Effects of Long-Term Treatment with T-PEMF on Forearm Muscle Activation and Motor Function in Parkinson’s Disease

Bipolar pulsed electromagnetic stimulation applied to the brain (T-PEMF) is a non-pharmacological treatment which has been shown to stimulate nerve growth, attenuate nerve abnormalities, and improve microcirculation. We report on a 62-year-old, medically well-treated man with idiopathic Parkinson’s disease. He was treated with T-PEMF, 30 min per day for three 8-week periods separated by two 1-week breaks. The disease made his handwriting impossible to read mainly due to small letters and lack of fluency. Forearm EMG measured during standardized conditions showed an involuntary spiky EMG pattern with regular burst activity (on his left side) at baseline. The intervention normalized the handwriting and forearm EMG. The UPDRS-motor score decreased from 25 to 17, and UPDRS-II-handwriting decreased from a pre-intervention value of 3 to 0 after the intervention. Finally, the patient reported improved fine motor function, less muscle stiffness, less muscle cramps and tingling, and less fatigue during the day in response to the T-PEMF treatment. The improved handwriting lasted for approximately 3 months after the treatment. Our results should be considered as preliminary, and large-scale, controlled studies are recommended to elucidate the therapeutic potential of long-term treatment with T-PEMF

Exercise as a potential modulator of inflammation in patients with Alzheimer's disease measured in cerebrospinal fluid and plasma

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

Residential exposure to transportation noise in Denmark and incidence of dementia:National cohort study

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 (L(den)max) and least (L(den)min) 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 L(den)max ≥65 dB compared with <45 dB, 1.27 (1.22 to 1.34) for road L(den)min ≥55 dB compared with <40 dB, 1.16 (1.10 to 1.23) for railway L(den)max ≥60 dB compared with <40 dB, and 1.24 (1.17 to 1.30) for railway L(den)min ≥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 L(den)min 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

Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease:A Randomized Controlled Trial

Background: Studies of physical exercise in patients with Alzheimer’s disease (AD) are few and results have been inconsistent. Objective: To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD. Methods: In a randomized controlled trial, we recruited 200 patients with mild AD to a supervised exercise group (60-min sessions three times a week for 16 weeks) or to a control group. Primary outcome was changed from baseline in cognitive performance estimated by Symbol Digit Modalities Test (SDMT) in the intention-to-treat (ITT) group. Secondary outcomes included changes in quality of life, ability to perform activities of daily living, and in neuropsychiatric and depressive symptoms. Results: The ITT analysis showed no significant differences between intervention and control groups in change from baseline of SDMT, other cognitive tests, quality of life, or activities of daily living. The change from baseline in Neuropsychiatric Inventory differed significantly in favor of the intervention group (mean: –3.5, 95% confidence interval (CI) –5.8 to –1.3, p = 0.002). In subjects who adhered to the protocol, we found a significant effect on change from baseline in SDMT as compared with the control group (mean: 4.2, 95% CI 0.5 to 7.9, p = 0.028), suggesting a dose-response relationship between exercise and cognition. Conclusions: This is the first randomized controlled trial with supervised moderate-to-high intensity exercise in patients with mild AD. Exercise reduced neuropsychiatric symptoms in patients with mild AD, with possible additional benefits of preserved cognition in a subgroup of patients exercising with high attendance and intensity.</jats:p

A 16-Week Aerobic Exercise Intervention Does Not Affect Hippocampal Volume and Cortical Thickness in Mild to Moderate Alzheimer’s Disease

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)