The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capturing of more and previously inaccessible phenomena in Parkinson disease (PD). However, more information has not translated into greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include non-compatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (in particular among vulnerable elderly patients), and the gap between the “big data” acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms enabling multi-channel data capture, sensitive to the broad range of motor and non-motor problems that characterize PD, and adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to: 1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones; 2) enhance tailoring of symptomatic therapy; 3) improve subgroup targeting of patients for future testing of disease modifying treatments; and 4) identify objective biomarkers to improve longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the Task Force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and quality of life of individuals with PD.

To assess whether selective microtubule-based vesicle transport underlies the polarized distribution of neuronal proteins, we expressed green fluorescent protein- (GFP-) tagged chimeras of representative axonal and dendritic membrane proteins in cultured hippocampal neurons and visualized the transport of carrier vesicles containing these proteins in living cells. Vesicles containing a dendritic protein, transferrin receptor (TfR), were preferentially transported into dendrites and excluded from axons. In contrast, vesicles containing the axonal protein NgCAM (neuron-glia cell adhesion molecule) were transported into both dendrites and axons. These data demonstrate that neurons utilize two distinct mechanisms for the targeting of polarized membrane proteins, one (for dendritic proteins) based on selective transport, the other (for axonal proteins) based on a selectivity "filter" that occurs downstream of transport.

Background-Clinicopathologic studies of Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) commonly reveal abnormal β-amyloid deposition in addition to diffuse Lewy bodies (α-synuclein aggregates), but the relationship among these neuropathologic features and the development of dementia in these disorders remains uncertain.

Methods:We performed detailed neuropathologic examination for 3 individuals with PDD who had PIB PET imaging within 15 months of death. Results:We observed elevated cortical uptake of [ 11 C]-PIB on in vivo PET imaging in 2 of the 3 cases. At autopsy, all 3 individuals had abundant cortical Lewy bodies (Braak PD stage 6), and were classified as low-probability Alzheimer disease (AD) based on NIA-Reagan criteria. The 2 PIB-positive individuals had abundant diffuse A␤ plaques but only sparse neuritic plaques and intermediate neurofibrillary tangle pathology. The PIB-negative individual had rare diffuse plaques, no neuritic plaques, and low neurofibrillary tangle burden. Individuals with Parkinson disease (PD) are nearly 6 times more likely to develop dementia than age-matched controls, and the majority of individuals with PD who survive more than 15 years after diagnosis will develop dementia. Conclusions:1,2 Clinicopathologic investigations have revealed heterogeneous histopathology, with Alzheimer disease (AD) pathology (amyloid plaques and neurofibrillary tangles) present in a subset of individuals with PD dementia (PDD).1 When present, AD pathology is typically found in conjunction with other neuropathologic changes, including limbic and cortical Lewy bodies and degeneration of subcortical monoaminergic and cholinergic pathways. The contribution of AD pathology to the pathogenesis of dementia in the setting of PD is thus uncertain. The presence of AD pathology has been postulated to influence clinical manifestations of dementia, for example masking features of dementia with Lewy bodies (DLB) such as hallucinations and fluctuations 3,4 or influencing the timing of dementia onset in patients with Lewy body disorders. 5Antemortem evaluation of A␤ plaque burden by PET imaging using amyloid-specific radiotracers can potentially clarify the role of these lesions in the pathogenesis of Lewy body-associated dementias (PDD and DLB). The tracer N-methyl-[11 C]2-(4Ј-methylaminophenyl)-6-hydroxybenzothiazole (or [ 11 C]-PIB for Pittsburgh Compound-B) has shown great promise for this purpose, demonstrating rapid diffusion across the blood-brain barrier, high affinity to a From the

This technology could provide insight on motor fluctuations in the context of daily life to guide clinical management and aid in development of new therapies.