Parkinson disease is an inexorably progressive neurodegenerative disorder. Multiple attempts have been made to establish therapies for Parkinson disease which provide neuroprotection or disease modification-two related, but not identical, concepts. However, to date, none of these attempts have succeeded. Many challenges exist in this field of research, including a complex multisystem disorder that includes dopaminergic and non-dopaminergic features; poorly understood and clearly multifaceted disease pathogenic mechanisms; a lack of reliable animal models; an absence of effective biomarkers of disease state, progression, and target engagement; and the confounding effects of potent symptomatic therapy. In this article, we will review previous, ongoing, and potential future trials designed to alter the progressive course of the disease from the perspective of the targeted underlying pathogenic mechanisms.
Objectives: The main purpose of this study was to investigate 4 methods of eliciting subjective cognitive complaints (SCCs) in Parkinson’s disease (PD) patients without dementia and determine the relationship between their SCC and cognitive performance. Design: This study was a retrospective analysis of a prospective cohort study. Setting: Six North American movement disorder clinics. Measurements: SCCs were elicited through a modified Neurobehavioral Inventory administered to patients and close contacts, a general complaint question, and Movement Disorders Society Unified Parkinson's Disease Rating Scale item question 1.1 administered to patients. Clinical evaluation, formal neuropsychological testing and Disability Assessment for Dementia were conducted in Ontario state. Agreement between SCCs eliciting methods was calculated. Associations between SCC, cognitive testing, and mild cognitive impairment (MCI) were assessed. Results: Of 139 participating nondemented PD patients, 42% had PD-MCI at baseline. Agreement between SCC eliciting methods was low. Neither patient-reported nor close contact-reported SCCs were associated with impaired baseline cognitive testing or PD-MCI nor were they associated with cognitive decline over time. In PD patients with normal baseline cognition, 26% of patients with 1-year follow-up and 20% of patients with 2-year follow-up met MCI criteria. Conclusions: Agreement between SCC eliciting methods is poor and no SCC method was associated with cognitive testing or decline over time. With no clear superior method for eliciting SCCs, clinicians should consider performing regular screening.
BACKGROUND AND PURPOSE: Woodhouse-Sakati syndrome is a rare autosomal recessive disorder characterized by hypogonadism, alopecia, diabetes mellitus, and progressive extrapyramidal signs. The disease is caused by biallelic pathogenic variants in the DCAF17 gene. The purpose of this study was to describe the spectrum of brain MR imaging abnormalities in Woodhouse-Sakati syndrome. MATERIALS AND METHODS: We reviewed brain MR images of 26 patients with a clinical and genetic diagnosis of Woodhouse-Sakati syndrome (12 males, 14 females; age range, 16-45 years; mean age, 26.6 years). Follow-up studies were conducted for 6 patients. RESULTS: All patients had abnormal MR imaging findings. The most common abnormalities were a small pituitary gland (76.9%), pronounced basal ganglia iron deposition (73%), and white matter lesions in 69.2%. White matter lesions showed frontoparietal and periventricular predominance. All white matter lesions spared subcortical U-fibers and were nonenhanced. Prominent perivascular spaces (15.3%) and restricted diffusion in the splenium of the corpus callosum (7.6%) were less frequent findings. Follow-up studies showed expansion of white matter lesions with iron deposition further involving the red nucleus and substantia nigra. Older age was associated with a more severe degree of white matter lesions (P Ͻ .001). CONCLUSIONS: Small pituitary gland, accentuated iron deposition in the globus pallidus, and nonenhancing frontoparietal/periventricular white matter lesions were the most noted abnormalities seen in our cohort. The pattern and extent of these findings were observed to correlate with older age, reflecting a possible progressive myelin destruction and/or axonal loss. The presence of pituitary hypoplasia and white matter lesions can further distinguish Woodhouse-Sakati syndrome from other neurodegenerative diseases with brain iron accumulation subtypes. ABBREVIATIONS: NBIA ϭ neurodegenerative diseases with brain iron accumulation; WSS ϭ Woodhouse-Sakati syndrome; SNHL ϭ sensorineural hearing loss
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