Exploring the reactivity of bicyclic α-iminophosphonates to access new imidazoline I receptor ligands.

Recent studies pointed out the modulation of imidazoline I receptors (I-IR) by selective ligands as a putative strategy to face neurodegenerative diseases. Foregoing the classical 2-imidazoline/imidazole-containing I-IR ligands, we report a family of bicyclic α-iminophosphonates endowed with high affinity and selectivity upon I-IR and we advanced a representative compound B06 in preclinical phases. In this paper, we describe the synthetic possibilities of bicyclic α-iminophosphonates by exploring its ambivalent reactivity, leading to unprecedented molecules that showed promising activities as I-IR ligands in human brain tissues and good BBB permeation capabilities.

Cognitive phenotype and neurodegeneration associated with Tau in Huntington's disease.

Objective: The clinical phenotype of Huntington's disease (HD) can be very heterogeneous between patients, even when they share equivalent CAG repeat length, age, or disease burden. This heterogeneity is especially evident in terms of the cognitive profile and related brain changes. To shed light on the mechanisms participating in this heterogeneity, the present study delves into the association between Tau pathology and more severe cognitive phenotypes and brain damage in HD.

Parkinson disease psychosis: from phenomenology to neurobiological mechanisms.

Parkinson disease (PD) psychosis (PDP) is a spectrum of illusions, hallucinations and delusions that are associated with PD throughout its disease course. Psychotic phenomena can manifest from the earliest stages of PD and might follow a continuum from minor hallucinations to structured hallucinations and delusions. Initially, PDP was considered to be a complication associated with dopaminergic drug use.

Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer's Disease.

Humanity is facing a vast prevalence of neurodegenerative diseases, with Alzheimer's disease (AD) being the most dominant, without efficacious drugs, and with only a few therapeutic targets identified. In this scenario, we aim to find molecular entities that modulate imidazoline I receptors (I-IRs) that have been pointed out as relevant targets in AD. In this work, we explored structural modifications of well-established I-IR ligands, giving access to derivatives with an imidazole-linked heterocycle as a common key feature.

Measuring cognitive impairment and monitoring cognitive decline in Huntington's disease: a comparison of assessment instruments.

Background: Progressive cognitive decline is an inevitable feature of Huntington's disease (HD) but specific criteria and instruments are still insufficiently developed to reliably classify patients into categories of cognitive severity and to monitor the progression of cognitive impairment.

Methods: We collected data from a cohort of 180 positive gene-carriers: 33 with premanifest HD and 147 with manifest HD. Using a specifically developed gold-standard for cognitive status we classified participants into those with normal cognition, those with mild cognitive impairment, and those with dementia.

Parkinson's Disease-Cognitive Rating Scale (PD-CRS): Normative Data and Mild Cognitive Impairment Assessment in Brazil.

Background: The Parkinson's Disease-Cognitive Rating Scale (PD-CRS) assesses posterior-cortical and frontal-subcortical cognitive functioning and distinguishes mild cognitive impairment in Parkinson's disease (PD-MCI); however, it was not evaluated in Brazil.

Objectives: To investigate PD-CRS's reliability, validity, normative data, and accuracy for PD-MCI screening in Brazil.

Methods: The effects of age, education, and sex on PD-CRS scores were explored.

Non-Persistence of Tremorolytic Effect of Perampanel in Essential Tremor: Real-World Experience with 50 Patients.

Background: We describe our experience of using perampanel to treat essential tremor (ET) over 12 months.

Methods: We enrolled 50 ET patients in an open-label trial. Perampanel was titrated to 4 mg/day as adjuvant therapy.

Dissociable contribution of plasma NfL and p-tau181 to cognitive impairment in Parkinson's disease.

Background: Cognitive dysfunction is a disabling complication in Parkinson's disease (PD). Accuracy of diagnosis of mild cognitive impairment in PD (PD-MCI) depends on the tests performed, which limits results generalization. Blood-based biomarkers could provide additional objective information for PD-MCI diagnosis and progression.

A Functional Connectivity Study to Investigate the Role of the Right Anterior Insula in Modulating Emotional Dysfunction in Borderline Personality Disorder.

Objective: Previous imaging studies in patients with borderline personality disorder (BPD) have detected functional brain dysfunctions. Mindfulness training may improve the symptoms of BPD, although the neural mechanisms involved remain poorly understood. This study had several key aims: a) to investigate the role of right anterior insula (rAI) functional connectivity in modulating baseline emotional status in BPD, b) to compare differences in connectivity changes after mindfulness training versus interpersonal effectiveness intervention, and c) to explore the correlation between longitudinal changes in imaging data and clinical indicators.

Arithmetic Word-Problem Solving as Cognitive Marker of Progression in Pre-Manifest and Manifest Huntington's Disease.

Background: Arithmetic word-problem solving depends on the interaction of several cognitive processes that may be affected early in the disease in gene-mutation carriers for Huntington's disease (HD).

Objective: Our goal was to examine the pattern of performance of arithmetic tasks in premanifest and manifest HD, and to examine correlations between arithmetic task performance and other neuropsychological tasks.

Methods: We collected data from a multicenter cohort of 165 HD gene-mutation carriers.

Cognitive and Affective Empathy in Huntington's Disease.

Background: Empathy is a multidimensional construct and a key component of social cognition. In Huntington's disease (HD), little is known regarding the phenomenology and the neural correlates of cognitive and affective empathy, and regarding how empathic deficits interact with other behavioral and cognitive manifestations.

Objective: To explore the cognitive and affective empathy disturbances and related behavioral and neural correlates in HD.

Defective involuntary attention to novelty in type 1 diabetes and impaired awareness of hypoglycaemia.

Aim: To determine if there are differences in terms of neurophysiology and neurocognitive functioning in a group of type 1 diabetes (T1D) patients regarding hypoglycaemia awareness.

Methods: 27 patients with T1D were classified according to Clarke score as having impaired awareness of hypoglycaemia (IAH; n = 11) or normal awareness to hypoglycaemia (NAH; n = 16). We measured several clinical and sociodemographic variables and cognitive performance using neuropsychological tests.

Extrastriatal SPECT-DAT uptake correlates with clinical and biological features of de novo Parkinson's disease.

Striatal dopamine transporter (DAT) uptake assessment through I-Ioflupane Single-Pphoton Emission Computed Tomography (SPECT) provides valuable information about the dopaminergic denervation occurring in Parkinson's disease (PD). However, little is known about the clinical or biological relevance of extrastriatal DAT uptake in PD. Here, from the Parkinson's Progression Markers Initiative, we studied 623 participants (431 PD and 192 healthy controls) with available SPECT data.

Structural brain correlates of dementia in Huntington's disease.

Background: Huntington's disease (HD) is a fatal genetic neurodegenerative disorder with no effective treatment currently available. Progressive basal ganglia and whole-brain atrophy and concurrent cognitive deterioration are prototypical aspects of HD. However, the specific patterns of brain atrophy underlying cognitive impairment of different severity in HD are poorly understood.

The Free and Cued Selective Reminding Test in Parkinson's Disease Mild Cognitive Impairment: Discriminative Accuracy and Neural Correlates.

Memory alterations are common in Parkinson's disease (PD) patients but the mechanisms involved in these deficits remain poorly understood. The study aims to explore the profile of episodic memory deficits in non-demented early PD patients. We obtained neurological, cognitive and behavioral data from 114 PD patients and 41 healthy controls (HC).

Autoscopic phenomena as an atypical psychiatric presentation of Huntington's disease: A case report including longitudinal clinical and neuroimaging data.

Huntington's disease (HD) is a monogenetic neurodegenerative disease prototypically characterized by the progressive presentation of motor abnormalities, cognitive deterioration and neuropsychiatric symptoms. Even when the disorder is diagnosed based on the presence of unequivocal motor symptoms, subtle cognitive and behavioral changes emerge decades before the first motor manifestations. Here we present the atypical case of a young premanifest gene-mutation carrier who developed progressive complex autoscopic phenomena (feelings of presence, out of body experience, and heautoscopic hallucinations).

Utility of the Parkinson's disease-Cognitive Rating Scale for the screening of global cognitive status in Huntington's disease.

Background: Cognitive impairment is an essential feature of Huntington's disease (HD) and dementia is a predictable outcome in all patients. However, validated instruments to assess global cognitive performance in the field of HD are lacking.

Objectives: We aimed to explore the utility of the Parkinson's disease-Cognitive Rating Scale (PD-CRS) for the screening of global cognition in HD.

Structural brain correlates of irritability and aggression in early manifest Huntington's disease.

In Huntington's disease (HD), irritability and aggressive behavior represent highly prevalent and disabling neuropsychiatric symptoms. However, their structural brain correlates have not been extensively explored. Here, we rated the severity of irritability and aggression (IAs) using the Problem Behaviors Assessment for HD (PBA-s) in 31 early HD participants.

Impaired face-like object recognition in premanifest Huntington's disease.

Progressive striatal atrophy has long been considered the pathological hallmark of Huntington's disease (HD), but is it now recognized that malfunction and degeneration of posterior-cortical territories are also prominent characteristics of the disease. The limited knowledge about the functional impact of these posterior-cortical changes could be partially attributed to the lack of sensitive measures to capture them. We hypothesized that early malfunction of specific territories of the ventral visual pathway in premanifest HD would lead to difficulties in the recognition of complex stimuli and to differences in their neurophysiological correlates.

Cognitive and behavioral assessment in Parkinson's disease.

: Cognitive impairment and behavioral disturbances are common findings in Parkinson's disease (PD). Despite initially being considered late complications of the disease, it is currently accepted that almost all PD patients will exhibit cognitive and behavioral abnormalities from the early and even the premotor stages of the disease. : The present review focuses on the cognitive profile of PD, the clinical picture of PD-MCI and dementia in PD (PDD) and the recommended methods for cognitive assessment in this population.

Mild cognitive impairment in Parkinson's disease.

Understanding on the clinical features and neural mechanisms leading to cognitive impairment and dementia in Parkinson's disease (PD) has notably increased. At time of diagnosis, nearly all PD patients present some degree of cognitive impairment not enough severe as to significantly affect functional independence. However, even mild cognitive changes have a measurable impact to functional capacity in PD.