The abnormal accumulation of copper ions is considered to be one of the pathological factors of Alzheimer's disease, but the internal relationship between Cu and Alzheimer's disease progression is still not fully clear.

In this work, a sensitive and selective near-infrared fluorescent copper ion probe was designed for quantification and visualization of Cu level in lysates, living cells, living zebrafish and brain tissues of drosophila and mice with Alzheimer's disease.

By using this probe, the authors demonstrated that the content of Cu in the brains of Alzheimer's disease mice and drosophila enhanced nearly 3.5-fold and 4-fold than that of normal mice and drosophila, respectively.

More importantly, pathogenesis analysis revealed that elevated Cu led to changes in factors closely associated with Alzheimer's disease, such as the increasing of reactive oxygen species, the aggregation of amyloid-β protein and nerve cell cytotoxicity.

These findings could promote the understanding of the roles between Cu and Alzheimer's disease.

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Prior studies have demonstrated that Lyme disease is frequently over-diagnosed. However, few studies describe which conditions are misdiagnosed as Lyme disease.

This retrospective observational cohort study evaluated patients referred for Lyme disease to a Maryland academic center between 2000-2013 who lacked evidence for Borrelia burgdorferi infection. The primary outcome is clinically described diagnoses contributing to symptoms. Secondary outcomes included symptom duration and determination whether diagnoses were new or attributed to existing medical conditions.

Of 1261 referred patients, 1061 had no findings of active Lyme disease, with 690 receiving other diagnoses.

Among the 690 patients, the median symptom duration was 796 days, and a total of 139 discrete diagnoses were made. Infectious disease diagnoses comprised only 3.2%. Leading diagnoses were anxiety/depression, fibromyalgia, chronic fatigue syndrome, migraine disorder, osteoarthritis and sleep disorder/apnea.

Examples of less frequent but non-syndromic diseases newly diagnosed included multiple sclerosis, malignancy, Parkinson's disease, sarcoidosis or amyotrophic lateral sclerosis.

Most patients with long-term symptoms have either new or pre-existing disorders accounting for their symptoms other than Lyme disease, suggesting overdiagnosis in this population. Patients referred for consideration of Lyme disease for chronic symptoms deserve careful assessment for diagnoses other than Borrelia burgdorferi infection.

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Impaired Color Discrimination in Alzheimer Disease Dementia.

- Posted by admin in English

Patients with Alzheimer disease dementia often show impaired orientation and navigation. Signage offers an opportunity to compensate for these deficits, communicate information efficiently and facilitate way finding. Certain properties of signs such as colors and contrasts may beneficially affect the uptake and processing of information particularly in ADD patients.

Thirty-six healthy older adults and 30 ADD patients performed a computerized color perception task that required discriminating different color combinations. The effects of different contrast features on performance accuracy and speed in the 2 experimental groups were examined by nonparametric mixed analysis of variances.

Analyses revealed a significant effect of contrast polarity on reaction times, significant effects of group on reaction times and errors as well as a marginally significant interaction of group×color on errors. All participants benefited from positive contrast polarity as indicated by increased performance speed. Furthermore, ADD patients reacted slower and less accurate than healthy controls, but showed higher accuracy at black-white and red-yellow than at blue-green color combinations.

The authors' findings suggest the implementation of signs with positive contrast polarity to ensure faster reactions. In addition, certain color combinations may enhance accuracy, particularly in patients with ADD.

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Mevidalen is a selective positive allosteric modulator (PAM) of the dopamine D1 receptor subtype.

The scientists objective was to assess the safety and efficacy of mevidalen for treatment of cognition in patients with Lewy body dementia (LBD).

Mevidalen resulted in significant, dose-dependent improvements of MDS-UPDRS total score. The 30 mg and 75 mg mevidalen doses significantly improved ADCS-CGIC scores compared to placebo.

Increases in blood pressure, adverse events, and cardiovascular serious adverse events were most pronounced at the 75 mg dose.

Mevidalen harnesses a novel mechanism of action that improves motor symptoms associated with Lewy body dementia on top of standard of care while improving or not worsening non-motor symptoms associated with traditional dopaminergic therapy.

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Whether multiple nutritional deficiencies have a synergic effect on mobility loss remains unknown. This study aims to evaluate associations between multi-nutritional deficits and physical performance evolution among community-dwelling older adults.

The scientists here included 386 participants from the Multidomain Alzheimer Preventive Trial not receiving omega-3 polyunsaturated fatty acid supplementation and who had available data on nutritional deficits.

Baseline nutritional deficits were defined as plasma 25 hydroxyvitamin D <20 ng/ml, plasma homocysteine >14 mol/L, or erythrocyte omega-3 PUFA index 4.87%.

The Short Physical Performance Battery, gait speed, and chair rise time were used to assess physical performance at baseline and after 6, 12, 24, 36, 48, and 60 months.

Within-group comparisons showed that physical function worsened over time, particularly in participants with 2 nutritional deficits; however, no between-group differences were observed when individuals without deficit and those with either 1 or 2 deficits were compared.

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The subthalamic nucleus (STN) is considered a key structure in motor, behavioral, and emotional control.

Although identification of the functional topography of the STN has therapeutic implications in the treatment of the motor features of Parkinson's disease, the details of its functional and somatotopic organization in humans are not well understood.

The aim of this study was to characterize the functional organization of the STN and its correlation with the motor outcomes induced by subthalamotomy.

A diffusion-weighted imaging/functional magnetic resonance imaging-driven somatotopic parcellation of the STN was defined to delineate the representation of the upper and lower limb in the STN.

Functional magnetic resonance imaging-driven parcellation demonstrated dual segregation of motor cortico-subthalamic projections in humans.

Moreover, the relationship between lesion topography and functional anatomy of the STN explains specific improvement in bradykinesia, rigidity, and tremor induced by subthalamotomy.

Identifying the functional topography of the STN will facilitate better definition of the optimal location for functional neurosurgical approaches, that is, electrode placement and lesion location, and improve specific cardinal features in Parkinson disease.

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De novo variants in QRICH1 has recently been reported in 11 individuals with intellectual disability. The function of QRICH1 is largely unknown but it is likely to play a key role in the unfolded response of endoplasmic reticulum stress through transcriptional control of proteostasis. In this study, the authors present 27 additional individuals and delineate the clinical and molecular spectrum of the individuals with QRICH1 variants. Additional findings included poor weight gain, short stature, autism spectrum disorder, seizures and scoliosis. Truncating or splice variants were found in 28 individuals and 10 had missense variants. This study confirms that heterozygous QRICH1 variants cause a neurodevelopmental disorder including short stature and expands the phenotypic spectrum to include poor weight gain, scoliosis, hypotonia, minor structural brain anomalies, and seizures. Inherited variants from mildly affected parents are reported for the first time, suggesting variable expressivity.

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Disturbances of the early stages of neurogenesis lead to irreversible changes in the structure of the mature brain and its functional impairment, including increased excitability, which may be the basis for drug-resistant epilepsy. The range of possible clinical symptoms is as wide as the different stages of disturbed neurogenesis may be. In this study, the authors used a quadruple model of brain dysplasia by comparing structural and functional disorders in animals whose neurogenesis was disturbed with a single dose of 1 Gy of gamma rays at one of the four stages of neurogenesis, i.e. Thereafter, pilocarpine was administered and significant differences in susceptibility to seizure behavioral symptoms were detected depending on the degree of brain dysplasia. Before, during and after the seizures significant correlations were found between the density of parvalbumin-immunopositive neurons located in the cerebral cortex and the intensity of behavioral seizure symptoms or increases in the power of particular EEG bands. Neurons expressing calretinin or NPY showed also dysplasia-related increases without, however, correlations with parameters of seizure intensity. The results point to significant roles of parvalbumin-expressing interneurons, and also to expression of NPY - an endogenous anticonvulsant and neuroprotectant reducing susceptibility to seizures and supporting neuronal survival. This article is protected by copyright. All rights reserved.

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The scientists here describe and validate Smile-GAN, a semi-supervised deep-clustering method, which examines neuroanatomical heterogeneity contrasted against normal brain structure, to identify disease subtypes through neuroimaging signatures. When applied to regional volumes derived from T1-weighted MRI including cognitively normal individuals and those with cognitive impairment and dementia, Smile-GAN identified four patterns or axes of neurodegeneration. Applying this framework to longitudinal data revealed two distinct progression pathways. Measures of expression of these patterns predicted the pathway and rate of future neurodegeneration. Pattern expression offered complementary performance to amyloid/tau in predicting clinical progression. These deep-learning derived biomarkers offer potential for precision diagnostics and targeted clinical trial recruitment.

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