Validation of the Italian version of the Parkinson's Disease- Cognitive Functional Rating Scale.

A key distinguishing factor between mild cognitive impairment (MCI) and dementia in Parkinson's disease (PD) lies in the notable decrease in functioning due to cognitive impairment. The Parkinson's Disease-Cognitive Functional Rating Scale (PD-CRFS) was developed to assess functional limitations caused by cognitive impairment, while reducing the influence of motor impairment. The aim of this multicenter study was to (i) validate the Italian version of the PD-CFRS in PD, (ii) determine optimal cut-off scores for detecting MCI and dementia in PD, (iii) compare its performances with the most established functional assessment tool (IADL). Six hundred and sixty nine PD participants were recruited from 4 Italian Movement Disorders centers (Venice, Milan, Gravedona, and Salerno). They underwent Level-II cognitive evaluation, which resulted in 282 PD-NC, 310 PD-MCI, and 77 PDD. The PD-CFRS's psychometric and clinimetric properties, applicability, and responsiveness were analyzed. The PD-CFRS showed high acceptability. Floor and ceiling effects were acceptable. It also displayed strong internal consistency (Cronbach's α = 0.738), and test-retest reliability (ICC = .854). The PD-CFRS demonstrated higher coefficient of variation to detect dysfunction in PD-MCI patients in comparison to the IADL scale (PD-CFRS 96% vs IADL 22.5%). Convergent validity with the IADL was r = - 0.638 and - 0.527 in males and females, respectively. PD-CFRS total score negatively correlated with global cognition (MoCA corrected score r = - 0.61; p < 0.001). A cut-off score > 6.5 identified PDD with a sensitivity of 90% and specificity of 88% (AUC = .959). A cut-off value of > 1 detected PD-MCI with a sensitivity of 68% and specificity of 69% (AUC = .695). The Italian version of the PD-CFRS demonstrated to be an easy, valid and reliable tool that properly captures functional impairment due to cognitive decline in PD. It also proved to be particularly effective in the advanced stages of PD, and would be a useful support for the diagnosis of PD-MCI and PDD.

Genetic mutations in Parkinson's disease: screening of a selected population from North-Eastern Italy.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder with a multifactorial pathogenesis. Several genetic variants increase the risk of PD and about 5-10% of cases are monogenic. This study aims to define the genetic bases and clinical features of PD in a cohort of patients from Northeastern Italy, a peculiar geographical area previously not included in genetic screenings. METHODS: Using an NGS multigenic panel, 218 PD patients were tested based on age at onset, family history and development of atypical features. RESULTS: A total of 133 genetic variants were found in 103 patients. Monogenic PD was diagnosed in 43 patients (20% of the cohort); 28 (12.8%) carried mutations in GBA1, 10 in LRRK2 (4.6%) and 5 in PRKN (2.3%). In 17% of patients the genetic defect remained of uncertain interpretation. The selection criterion "age of onset < 55 years" was a significant predictor of a positive genetic test (OR 3.8, p 0.0037). GBA1 patients showed more severe symptoms and a higher burden of motor and non-motor complications compared to negative patients (dyskinesias OR 3, sleep disturbances OR 2.8, cognitive deficits OR 3.6; p < 0.05), with greater autonomic dysfunction (COMPASS-31 score 34.1 vs 20.2, p 0.03). CONCLUSIONS: Applying simple clinical criteria for genetic testing allows to increase the probability to identify patients with monogenic PD and better allocate resources. This process is critical to widen the understanding of disease mechanisms and to increase the individuation of patients potentially benefitting from future disease-modifying therapies.

Non-Motor Symptoms in Primary Familial Brain Calcification.

Background/Objectives: Primary Familial Brain Calcification is a rare neurodegenerative disorder of adulthood characterized by calcium deposition in the basal ganglia and other brain areas; the main clinical manifestations include movement disorders, mainly parkinsonism. Non-motor symptoms are not well defined in PFBC. This work aims at defining the burden of non-motor symptoms in PFBC. Methods: A clinical, genetic and neuropsychological evaluation of a cohort of PFBC patients, COMPASS-31 scale administration. Results: A total of 50 PFBC patients were recruited; in 25, the genetic test was negative; 10 carried mutations in SLC20A2 gene, 8 in MYORG, 3 in PDGFB, 1 in PDGFRB, 2 in JAM2 (single mutations), and one test is still ongoing. The main motor manifestation was parkinsonism. Headache was reported in 26% of subjects (especially in PDGFB mutation carriers), anxiety or depression in 62%, psychosis or hallucinations in 10-12%, sleep disturbances in 34%; 14% of patients reported hyposmia, 32% constipation, and 34% urinary disturbances. A neuropsychological assessment revealed cognitive involvement in 56% (sparing memory functions, to some extent). The COMPASS-31 mean score was 20.6, with higher sub-scores in orthostatic intolerance and gastrointestinal problems. MYORG patients and subjects with cognitive decline tended to have higher scores and bladder involvement compared to other groups. Conclusions: The presence of non-motor symptoms is frequent in PFBC and should be systematically assessed to better meet patients' needs.