Parkinson’s disease (PD) is the second most common neurodegenerative disorder, with increasing numbers of affected patients. Many patients lack adequate care due to insufficient specialist neurologists/geriatricians, and older patients experience difficulties traveling far distances to reach their treating physicians. A new option for these obstacles would be telemedicine and wearables. During the last decade, the development of wearable sensors has allowed for the continuous monitoring of bradykinesia and dyskinesia. Meanwhile, other systems can also detect tremors, freezing of gait, and gait problems. The most recently developed systems cover both sides of the body and include smartphone apps where the patients have to register their medication intake and well-being. In turn, the physicians receive advice on changing the patient’s medication and recommendations for additional supportive therapies such as physiotherapy. The use of smartphone apps may also be adapted to detect PD symptoms such as bradykinesia, tremor, voice abnormalities, or changes in facial expression. Such tools can be used for the general population to detect PD early or for known PD patients to detect deterioration. It is noteworthy that most PD patients can use these digital tools. In modern times, wearable sensors and telemedicine open a new window of opportunity for patients with PD that are easy to use and accessible to most of the population.

Symptoms of Parkinson’s disease (PD) can be controlled well, but treatment often requires expert judgment. Telemedicine and sensor-based assessments can allow physicians to better observe the evolvement of symptoms over time, in particular with motor fluctuations. In addition, they potentially allow less frequent visits to the expert’s office and facilitate care in rural areas. A variety of systems with different strengths and shortcomings has been investigated in recent years. We designed a multimodal telehealth intervention (TelePark) to mitigate the shortcomings of individual systems and assessed the feasibility of our approach in 12 patients with PD over 12 weeks in preparation for a larger randomized controlled trial. TelePark uses video visits, a smartphone app, a camera system, and wearable sensors. Structured training included setting up the equipment in patients’ homes and group-based online training. Usability was assessed by questionnaires and semi-standardized telephone interviews. Overall, 11 out of 12 patients completed the trial (5 female, 6 male). Mean age was 65 years, mean disease duration 7 years, mean MoCA score 27. Adherence was stable throughout the study and 79% for a short questionnaire administered every second day, 62% for medication confirmation, and 33% for an electronic Hauser diary. Quality of life did not change in the course of the study, and a larger cohort will be required to determine the effect on motor symptoms. Interviews with trial participants identified motivations to use such systems and areas for improvements. These insights can be helpful in designing similar trials.

Background: Parkinson disease (PD) is a neurodegenerative disorder with a variety of motor and nonmotor symptoms. Many of these symptoms can be monitored by eHealth solutions, including smartphone apps, wearable sensors, and camera systems. The usability of such systems is a key factor in long-term use, but not much is known about the predictors of successful use and preferable methods to assess usability in patients with PD. Objective: This study tested methods to assess usability and determined prerequisites for successful use in patients with PD. Methods: We performed comprehensive usability assessments with 18 patients with PD using a mixed methods usability battery containing the System Usability Scale, a rater-based evaluation of device-specific tasks, and qualitative interviews. Each patient performed the usability battery with 2 of 3 randomly assigned devices: a tablet app, wearable sensors, and a camera system. The usability battery was administered at the beginning and at the end of a 4-day testing period. Between usability batteries, the systems were used by the patients during 3 sessions of motor assessments (wearable sensors and camera system) and at the movement disorder ward (tablet app). Results: In this study, the rater-based evaluation of tasks discriminated the best between the 3 eHealth solutions, whereas subjective modalities such as the System Usability Scale were not able to distinguish between the systems. Successful use was associated with different clinical characteristics for each system: eHealth literacy and cognitive function predicted successful use of the tablet app, and better motor function and lower age correlated with the independent use of the camera system. The successful use of the wearable sensors was independent of clinical characteristics. Unfortunately, patients who were not able to use the devices well provided few improvement suggestions in qualitative interviews. Conclusions: eHealth solutions should be developed with a specific set of patients in mind and subsequently tested in this cohort. For a complete picture, usability assessments should include a rater-based evaluation of task performance, and there is a need to develop strategies to circumvent the underrepresentation of poorly performing patients in qualitative usability research.

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in situ targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS while fUS imaging revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We report a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with a brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV responses with peak CBV, activated area, and correlation coefficient increasing with the ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalized and linearly correlated with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths while the evoked hemodynamic responses colocalize and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as shedding light on one of the mechanisms behind FUS modulation, i.e., how FUS mechanically displaces brain tissue affecting cerebral hemodynamics and thereby its associated connectivity.

Aging is the biggest risk factor for Parkinson’s disease (PD) and a particular vulnerability of dopaminergic neurons in the substantia nigra to aging-associated effects has been firmly established. More recent work has revealed an important role of non-neuronal systems such as the blood-brain barrier (BBB) or the immune system in the pathogenesis of PD. Effects of aging on the immune system include a chronic inflammatory state termed inflammaging and immunosenescence. Both processes are connected to a higher pro-inflammatory potency and negatively affect the maintenance of self-tolerance. The BBB gets increasingly dysfunctional with advancing age and its endothelial cells display a more pro-inflammatory phenotype while the transport of important plasma proteins to the brain is impaired. The immune system and the BBB are heavily interdependent and are both essential for the homeostasis of especially vulnerable dopaminergic neurons. The degeneration of dopaminergic neurons can, in turn, influence the BBB or the immune system, potentially creating a vicious cycle. In this review, we aim to develop a multisystem perspective on aging and PD by incorporating the aging immune system and aging BBB into the pathophysiological processes. Given the current evidence, it seems likely that a combination of multimodal effects of aging on the levels of SN pars compacta (SNc) dopaminergic neurons, the immune system, and the BBB increase the risk of developing PD.

Background: Focused ultrasound (FUS) is an emerging non-invasive technique for neuromodulation in the central nervous system (CNS). Functional ultrasound imaging (fUSI) leverages ultrafast Power Doppler Imaging (PDI) to detect changes in cerebral blood volume (CBV), which correlate well with neuronal activity and thus hold promise to monitor brain responses to FUS. Objective: Investigate the immediate and short-term effects of transcranial FUS neuromodulation in the brain with fUSI by characterizing hemodynamic responses. Methods: We designed a setup that aligns a FUS transducer with a linear array to allow immediate subsequent monitoring of the hemodynamic response with fUSI during and after FUS neuromodulation (FUS-fUSI) in lightly anesthetized mice. We investigated the effects of varying pressures and transducer positions on the hemodynamic responses. Results: We found that higher FUS pressures increase the size of the activated brain area, as well as the magnitude of change in CBV and could show that sham sonications did not produce hemodynamic responses. Unilateral sonications resulted in bilateral hemodynamic changes with a significantly stronger response on the ipsilateral side. FUS neuromodulation in mice with a cranial window showed distinct activation patterns that were frequency-dependent and different from the activation patterns observed in the transcranial model. Conclusion: fUSI is hereby shown capable of transcranially monitoring online and short-term hemodynamic effects in the brain during and following FUS neuromodulation