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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