non motor symptoms in glucocerebrosidase-related parkinson's disease

Conditions: Parkinson Disease

Summary: the goal of this observational study is to describe non motor symptoms in a prospective study of patients with parkinson's disease associated to glucocerebrosidase (gba-pd) mutations. the main questions it aims to answer are: * do gba-pd patients have a greater burden of non motor symptoms? * how do these non motor symptoms evolve during a prospective follow up of two years? * are these non motor symptoms different from those that affect parkinson's disease patients without glucocerebrosidase mutations (non gba-pd), in prevalence, severity and type? * do these non motor symptoms correlate with objective measures such as posturography or speed reaction tests? * is there a test or combination of tests that can predict the appearance of early or severe non motor symptoms? for this reason researchers will compare the gba-pd group of patients with a group of non mutated gba parkinson disease. participants will undergo a neurological and neuropsychological evaluation with different tests in subsequent visits for a total of 2 years.

parkinson's disease is the second most prevalent neurodegenerative disorder worldwide. up to date, the main risk factor for its development is carrying an heterozygous mutation in glucocerebrosidase gene (gba). gba codifies for a gc-ase protein that takes part in lysosomal function. the homozygous mutation of this gene gives rise to gaucher disease, which is a lysosomal disorder. this gene has also been associated with lewy body dementia. the presence of an heterozygous mutation in gba in parkinson's disease can be found in up to 5-15% of the patients, depending on age and ethnicity. it has been described that those patients carrying the mutation can have an earlier debut of the disease. according to non motor symptoms, patients are prone to develop earlier and more severe motor symptoms. this has been studied specially in cognitive impairment but also dysautonomia, impulse control disorder and others. in relation to cognitive impairment these patients usually develop an earlier and more severe affection, reaching dementia states earlier in the disease. some studies have described a worsening in cognitive function in gba mutated patients after deep brain stimulation (dbs) to treat parkinsonian symptoms. this prevents patients from being candidates to therapies such as dbs. for this reason, the investigators consider it important to make a proper description of non motor symptoms in gba mutated parkinsonian patients, since this finding can help to delineate the prognosis and choose individualized treatments, regarding the suggested differences with other parkinson's disease patients. it is an observational prospective cohort study. participants will be collected from a subgroup of patients that have agreed to undertake a genetic test including a panel of genes associated to parkinson's disease. according to the results, patients will be subdivided in two groups according to their genetic status: * gba heterozygous mutations * absence of genetic mutations these patients will undergo neurologic evaluations, neuropsychological evaluations and self-administered evaluations. there will be no intervention. the pharmacologic and other type of treatment assessments will be conducted during their regular follow up with their neurologist. these visits will be repeated every 6 months for a total of 2 years. total of 5 visits for each patient.

Eligibility criteria:
inclusion criteria: * aged over 18 years old. * fulfill parkinson's disease criteria of movement disorder society 2015. * parkinson's disease symptoms began before they were 70 and/or parkinson's disease family history. * underwent a genetic test of parkinson's disease related genes. * heterozygous mutation of glucocerebrosidase gene (only cases). * absence of mutation in the parkinson's disease genetic test (only controls). exclusion criteria: * suspicion of atypical parkinsonism. * personal history of other neurodegenerative disorders such as alzheimer's disease. * personal history of significant cerebrovascular damage, intracraneal lessions or important craneoencephalic trauma. * deep brain stimulation treatment for parkinson's disease. * moderate or severe dementia that precludes from performing the tests.

Keywords: glucocerebrosidase heterozygous mutation non motor symptoms neuropsychology posturography