Survival is reduced in GBA carriers compared to noncarriers; this seems to be partially independent from the increased risk for early dementia. The risk for dementia is strongly modulated by type of mutation. In the clinical continuum between PD and DLB, patients with GBA mutations seem to localize midway, with carriers of severe mutations closer to DLB than to idiopathic PD. Ann Neurol 2016;80:662-673.

No abstract

We report the results of a family-based study of LRRK2 G2019S penetrance in Parkinson disease. We studied 19 families identified through the analysis of unrelated consecutive patients. The cumulative incidence of the disease was 15% at 60 years, 21% at 70 years, and 32% at 80 years. This study provides accurate estimates of G2019S penetrance by minimizing the selection bias.

No abstract

Objective Dopamine dysregulation syndrome (DDS) refers to a compulsive pattern of dopaminergic drug misuse complicating Parkinson's disease (PD). To date, few data are available on DDS risk factors, cognitive profile and long-term outcome. Methods In this retrospective case-control study, consecutive PD outpatients fulfilling criteria for DDS were assessed over a 6-year period (2005)(2006)(2007)(2008)(2009)(2010)(2011). They were compared with 70 PD cases matched for age at onset, gender and disease duration, and with 1281 subjects with motor fluctuations and dyskinesias. DDS patients and matched controls underwent extensive neuropsychological assessment. Strategies for DDS patients management and the outcome at the last follow-up visit were recorded. Results Thirty-five patients with DDS were identified, reporting history of depression, family history of PD and drug abuse, greater difference between 'Off' versus 'On' motor symptoms compared to age-matched controls. They had younger age at onset (but not any gender difference) compared to general PD population. Cognitive profile of DDS did not show major abnormalities, including executive functions. DDS patients have been followed up for 3.2±2.1 years and remission was recorded in 40% of cases. Negative DDS outcome was significantly associated with poor caregiver supervision. Sustained remission occurred more commonly on clozapine and on duodenal levodopa infusion and subthalamic nucleus deep brain stimulation (STN-DBS) than on apomorphine pump treatment. Conclusions Clinicians should be aware of risk factors predisposing to DDS. Duodenal levodopa infusion and, less consistently, STN-DBS were more commonly associated with DDS remission. Effective caregiving plays a key role in long-term behavioural outcome.

Background: We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD.

Posterior cortical atrophy (PCA) represents a degenerative disorder characterized by the development of higherorder visual deficit. 1 PCA may result from heterogeneous pathologies that make up tauopathies. An increasing number of mutations in the tau gene (microtubule-associated protein tau [MAPT]) causes a wide spectrum of clinical presentations known as frontotemporal dementia with parkinsonism linked to chromosome-17 (FTDP-17). 2 Symptomatology usually involves executive dysfunction and altered personality and behavior, with patients displaying parkinsonian features.We describe the case of a woman with PCA who further developed asymmetric motor signs. A mutation in the MAPT gene was detected, and a diagnosis of FTDP-17 was formulated. To our knowledge, this is the very first report of a patient suffering from FTDP-17 diagnosed with posterior cortical atrophy. Case ReportA 55-year-old woman started suffering in 2006 from altered perception of human faces. Initially the visual distortion was fluctuating; over the following year it became constant, and she could not recognize her husband and children by their faces anymore. She further developed visuospatial deficits, with difficulty in localizing stimuli, judging distances, or orienting herself in familiar surroundings. A first neurological examination revealed visual agnosia. She had no visual hallucinations or personality changes. Biochemical investigations and CSF analysis were normal. Her mother suffered from dementia that started when she was 80. Genetic tests for Alzheimer's disease genes (betaPP, PS1, PS2) were performed, revealing normal alleles.As the disease progressed, she developed difficulties manipulating objects with her left hand. On further neurological examination, she showed marked ocular apraxia, and she appeared to be cortically blind. Motor signs appeared and were confined to her left arm, with plastic rigidity, bradykinesia, and postural tremor; dopaminergic treatment was not tolerated.Brain magnetic resonance imaging (MRI) showed slight signal alteration in parieto-occipital white matter bilaterally without significant atrophy; an 18F-FDG PET brain study demonstrated decreased metabolism in the posterior parietal and occipital regions, compatible with PCA. To investigate

No abstract