BACKGROUND:Previous studies of the use of transcranial pulsed electromagnetic fields (T-PEMF) as a treatment for Parkinson's disease (PD) for a short period have shown positive results. The aim was to investigate the effect of long-term treatment with T-PEMF on tremor quantified by forearm muscle activation and hand acceleration in PD. METHODS:Patients (n = 14) received three 8-week periods of daily T-PEMF treatment (±50 V, 3 ms, 55 Hz, 30 min/day). Furthermore, a control group with PD (n = 8, no treatment) and a healthy reference group (n = 5) participated. The participants performed a postural task (3x1min) sitting with arms extended, horizontal, and parallel. Electrophysiological (surface electromyography (EMG) theta-band power in the tremor frequency area, 4-8 Hz) and kinematic tremor (accelerometer tremor intensity, 3-9 Hz) analyses were performed at baseline, week 17 and week 27. FINDINGS:At baseline, the PD patients (n = 22, all patients) had consistently significantly higher levels of EMG theta-band power and tremor intensity in the most affected side compared to the healthy reference group. The T-PEMF treatment decreased the median EMG theta-band power (most affected side) consistently, with a statistically significant decrease in flexor muscles and a tendency in extensor muscles. Furthermore, the T-PEMF-treatment decreased median tremor intensity statistically (both sides). In contrast, the PD control group did not change statistically (most affected side) from baseline to week 27. INTERPRETATION:Long-term treatment with T-PEMF changed forearm EMG power and hand acceleration in the tremor frequency spectrum towards healthy values. Thus, the present results add further knowledge to the effects of T-PEMF treatment in PD.

Dementia is estimated to affect 55 million people worldwide. Alzheimer's disease is the most common cause of dementia, but a variety of other conditions can also cause dementia. In this case report, we present a patient who experienced severe cognitive deterioration over 3 months. When we saw her at our clinic, she could barely remember her birthday, had trouble finding words, suffered from apraxia, was very tired, and her personality had changed. She was immediately hospitalized, and scan revealed dural arteriovenous fistula. The fistula was closed with endovascular surgery, and the patient regained most of her cognitive function.

Importance Hearing loss has been suggested as a risk factor for dementia, but there is still a need for high-quality research to better understand the association between these 2 conditions and the underlying causal mechanisms and treatment benefits using larger cohorts and detailed data. Objective To investigate the association between hearing loss and incident dementia, as well as how hearing aid use contributes to this association. Design, Setting, and Participants This population-based cohort study was conducted in Southern Denmark between January 2003 and December 2017 and included all residents 50 years and older. We excluded all persons with dementia before baseline as well as those who did not live in the region 5 years before baseline, with incomplete address history, or who had missing covariate information. Exposures Individual hearing status based on the Hearing Examinations in Southern Denmark database, which contains data on all pure-tone audiometry examinations performed at public hearing rehabilitation clinics in Southern Denmark. Main Outcomes and Measures Incident cases of dementia and Alzheimer disease as identified from national registries. Results The study population comprised 573 088 persons (298 006 women [52%]; mean [SD] age, 60.8 [11.3] years) with 23 023 cases of dementia and mean (SD) follow-up of 8.6 (4.3) years. Having a hearing loss was associated with an increased risk of dementia, with an adjusted hazard ratio (HR) of 1.07 (95% CI, 1.04-1.11) compared with having no hearing loss. Severe hearing loss in the better and worse ear was associated with a higher dementia risk, with an HR of 1.20 (95% CI, 1.09-1.32) and 1.13 (95% CI, 1.06-1.20), respectively, compared with having no hearing loss in the corresponding ear. Compared with people without hearing loss, the risk of dementia was higher among people with hearing loss who were not using hearing aids than those who had hearing loss and were using hearing aids, with HRs of 1.20 (95% CI, 1.13-1.27) and 1.06 (95% CI, 1.01-1.10), respectively. Conclusions and Relevance The results of this cohort study suggest that hearing loss was associated with increased dementia risk, especially among people not using hearing aids, suggesting that hearing aids might prevent or delay the onset and progression of dementia. The risk estimates were lower than in previous studies, highlighting the need for more high-quality longitudinal studies.

Introduction Aerobic exercise has been shown to modify Alzheimer pathology in animal models, and in patients with multiple sclerosis to reduce neurofilament light (NfL), a biomarker of neurodegeneration. Objective To investigate whether a 16-week aerobic exercise program was able to reduce serum NfL in patients with mild Alzheimer’s disease (AD). Methods This is a secondary analysis of data from the multi-center Preserving Cognition, Quality of Life, Physical Health, and Functional Ability in Alzheimer’s disease: The Effect of Physical Exercise (ADEX) study. Participants were randomized to 16 weeks of moderate intensity aerobic exercise or usual care. Clinical assessment and measurement of serum NfL was done at baseline and after the intervention. Results A total of 136 participants were included in the analysis. Groups were comparable at baseline except for APOEε4 carriership which was higher in the usual care group (75.3 versus 60.2%; p = 0.04). There was no effect of the intervention on serum NfL [intervention: baseline NfL (pg/mL) 25.76, change from baseline 0.87; usual care: baseline 27.09, change from baseline −1.16, p = 0.09]. Conclusion The findings do not support an effect of the exercise intervention on a single measure of neurodegeneration in AD. Further studies are needed using other types and durations of exercise and other measures of neurodegeneration. Clinical trial registration clinicaltrials.gov, identifier NCT01681602.

Background A limited amount of research has examined how nature-based palliative rehabilitation can be implemented in nursing homes for people with dementia, even though evidence suggests that these gardens are underused. This paper will present the study protocol of an intervention study co-designed in an interdisciplinary collaboration with a nursing home for people with dementia, to develop a tailored nature-based palliative rehabilitation program to increase qualified use of garden with the purpose of promoting a range of health outcomes. Methods The study is a single-cased quasi-experimental mixed methods study. The intervention will be developed, designed, and implemented in collaboration with the nursing home, using different co-design tools and methods. The effect of the intervention will be evaluated using the The Neuropsychiatric Inventory Nursing Home version in combination with medication use, a survey on staff burnout, and cameras in the garden to register garden use. A process evaluation with single- and focus group interviews consisting of various stakeholders in the study will be used to gain knowledge on the intervention processes and implementation. Discussion The paper presents new approaches in the field of palliative rehabilitation for people with dementia using nursing home gardens, through interdisciplinary collaboration, participatory co-design approach and mixed methods design. Using both effect and process evaluation, the study will provide unique insights in the role and importance of participatory process, interdisciplinary collaboration, and tailoring palliative rehabilitation activities in gardens at nursing homes to local needs and wishes. These results can be used to guide other nursing homes and renewal projects in the future. Trial registration ISRCTN, ISRCTN14095773 . Registered 15 July 2022—Retrospectively registered.

To identify markers in the CSF of multiple sclerosis (MS) subtypes, we used a two-step proteomic approach: (i) Discovery proteomics compared 169 pooled CSF from MS subtypes and inflammatory/degenerative CNS diseases (NMO spectrum and Alzheimer disease) and healthy controls. (ii) Next, 299 proteins selected by comprehensive statistics were quantified in 170 individual CSF samples. (iii) Genes of the identified proteins were also screened among transcripts in 73 MS brain lesions compared to 25 control brains. F-test based feature selection resulted in 8 proteins differentiating the MS subtypes, and secondary progressive (SP)MS was the most different also from controls. Genes of 7 out these 8 proteins were present in MS brain lesions: GOLM was significantly differentially expressed in active, chronic active, inactive and remyelinating lesions, FRZB in active and chronic active lesions, and SELENBP1 in inactive lesions. Volcano maps of normalized proteins in the different disease groups also indicated the highest amount of altered proteins in SPMS. Apolipoprotein C-I, apolipoprotein A-II, augurin, receptor-type tyrosine-protein phosphatase gamma, and trypsin-1 were upregulated in the CSF of MS subtypes compared to controls. This CSF profile and associated brain lesion spectrum highlight non-inflammatory mechanisms in differentiating CNS diseases and MS subtypes and the uniqueness of SPMS.

OBJECTIVE:To investigate the association between long term residential exposure to road traffic and railway noise and risk of incident dementia. DESIGN:Nationwide prospective register based cohort study. SETTING:Denmark. PARTICIPANTS:1 938 994 adults aged ≥60 years living in Denmark between 1 January 2004 and 31 December 2017. MAIN OUTCOME MEASURES:Incident cases of all cause dementia and dementia subtypes (Alzheimer's disease, vascular dementia, and Parkinson's disease related dementia), identified from national hospital and prescription registries. RESULTS:The study population included 103 500 participants with incident dementia, and of those, 31 219 received a diagnosis of Alzheimer's disease, 8664 of vascular dementia, and 2192 of Parkinson's disease related dementia. Using Cox regression models, 10 year mean exposure to road traffic and railway noise at the most (Ldenmax) and least (Ldenmin) exposed façades of buildings were associated with a higher risk of all cause dementia. These associations showed a general pattern of higher hazard ratios with higher noise exposure, but with a levelling off or even small declines in risk at higher noise levels. In subtype analyses, both road traffic noise and railway noise were associated with a higher risk of Alzheimer's disease, with hazard ratios of 1.16 (95% confidence interval 1.11 to 1.22) for road Ldenmax ≥65 dB compared with <45 dB, 1.27 (1.22 to 1.34) for road Ldenmin ≥55 dB compared with <40 dB, 1.16 (1.10 to 1.23) for railway Ldenmax ≥60 dB compared with <40 dB, and 1.24 (1.17 to 1.30) for railway Ldenmin ≥50 dB compared with <40 dB. Road traffic, but not railway, noise was associated with an increased risk of vascular dementia. Results indicated associations between road traffic Ldenmin and Parkinson's disease related dementia. CONCLUSIONS:This nationwide cohort study found transportation noise to be associated with a higher risk of all cause dementia and dementia subtypes, especially Alzheimer's disease.

Background Parkinson’s disease is characterized by motor dysfunctions including bradykinesia. In a recent study, eight weeks of daily transcranial stimulation with bipolar pulsed electromagnetic fields improved functional rate of force development and decreased inter-hand tremor coherence in patients with mild Parkinson’s disease. Objective To investigate the effect of long-term treatment with transcranial bipolar pulsed electromagnetic fields on motor performance in terms of movement speed and on neurotrophic and angiogenic factors. Methods Patients diagnosed with idiopathic Parkinson’s disease had either daily 30-min treatment with bipolar (±50 V) transcranial pulsed electromagnetic stimulation (squared pulses, 3ms duration) for three eight-week periods separated by one-week pauses (T-PEMF group) (n = 16) or were included in a PD-control group (n = 8). Movement speed was assessed in a six-cycle sit-to-stand task performed on a force plate. Cerebrospinal fluid and venous blood were collected and analyzed for erythropoietin and vascular endothelial growth factor. Results Major significant improvement of movement speed compared to the natural development of the disease was found (p = 0.001). Thus, task completion time decreased gradually during the treatment period from 10.10s to 8.23s (p<0.001). The untreated PD-control group did not change (p = 0.458). The treated group did not differ statistically from that of a healthy age matched reference group at completion of treatment. Erythropoietin concentration in the cerebrospinal fluid also increased significantly in the treated group (p = 0.012). Conclusion Long-term treatment with transcranial bipolar pulsed electromagnetic fields increased movement speed markedly and elevated erythropoietin levels. We hypothesize that treatment with transcranial bipolar pulsed electromagnetic fields improved functional performance by increasing dopamine levels in the brain, possibly through erythropoietin induced neural repair and/or protection of dopaminergic neurons.

Background: Multiple sclerosis (MS) is characterized by different degree of inflammatory and neurodegenerative features in the early relapsing vs. progressive subtypes. By using controls with different extent of inflammation vs. neurodegeneration, we examined the CSF proteome to identify molecular markers that differentiate between subtypes of MS. Gene expression of specific proteins were explored in MS brain lesions with diverse pathological background. Methods: (i) First, we compared the proteome by LC-MS/MS in 169 pooled CSF from MS subtypes to inflammatory/degenerative controls: AQP4-IgG-positive and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD), Alzheimer’s disease (AD), and healthy controls. F-test based feature selection was used to cluster diseases and MS subtypes. (ii) Next, we selected 299 molecules by comprehensive statistics, and quantified them in the individual CSF samples. (iii) We also screened the genes of MS-specific CSF proteins in transcriptomes of 73 MS brain lesions with different pathology. Results: We identified 11 proteins that separated diseases, and 8 proteins that clustered MS subtypes. Secondary progressive (SP)MS had the most unique proteome characterized by upregulation of intrinsic pathway proteins of the coagulation pathway. SPMS also clustered far from NMOSD indicating less inflammatory pathways. Primary progressive (PP)MS was more similar to relapsing-remitting (RR)MS than SPMS. Quantification of 299 proteins in 170 individual CSF samples identified 5 molecules uniquely upregulated in MS subtypes and in AQP4-IgG-positive NMOSD, respectively. Chitinase-3-like protein 1 (CHI3L1) was upregulated in part of PPMS and remission CSF samples, and it was expressed by astrocytes in chronic active lesions. GFAP was upregulated in 70% of AQP4-IgG-positive NMOSD but only in 40% of AQP4-IgG-negative NMOSD. Conclusions: By the combination of untargeted and targeted quantitative analysis, we identified CSF molecular markers of axonal growth inhibition, lipid binding, and protein/lipid transport that differentiated between neuroinflammatory and neurodegenerative diseases, and also MS subtypes. The majority of them were expressed in MS brain lesions suggesting their origin from the brain tissue and not from the systemic compartment. Data suggest that the CSF proteome of SPMS is different from PPMS, and astrocyte damage may not be major pathology in part of the AQP4-IgG seronegative NMOSD.

Lifestyle factors have been shown to increase the risk of developing Alzheimer's disease (AD) later in life. Specifically, an unfavorable cholesterol profile, and insulin resistance are associated with increased risk of developing AD. One way to non-pharmacologically affect the levels of plasma lipids is by exercise, which has been shown to be beneficial in cognitively healthy individuals. In this randomized controlled trial y, we therefore aimed to clarify the effect of physical exercise on the lipid profile, insulin and glucose in patients with AD. In addition, we investigated the effect of apolipoproteinE genotype on total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) in plasma from patients with AD. Plasma samples from 172 patients who underwent 16 weeks of moderate-to-high intensity exercise (n= 90) or treatment as usual (n= 82) were analyzed change from baseline for the levels of total cholesterol, LDL-C, HDL-C, TG, glucose, and insulin. In addition, we analyzed those from the exercise group who adhered to the protocol with an attendance of 2/3 or more of the exercise session and who followed the protocol of an intensity of 70% of the maximum heart rate. We found a significant increase in plasma HDL-C levels between the "high exercise sub-group" compared to control group. After intervention HDL-C was increased by 4.3% in the high-exercise group, and decreased by 0.7% in the control group, after adjustment for statin use. In conclusion, short term physical activity may be beneficial on the cholesterol profile in patients with AD.

Parkinson’s disease (PD) tremor comprises asymmetric rest and postural tremor with unilateral onset. Tremor intensity can be amplified by stress and reduced by attention, and the medical treatment is complex. Mirror movements and unintentional synchronization of bimanual movements, possibly caused by insufficient inhibition of inter-hemispheric crosstalk, have been reported in PD, indicating a lag of lateralization. Potential neuroprotective effects of pulsed electromagnetic fields (PEMF) have been reported in-vitro and in rodents, as have influences of PEMF on human tremor. The aim was to investigate the effect of 8 weeks daily transcranial PEMF treatment (T-PEMF) of persons with PD on rest and postural hand tremor characteristics and on inter-hand coherence. Hand accelerations of 50 PD participants with uni- or bilateral tremor participating in a clinical trial were analysed. A rest and postural tremor task performed during serial subtraction was assessed before and after 8 weeks of T-PEMF (30 min/day, 50 Hz, ±50 V, 3 ms squared pulses) or placebo treatment (sham stimulation 30 min/day). Forty matched healthy persons (no treatment) were included as reference. Intensity and inter-hand coherence related measures were extracted. The T-PEMF treatment decreased the inter-hand coherence in the PD group with unilateral postural tremor. The PD group with unilateral postural tremor was less clinically affected by the disease than the PD group with bilateral postural tremor. However, no differences between T-PEMF and placebo treatment on either intensity related or coherence related measures were found when all persons with PD were included in the analyses. The peak power decreased and the tremor intensity tended to decrease in both treatment groups. Eight weeks of T-PEMF treatment decreased inter-hand coherence in the PD group with unilateral postural tremor, while no effects of T-PEMF treatment were found for the entire PD group. The unilateral postural tremor group was less clinically affected than the bilateral postural tremor group, suggesting that early treatment initiation may be beneficial. In theory, a reduced inter-hand coherence could result from a neuronal treatment response increasing inter-hemispheric inhibition. However, this requires further studies to determine. Studies of even longer treatment periods would be of interest. ClinicalTrials.gov , NCT02125032. Registered 29 April 2014, https://clinicaltrials.gov/ct2/show/NCT02125032?term=NCT02125032&rank=1

BackgroundTremor is one of the hallmarks and most bothersome symptoms in Parkinson's disease (PD). The classical PD tremor is present at rest, but postural tremor also occurs. PD tremor can be continuous or intermittently present and can have a re-emergent nature. The tremor intensity is affected by attention and stress level. Observations of PD tremor have indicated increased tremor intensity with time during 30-s tremor assessments. This phenomenon has not previously been studied systematically. Thus, in order to contribute to our understanding of the mechanisms associated with PD tremor, our aim was to investigate the influence of time during a posture holding and a resting task on hand tremor characteristics in persons with PD compared to healthy peers.MethodFifty persons with PD and at least one tremoring hand (tremor intensity exceeding mean+2SD of a healthy reference group (REF), N=40) were included from a clinical trial population. Hand accelerations in a rest and postural condition were measured in 30-s assessments while the participants performed a self-paced simple subtraction task with eyes closed to standardize attention without inducing stress. Tremor intensity, maximal power, frequency of maximal power and tremor onset time was calculated for three consecutive 10-s time intervals.ResultsTremor intensity and maximal power increased significantly during the 30-s recording in the PD-group in both conditions (1st-3rd time-interval, tremor intensity: rest +65% p<0.0001, postural +55% p<0.0001; maximal power: rest +93% p<0.0001, postural +82% p<0.001). No effect of time was found on frequency of maximal power in the PD-group or on any effect measure in the REF-group.ConclusionTremor intensity and maximal power increased with time in the PD-group during 30-s tasks, while no change with time was found in the REF-group. In contrast, frequency of maximal power remained unchanged, which may suggest that the same neural circuits were responsible for the tremor generation throughout the tasks. The increase in tremor intensity and maximal power could not solely be explained by re-emergence of tremor. This suggests an increasing or gradually more synchronized cortico-spinal drive throughout the tasks. However, this requires further studies to determine.

Our group has completed an exercise study of 200 patients with mild Alzheimer's disease. We found improvements in cognitive, neuropsychiatric, and physical measures in the participants who adhered to the protocol. Epidemiological studies in healthy elderly suggest that exercise preserves cognitive and physical abilities to a higher extent in AP OE ε4 carriers. In this post hoc subgroup analysis study, we investigated whether the beneficial effect of an exercise intervention in patients with mild AD was dependent on the patients' APOE genotype. We found that patients who were APOE ε4 carriers benefitted more from the exercise intervention by preservation of cognitive performance and improvement in physical measures. This exploratory study establishes a possible connection between the beneficial effects of exercise in AD and the patients' APOE genotype. These findings, if validated, could greatly impact the clinical management of patients with AD and those at risk for developing AD.

We tested the hypothesis that lateralized hemispheric glucose metabolism may have diagnostic implications in Alzheimer’s disease (AD) and mild cognitive impairment (MCI).

BACKGROUND:Neuroinflammation is recognized as part of the pathological progression of Alzheimer's disease (AD), but the molecular mechanisms are still not entirely clear. Systemically, physical exercise has shown to have a positive modulating effect on markers of inflammation. It is not known if this general effect also takes place in the central nervous system in AD. The aim of this study was to investigate the effect of 16 weeks of moderate to high-intensity physical exercise on selected biomarkers of inflammation both systemically and in the CNS, in patients with AD. METHODS:Plasma and cerebrospinal fluid (CSF) from 198 patients with Alzheimer's disease participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study were analyzed for concentrations of 8‑isoprostane, soluble trigger receptor expressed on myeloid cells 2 (sTREM2), and the MSD v-plex proinflammation panel 1 human containing interferon gamma (IFNγ), Interleukin-10 (IL10), IL12p70, IL13, IL1β, IL2, IL4, IL6, IL8, and tumor necrosis factor alpha (TNFα), before and after a 16-week intervention with physical exercise, and we studied whether changes were modulated by the patients' APOE genotype. RESULTS:Most inflammatory markers remained unchanged after exercise. We found an increasing effect of 16 weeks of physical exercise on sTREM2 measured in CSF. Further, IL6 in plasma increased in the exercise group after physical exercise (mean relative change 41.03, SD 76.7), compared to controls (-0.97, SD 49.4). In a sub-analysis according to APOE genotype, we found that in ε4 carriers, exercise had a stabilizing effect on IFNγ concentration with a mean relative change of 7.84 (SD 42.6), as compared to controls (114.7 (SD 188.3), p = 0.038. CONCLUSION:Our findings indicate an effect of physical exercise on markers of neuroinflammation in CSF measured by an increase in sTREM2 in patients with AD. Further, there may be a small inflammatory systemic effect related to physical exercise in patients with AD.

The authors examined the associations between the performance of upper- and lower-extremity motor tasks across task complexity and motor symptom severity, overall disease severity, and the physical aspects of quality of life in persons with Parkinson’s disease. The performance was assessed for three lower-extremity tasks and two upper-extremity tasks of different levels of complexity. The motor symptoms and overall disease severity correlated significantly with all motor tasks with higher correlation coefficients in the complex tasks. Thus, the strength of the association between disease severity or severity of motor symptoms and motor performance is task-specific, with higher values in complex motor tasks than in simpler motor tasks. Mobility-related and activity-of-daily-living-related quality of life correlated with lower-extremity tasks of low and medium complexity and with the complex upper-extremity task, respectively; this suggests that Parkinson’s Disease Questionnaire-39 is capable of differentiating between the impact of gross and fine motor function on quality of life.

Introduction: Brain imaging studies in healthy elderly subjects suggest a positive effect of aerobic exercise on both brain structure and function, while the effects of aerobic exercise in Alzheimer's Disease (AD) has been scarcely investigated. Methods: In a single-blinded randomized MRI study, we assessed the effects of an aerobic exercise intervention on brain volume as measured by magnetic resonance imaging (MRI) and its correlation to cognitive functioning in patients with AD. The study was a sub-study of a larger randomized controlled trial (ADEX study). Forty-one patients were assigned to a control or exercise group. The exercise group performed 60-min of aerobic exercise three times per week for 16 weeks. All participants underwent whole-brain MRI at 3 Tesla and cognitive assessment at baseline and after 16 weeks. Attendance and intensity were monitored providing a total exercise load. Changes in regional brain volumes and cortical thickness were analyzed using Freesurfer software. Results: There was no effect of the type of intervention on MRI-derived brain volumes. In the entire group with and without training, Exercise load showed a positive correlation with changes in volume in the hippocampus, as well as frontal cortical thickness. Volume changes in frontal cortical thickness correlated with changes in measures of mental speed and attention and exercise load in the exercise group. Conclusion: We did not find evidence to support an effect of 16 weeks of aerobic exercise on brain volume changes in patients with AD. Longer intervention periods may be needed to affect brain structure as measured with volumetric MRI. Clinical Trial registration: ClinicalTrials.gov Identifier: NCT01681602, registered September 10th, 2012 (Retrospectively registered).

Background: The Hawthorne effect on clinical studies in Parkinson's disease has not been thoroughly investigated. Evidently the Hawthorne effect may have impact on study outcomes acting as a pre-placebo' effect in the recruitment phase, hence before inclusion.Aim: The aim of this study was to discuss the Hawthorne effect in relation to clinical and self-reported outcome measures in a randomized clinical study in the recruitment phase and during the study.Methods: Data from 97 participants with Parkinson's disease treated with Transcranial Pulsed Electromagnetic Fields were applied, randomized to an active (n=49) or a placebo treated group (n=48). The participants received one home treatment session, for eight consecutive weeks. Outcome measures were the Unified Parkinson's Disease Rating Scale, The 39-item Parkinson's Disease Questionnaire and the WHO-5.Results: No difference in treatment effect between the two groups was found pertaining the Unified Parkinson's Disease Rating Scale. No difference in treatment effect between the two groups was found pertaining the 39-item Parkinson's Disease Questionnaire, apart from the dimension mobility. No difference in treatment effect between the two groups was found pertaining the WHO-5 scale.Conclusions: The Hawthorne effect may have caused a pre-placebo' effect on the outcome measures even before obtaining baseline outcomes measures. This study may have been particularly prone to a Hawthorne effect due to the intense contact with the participants before and during the study. Moreover, the Hawthorne effect should not be viewed upon as a single entity but rather as entities affecting outcome measures throughout the full study period.

BACKGROUND:Parkinson's disease is caused by dopaminergic neurodegeneration resulting in motor impairments as slow movement speed and impaired balance and coordination. Pulsed electromagnetic fields are suggested to have neuroprotective effects, and could alleviate symptoms.OBJECTIVE:To study 1) effects of 8-week daily transcranial pulsed electromagnetic field treatment on functional rate of force development and movement speed during two motor tasks with different levels of complexity, 2) if treatment effects depend on motor performance at baseline.METHODS:Ninety-seven persons with Parkinson's disease were randomized to active transcranial pulsed electromagnetic field (squared bipolar 3 ms pulses, 50 Hz) or placebo treatment with homebased treatment 30 min/day for 8 weeks. Functional rate of force development and completion time of a sit-to-stand and a dynamic postural balance task were assessed pre and post intervention. Participants were sub-grouped in high- and low-performers according to their baseline motor performance level. Repeated measure ANOVAs were used.RESULTS:Active treatment tended to improve rate of force development during chair rise more than placebo (P = 0.064). High-performers receiving active treatment improved rate of force development during chair rise more than high-performers receiving placebo treatment (P = 0.049, active/placebo: 11.9±1.1 to 12.5±1.9 BW/s ≈ 5% / 12.4±1.3 to 12.2±1.3 BW/s, no change). No other between-treatment-group or between-treatment-subgroup differences were found. Data on rate of force development of the dynamic balance task and completion times of both motor tasks improved but did not allow for between-treatment differentiation.CONCLUSION:Treatment with transcranial pulsed electromagnetic fields was superior to placebo regarding functional rate of force development during chair rise among high-performers. Active treatment tended to increase functional rate of force development while placebo did not. Our results suggest that mildly affected persons with Parkinson's disease have a larger potential for neural rehabilitation than more severely affected persons and indicate that early treatment initiation may be beneficial.