal Learning Test (VLT; Rey, 1958) evaluates the declarative memory. Despite its extensive use, it has been difficult to establish normative data because test administration has not been uniform. The purpose of the present study was to gather normative data for the VLT for a large number (N = 1855) of healthy participants aged 24-81 years, using a procedure in which the words to be learned were presented either verbally or visually. The results showed that VLT performance decreased in an a.-e-dependent manner from an early age. The learning capacity of younger versus older adults differed quantitatively rather than qualitatively. Females and higher educated participants outperformed males and lower educated participants over the entire age range tested. Presentation mode affected VLT performance differently: auditory presentation resulted in a better recall on Trial 1 (a short-term or working memory measure), whereas visual presentation yielded a better performance on Trial 3, Trial 4, and Delta (a learning measure)

    Klinische bruikbaarheid van categoriegebonden woordproductie voor het onderscheiden van dementie en normale cognitieve veroudering

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    Met behulp van multiple regressieanalyse op gegevens van de Maastricht Aging Study (MAAS; N=1.825; leeftijdsbereik 24-81 jaar) zijn normen berekend voor een veelgebruikte semantische fluencytest (dieren en beroepen opnoemen). Het aantal genoemde dieren, beroepen en de somscore van dieren en beroepen samen bleek sterk afhankelijk van demografische variabelen, zoals leeftijd en opleiding. Het regressiemodel is toegepast op de gegevens van 1.063 psychogeriatrische patiënten, onder wie 890 met alzheimerdementie of vasculaire dementie. Bij gelijke specificiteit was de sensitiviteit voor het onderscheid tussen dementie en normale cognitieve veroudering het hoogst voor het aantal genoemde dieren. Vijftig patiënten persevereerden over taken (zij noemden tijdens afname van de beroepenfluencytaak spontaan weer een of meer ‘dieren’). Dit verschijnsel kwam met 11,3% vaker voor bij parkinsondementie en de frontale variant van frontotemporale dementie dan bij alzheimerdementie (4,6%) en vasculaire dementie (5,3%). Persevereren over taken correleerde negatief met prestaties op een woordgeheugentaak, de EMCT (Expanded Mental Control Test), de BDS (Behavioral Dyscontrol Scale) en de meandertekening als een test voor verminderde responsinhibitie. In een multivariate logistische regressieanalyse correleerde alleen de meandertekening significant met persevereren over taken

    Neurophysiological effects of human-derived pathological tau conformers in the APPKM670/671NL.PS1/L166P amyloid mouse model of Alzheimer's disease

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    Alzheimer's Disease (AD) is a neurodegenerative disease characterized by two main pathological hallmarks: amyloid plaques and intracellular tau neurofibrillary tangles. However, a majority of studies focus on the individual pathologies and seldom on the interaction between the two pathologies. Herein, we present the longitudinal neuropathological and neurophysiological effects of a combined amyloid-tau model by hippocampal seeding of human-derived tau pathology in the APP.PS1/L166P amyloid animal model. We statistically assessed both neurophysiological and pathological changes using linear mixed modelling to determine if factors such as the age at which animals were seeded, genotype, seeding or buffer, brain region where pathology was quantified, and time-post injection differentially affect these outcomes. We report that AT8-positive tau pathology progressively develops and is facilitated by the amount of amyloid pathology present at the time of injection. The amount of AT8-positive tau pathology was influenced by the interaction of age at which the animal was injected, genotype, and time after injection. Baseline pathology-related power spectra and Higuchi Fractal Dimension (HFD) score alterations were noted in APP.PS1/L166P before any manipulations were performed, indicating a baseline difference associated with genotype. We also report immediate localized hippocampal dysfunction in the electroencephalography (EEG) power spectra associated with tau seeding which returned to comparable levels at 1 month-post-injection. Longitudinal effects of seeding indicated that tau-seeded wild-type mice showed an increase in gamma power earlier than buffer control comparisons which was influenced by the age at which the animal was injected. A reduction of hippocampal broadband power spectra was noted in tau-seeded wild-type mice, but absent in APP.PS1 animals. HFD scores appeared to detect subtle effects associated with tau seeding in APP.PS1 animals, which was differentially influenced by genotype. Notably, while tau histopathological changes were present, a lack of overt longitudinal electrophysiological alterations was noted, particularly in APP.PS1 animals that feature both pathologies after seeding, reiterating and underscoring the difficulty and complexity associated with elucidating physiologically relevant and translatable biomarkers of Alzheimer's Disease at the early stages of the disease

    Caspofungin Weight-Based Dosing Supported by a Population Pharmacokinetic Model in Critically Ill Patients

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    The objective of this study was to develop a population pharmacokinetic model and to determine a dosing regimen for caspofungin in critically ill patients. Nine blood samples were drawn per dosing occasion. Fifteen patients with (suspected) invasive candidiasis had one dosing occasion and five had two dosing occasions, measured on day 3 (±1) of treatment. Pmetrics was used for population pharmacokinetic modeling and probability of target attainment (PTA). A target 24-h area under the concentration-time curve (AUC) value of 98 mg·h/liter was used as an efficacy parameter. Secondarily, the AUC/MIC targets of 450, 865, and 1,185 were used to calculate PTAs for Candida glabrata, C. albicans, and C. parapsilosis, respectively. The final 2-compartment model included weight as a covariate on volume of distribution (V). The mean V of the central compartment was 7.71 (standard deviation [SD], 2.70) liters/kg of body weight, the mean elimination constant (Ke) was 0.09 (SD, 0.04) h-1, the rate constant for the caspofungin distribution from the central to the peripheral compartment was 0.44 (SD, 0.39) h-1, and the rate constant for the caspofungin distribution from the peripheral to the central compartment was 0.46 (SD, 0.35) h-1. A loading dose of 2 mg/kg on the first day, followed by 1.25 mg/kg as a maintenance dose, was chosen. With this dose, 98% of the patients were expected to reach the AUC target on the first day and 100% of the patients on the third day. The registered caspofungin dose might not be suitable for critically ill patients who were all overweight (≥120 kg), over 80% of median weight (78 kg), and around 25% of lower weight (≤50 kg). A weight-based dose regimen might be appropriate for achieving adequate exposure of caspofungin in intensive care unit patients
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