Capgras Syndrome in Advanced Parkinson's Disease.

Psychosis is common in Parkinson's disease (PD), especially in advanced disease, and can lead to a number of psychotic symptoms, including delusions. One uncommon delusion is Capgras syndrome (CS). The authors report on three PD patients with a history of deep brain stimulation (DBS) who developed this delusion.

Relationship of age of onset and family history in Parkinson disease.

Background: The aim of this study was to determine whether age of onset of Parkinson disease (PD) is associated with differences in PD risk and PD age of onset in parents and siblings.

Methods: Clinical and detailed family history data were available for 1,114 PD probands.

Results: Proband age of onset was not associated with differences in PD prevalence or PD age of onset in parents.

Mortality in levodopa-treated Parkinson's disease.

Parkinson's disease (PD) is associated with increased mortality despite many advances in treatment. Following the introduction of levodopa in the late 1960's, many studies reported improved or normalized mortality rates in PD. Despite the remarkable symptomatic benefits provided by levodopa, multiple recent studies have demonstrated that PD patients continue to die at a rate in excess of their peers.

Differential susceptibility to motor impulsivity among functional subtypes of Parkinson's disease.

Background And Objectives: Parkinson's disease patients with predominant postural instability and gait difficulties (PIGD) may experience unique cognitive difficulties compared to patients with tremor predominant (TD) symptoms. PIGD patients are also at high risk for falling, and some of the worst fallers seem to react impulsively to their environment. We tested the hypothesis that PIGD patients show poorer control over motor impulses compared to TD patients.

The risky business of dopamine agonists in Parkinson disease and impulse control disorders.

Risk-taking behavior is characterized by pursuit of reward in spite of potential negative consequences. Dopamine neurotransmission along the mesocorticolimbic pathway is a potential modulator of risk behavior. In patients with Parkinson's disease (PD), impulse control disorder (ICD) can result from dopaminergic medication use, particularly dopamine agonists (DAA).

Handedness and motor symptom asymmetry in Parkinson's disease.

Background: The objective of this study was to confirm whether an association between handedness and the side of symptom onset exists and to evaluate the impact of this association on specific clinical characteristics of Parkinson's disease (PD).

Methods: 1173 PD patients were identified from a clinical database. Patients with asymmetrical onset (n=1015) were divided into those with dominant-side onset and those with non-dominant-side onset, and the clinical characteristics of the two subgroups were compared.

The effect of speed-accuracy strategy on response interference control in Parkinson's disease.

Studies that used conflict paradigms such as the Eriksen Flanker task show that many individuals with Parkinson's disease (PD) have pronounced difficulty resolving the conflict that arises from the simultaneous activation of mutually exclusive responses. This finding fits well with contemporary views that postulate a key role for the basal ganglia in action selection. The present experiment aims to specify the cognitive processes that underlie action selection deficits among PD patients in the context of variations in speed-accuracy strategy.

Autosomal dominant subcortical gliosis presenting as frontotemporal dementia.

Objective: To describe a multigenerational kindred with a frontotemporal dementia clinical syndrome (FTDS), extensive subcortical gliosis pathology, and autosomal dominant genetics.

Methods: Clinical, imaging, and pathologic evaluations of multiple family members.

Results: Symptom onset commonly occurred in the fifth or sixth decade, although some kindred members did not develop obvious symptoms until their eighth decade.

The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study.

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.

The effect of Parkinson's disease on interference control during action selection.

Basal ganglia structures comprise a portion of the neural circuitry that is hypothesized to coordinate the selection and suppression of competing responses. Parkinson's disease (PD) may produce a dysfunction in these structures that alters this capacity, making it difficult for patients with PD to suppress interference arising from the automatic activation of salient or overlearned responses. Empirical observations thus far have confirmed this assumption in some studies, but not in others, due presumably to considerable inter-individual variability among PD patients.

Huntington CAG repeat size does not modify onset age in familial Parkinson's disease: the GenePD study.

The ATP/ADP ratio reflects mitochondrial function and has been reported to be influenced by the size of the Huntington disease gene (HD) repeat. Impaired mitochondrial function has long been implicated in the pathogenesis of Parkinson's disease (PD), and therefore, we evaluated the relationship of the HD CAG repeat size to PD onset age in a large sample of familial PD cases. PD affected siblings (n = 495), with known onset ages from 248 families, were genotyped for the HD CAG repeat.

Replication of association between ELAVL4 and Parkinson disease: the GenePD study.

Genetic variants in embryonic lethal, abnormal vision, Drosophila-like 4 (ELAVL4) have been reported to be associated with onset age of Parkinson disease (PD) or risk for PD affection in Caucasian populations. In the current study we genotyped three single nucleotide polymorphisms in ELAVL4 in a Caucasian study sample consisting of 712 PD patients and 312 unrelated controls from the GenePD study. The minor allele of rs967582 was associated with increased risk of PD (odds ratio = 1.

Haplotypes and gene expression implicate the MAPT region for Parkinson disease: the GenePD Study.

Background: Microtubule-associated protein tau (MAPT) has been associated with several neurodegenerative disorders including forms of parkinsonism and Parkinson disease (PD). We evaluated the association of the MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition, postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat isoforms of MAPT, and neighboring genes Saitohin (STH) and KIAA1267, are altered in PD cerebellum.

Validity, sensitivity and specificity of the mentation, behavior and mood subscale of the UPDRS.

Objective: The unified Parkinson's disease rating scale (UPDRS) is the most widely used tool to rate the severity and the stage of Parkinson's disease (PD). However, the mentation, behavior and mood (MBM) subscale of the UPDRS has received little investigation regarding its validity and sensitivity. Three items of this subscale were compared to criterion tests to examine validity, sensitivity and specificity.

G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy.

Multiple system atrophy (MSA) is characterized clinically by Parkinsonism, cerebellar dysfunction, and autonomic impairment. Multiple mutations in the LRRK2 gene are associated with parkinsonian disorders, and the most common one, the G2019S mutation, has been found in approximately 1% of sporadic cases of Parkinsonism. In a well-characterized cohort of 136 subjects with probable MSA and 110 neurologically evaluated control subjects, none carried the G2019S mutation.

Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age: the GenePD Study.

Background: Polymorphisms in the glutathione S-transferase pi gene (GSTP1), encoding GSTP1-1, a detoxification enzyme, may increase the risk of Parkinson disease (PD) with exposure to pesticides. Using the GenePD Study sample of familial PD cases, we explored whether GSTP1 polymorphisms were associated with the age at onset of PD symptoms and whether that relation was modified by exposure to herbicides.

Methods: Seven single-nucleotide polymorphisms (SNPs) were genotyped and tested for association with PD onset age in men in three strata: no exposure to herbicides, residential exposure to herbicides, and occupational exposure to herbicides.

Preliminary FMRI evidence of visual system dysfunction in Parkinson's disease patients with visual hallucinations.

Using functional magnetic resonance imaging (fMRI), the authors examined visual cortex function in Parkinson's disease patients who did and did not experience visual hallucinations. Patients with visual hallucinations demonstrated increased activation in the visual association cortex and deficits in the primary visual cortex, suggesting that visual hallucinations are associated with an abnormality of visual-cortex function.

Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study.

Background: The PARK2 gene at 6q26 encodes parkin, whose inactivation is implicated in an early-onset autosomal recessive form of Parkinson disease (PD).

Objective: To evaluate the influence of heterozygosity for parkin mutation on onset age in a sample of families with at least 2 PD-affected members.

Design: Clinical and genetic study.

Optimizing the ongoing search for new treatments for Parkinson disease: using futility designs.

Many agents are being considered for treatment of Parkinson disease (PD). Given the large number of agents and the limited resources to evaluate new agents, it is essential to reduce the likelihood of advancing ineffective agents into large, long-term Phase III trials. Futility design methodology addresses this goal.