Parkin mRNA Expression Levels in Peripheral Blood Mononuclear Cells in Parkin-Related Parkinson's Disease.

INTRODUCTION: Pathogenic variants in parkin (PRKN gene) are the second most prevalent known monogenic cause of Parkinson's disease (PD). How monoallelic or biallelic pathogenic variants in the PRKN gene may affect its transcription in patient-derived biological material has not been systematically studied. METHODS: PRKN mRNA expression levels were measured with real-time polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMCs). PBMCs were derived from PRKN-mutated PD patients (PRKN-PD) (n = 12), sporadic PD (sPD) (n = 21) and healthy controls (n = 21). Six of the PRKN-PD patients were heterozygous, four were compound heterozygous, and two were homozygous for PRKN variants. RESULTS: A statistically significant decrease in PRKN expression levels was present, compared to healthy controls and sPD, in heterozygous (P = 0.019 and 0.031 respectively) and biallelic (P < 0.001 for both) PRKN-PD. PRKN expression levels in biallelic PD patients were uniformly very low and were reduced, albeit not significantly, compared to heterozygotes. Based on receiver operating characteristic analysis, low PRKN expression levels were a sensitive and extremely specific indicator for the presence of PRKN pathogenic variants. CONCLUSIONS: Assessment of PRKN mRNA levels in PBMCs may be a useful way to screen for biallelic pathogenic variants in the PRKN gene. Suspicion for certain variants in a heterozygous state may also be raised based on low PRKN mRNA levels. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer's Disease.

The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of NPSs at preclinical stages of cognitive decline and Alzheimer's disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at-risk state for incident cognitive impairment and is defined by the emergence of persistent NPSs among non-demented individuals in later life. These NPSs include affective dysregulation, decreased motivation, impulse dyscontrol, abnormal perception and thought content, and social inappropriateness. Accumulating evidence has recently begun to shed more light on the genetic background of MBI, focusing on its potential association with genetic factors related to AD. The Apolipoprotein E (APOE) genotype and the MS4A locus have been associated with affective dysregulation, ZCWPW1 with social inappropriateness and psychosis, BIN1 and EPHA1 with psychosis, and NME8 with apathy. The association between MBI and polygenic risk scores (PRSs) in terms of AD dementia has been also explored. Potential implicated mechanisms include neuroinflammation, synaptic dysfunction, epigenetic modifications, oxidative stress responses, proteosomal impairment, and abnormal immune responses. In this review, we summarize and critically discuss the available evidence on the genetic background of MBI with an emphasis on AD, aiming to gain insights into the potential underlying neurobiological mechanisms, which till now remain largely unexplored. In addition, we propose future areas of research in this emerging field, with the aim to better understand the molecular pathophysiology of MBI and its genetic links with cognitive decline.

Neurological Examination via Telemedicine: An Updated Review Focusing on Movement Disorders.

Patients with movement disorders such as Parkinson's disease (PD) living in remote and underserved areas often have limited access to specialized healthcare, while the feasibility and reliability of the video-based examination remains unclear. The aim of this narrative review is to examine which parts of remote neurological assessment are feasible and reliable in movement disorders. Clinical studies have demonstrated that most parts of the video-based neurological examination are feasible, even in the absence of a third party, including stance and gait-if an assistive device is not required-bradykinesia, tremor, dystonia, some ocular mobility parts, coordination, and gross muscle power and sensation assessment. Technical issues (video quality, internet connection, camera placement) might affect bradykinesia and tremor evaluation, especially in mild cases, possibly due to their rhythmic nature. Rigidity, postural instability and deep tendon reflexes cannot be remotely performed unless a trained healthcare professional is present. A modified version of incomplete Unified Parkinson's Disease Rating Scale (UPDRS)-III and a related equation lacking rigidity and pull testing items can reliably predict total UPDRS-III. UPDRS-II, -IV, Timed "Up and Go", and non-motor and quality of life scales can be administered remotely, while the remote Movement Disorder Society (MDS)-UPDRS-III requires further investigation. In conclusion, most parts of neurological examination can be performed virtually in PD, except for rigidity and postural instability, while technical issues might affect the assessment of mild bradykinesia and tremor. The combined use of wearable devices may at least partially compensate for these challenges in the future.

Perceptions of Patients, Caregivers, and Healthcare Professionals toward Telemedicine Use for Cognitive and Movement Disorders in the Aegean Islands, Greece: A Pilot Study of the SI4CARE European Project.

BACKGROUND: Patients with neurodegenerative diseases who live in remote areas often have limited access to specialized healthcare, and telemedicine represents a useful solution. The aim of this study was to investigate the perceptions toward the use of a specialized-tertiary telemedicine service of patients with cognitive and movement disorders, caregivers, and local healthcare professionals (HPs) in the Aegean Islands. METHODS: Data were derived from the "Specialized Outpatient Clinic of Memory, Dementia and Parkinson's disease through the National Telemedicine Network", March 2021-March 2023. The survey included 10 questions (5-point Likert scale). RESULTS: We received 64 questionnaires (25 patients, 18 caregivers, 21 HPs). Most participants positively perceived all aspects of telemedicine, including comfort (mean ± standard deviation: patients 4.5 ± 0.9, caregivers: 4.8 ± 0.5, HPs: 4.6 ± 0.7), access to specialized care (4.7 ± 0.6, 4.7 ± 0.5, 4.9 ± 0.4), number of transportations (4.6 ± 0.8, 4.6 ± 0.9, 4.8 ± 0.5), adequacy of follow-up (4.6 ± 0.7, 4.4 ± 0.8, 4.2 ± 0.7), future telemedicine selection (4.8 ± 0.4, 4.8 ± 0.4, 4.6 ± 0.6), perceived reliable medical assessment (4.7 ± 0.5, 4.6 ± 0.6, 4.3 ± 0.6), information delivery (4.7 ± 0.6, 4.6 ± 0.5, 4.4 ± 0.9), health status improvement (4.6 ± 0.7, 4.6 ± 0.6, 4.0 ± 0.7), cost (4.6 ± 1, 4.6 ± 1, 5.0 ± 0.2), and general satisfaction (4.8 ± 0.4, 4.7 ± 0.5, 4.5 ± 0.6). The commonest recommendations were more frequent visits, medical specialties, and dissemination of information. CONCLUSIONS: The positive perception of participants highlights the value of telemedicine for specialized healthcare for neurodegenerative disorders, especially in remote areas.