Study design of an interdisciplinary and participatory nature-based palliative rehabilitation intervention in a Danish nursing home for people with severe dementia.

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.

Diagnostic manifestations of total hemispheric glucose metabolism ratio in neuronal network diaschisis: diagnostic implications in Alzheimer's disease and mild cognitive impairment.

PURPOSE: We tested the hypothesis that lateralized hemispheric glucose metabolism may have diagnostic implications in Alzheimer's disease (AD) and mild cognitive impairment (MCI). METHODS: We performed FDG-PET/CT in 23 patients (mean age 63.7 years, range 50-78, 17 females) diagnosed with AD (n = 15) or MCI (n = 8) during a six-month period in 2014. Ten neurologically healthy individuals (HIs) (mean age 62.5 years, range 43-75, 5 females) served as controls. A neuroimaging expert provided visual assessment of diaschisis. The total hemispheric glucose metabolism ratio (THGr) was calculated, and with area-under the curve of receiver operating characteristics (AUC-ROC) we generated a "Network Diaschisis Test (NDT)". RESULTS: The qualitative detection of cerebral (Ce) and cerebellar (Cb) diaschisis was 7/15 (47%), 0/8 (0%), and 0/10 (0%) in AD, MCI, and HI groups, respectively. Median cerebral THGr was 0.68 (range 0.43-0.99), 0.86 (range 0.64-0.98), and 0.95 (range 0.65-1.00) for AD, MCI, and HI groups, respectively (p = 0.04). Median cerebellar THGr was, respectively, 0.70 (range 0.18-0.98), 0.70 (range 0.48-0.81), and 0.84 (range 0.75-0.96) (p = 0.0138). A positive NDT yielded a positive predictive value of 100% for the presence of AD or MCI and a 86% negative predictive value for healthy brain. Moreover, the diagnostic manifestation of THGr between MCI and AD led to a positive predictive value of 100% for AD, but a negative predictive value of 42.9% for MCI. CONCLUSION: Patients with AD or MCI had more pronounced diaschisis, lateralized hemispheric glucose metabolism and lower THGr compared to healthy controls. The NDT distinguished AD and MCI patients from HIs, and AD from MCI patients with a high positive predictive value and moderate and low negative predictive values. THGr can be a straightforward source of investigating neuronal network diaschisis in AD and MCI and in other cerebral diseases, across institutions.

The effect of 8 weeks of treatment with transcranial pulsed electromagnetic fields on hand tremor and inter-hand coherence in persons with Parkinson's disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02125032. Registered 29 April 2014, https://clinicaltrials.gov/ct2/show/NCT02125032?term=NCT02125032&rank=1.

The influence of posture duration on hand tremor during tasks with attention-distraction in persons with Parkinson's disease.

BACKGROUND: Tremor 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. METHOD: Fifty 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. RESULTS: Tremor 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. CONCLUSION: Tremor 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.

The Hawthorne effect as a pre-placebo expectation in Parkinsons disease patients participating in a randomized placebo-controlled clinical study.

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.

Cerebrospinal Fluid Amyloid Beta and Tau Concentrations Are Not Modulated by 16 Weeks of Moderate- to High-Intensity Physical Exercise in Patients with Alzheimer Disease.

BACKGROUND: Physical exercise may have some effect on cognition in patients with Alzheimer disease (AD). However, the underlying biochemical effects are unclear. Animal studies have shown that amyloid beta (Aß), one of the pathological hallmarks of AD, can be altered with high levels of physical activity. AIM: The objective of this study was to elucidate the effect of 16 weeks of moderate- to high-intensity physical exercise on the biomarkers of AD, with special emphasis on the amyloidogenic pathway. METHODS: From a total of 53 patients with AD participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study we analyzed cerebrospinal fluid samples for Aß species, total tau (t-tau), phosphorylated tau (p-tau) and soluble amyloid precursor protein (sAPP) species. We also assessed the patients for apolipoprotein E ε4 (ApoE ε4) genotype. RESULTS: We found no effect of 16 weeks of physical exercise on the selected biomarkers, and no effect of ApoE ε4 genotype. CONCLUSION: Our findings suggest that the possible effect of physical exercise on cognition in patients with AD is not due to modulation of Aß, t-tau, p-tau and sAPP species.

Effect of aerobic exercise on physical performance in patients with Alzheimer's disease.

INTRODUCTION: Knowledge about the feasibility and effects of exercise programs to persons with Alzheimer's disease is lacking. This study investigated the effect of aerobic exercise on physical performance in community-dwelling persons with mild Alzheimer's disease. METHODS: The single blinded multi-center RCT (ADEX) included 200 patients, median age 71 yrs (50-89). The intervention group received supervised moderate-to-high intensity aerobic exercise 1 hour × 3/week for 16 weeks. Assessments included cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy. RESULTS: Significant between-group differences in change from baseline (mean [95%CI]) favored the intervention group for cardiorespiratory fitness (4.0 [2.3-5.8] ml/kg/min, P <0.0001) and exercise self-efficacy (1.7 [0.5-2.8] points, P =0.004). Furthermore, an exercise attendance of ≥66.6% resulted in significant positive effects on single-task physical performance and dual-task performance. DISCUSSION: Aerobic exercise has the potential to improve cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy in community-dwelling patients with mild Alzheimer's disease.

Lifestyle, family history, and risk of idiopathic Parkinson disease: a large Danish case-control study.

The relationship between Parkinson disease (PD) and smoking has been examined in several studies, but little is known about smoking in conjunction with other behaviors and a family history of PD. Using unconditional logistic regression analysis, we studied individual and joint associations of these factors with idiopathic PD among 1,808 Danish patients who were diagnosed in 1996-2009 and matched to 1,876 randomly selected population controls. Although there was a downward trend in duration of smoking, this was not observed for daily tobacco consumption. A moderate intake of caffeine (3.1-5 cups/day) was associated with a lower odds ratio for PD (0.45, 95% confidence interval: 0.34, 0.62), as was a moderate intake of alcohol (3.1-7 units/week) (odds ratio = 0.60, 95% confidence interval: 0.58, 0.84); a higher daily intake did not reduce the odds further. When these behaviors were studied in combination with smoking, the odds ratios were lower than those for each one alone. Compared with never smokers with no family history of PD, never smokers who did have a family history had an odds ratio of 2.81 (95% confidence interval: 1.91, 4.13); for smokers with a family history, the odds ratio was 1.60 (95% confidence interval: 1.15, 2.23). In conclusion, duration of smoking seems to be more important than intensity in the relationship between smoking and idiopathic PD. The finding of lower risk estimates for smoking in combination with caffeine or alcohol requires further confirmation.

Cause-specific mortality among spouses of Parkinson disease patients.

BACKGROUND: Caring for a chronically ill spouse is stressful, but the health effects of caregiving are not fully understood. We studied the effect on mortality of being married to a person with Parkinson disease. METHODS: All patients in Denmark with a first-time hospitalization for Parkinson disease between 1986 and 2009 were identified, and each case was matched to five population controls. We further identified all spouses of those with Parkinson disease (n = 8,515) and also the spouses of controls (n = 43,432). All spouses were followed in nationwide registries until 2011. RESULTS: Among men, being married to a Parkinson disease patient was associated with a slightly higher risk of all-cause mortality (hazard ratio = 1.06 [95% confidence interval = 1.00-1.11]). Mortality was particularly high for death due to external causes (1.42 [1.09-1.84]) including suicide (1.89 [1.05-3.42]) and death from undefined symptoms/abnormal findings (1.25 [1.07-1.47]). Censoring at the time of death of the patient attenuated the findings for all-cause mortality in husbands (1.02 [0.95-1.09]), indicating that part of the association is with bereavement. Still, living with a person with Parkinson disease 5 years after first Parkinson hospitalization was associated with higher risk of all-cause mortality for both husbands (1.15 [1.07-1.23]) and wives (1.11 [1.04-1.17]). CONCLUSIONS: Caring for a spouse with a serious chronic illness is associated with a slight but consistent elevation in mortality risk.

Hearing Loss, Hearing Aid Use, and Risk of Dementia in Older Adults.

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.

Aerobic exercise does not affect serum neurofilament light in patients with mild Alzheimer's disease.

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.

Non-steroidal anti-inflammatory drug use and the risk of Parkinson's disease.

BACKGROUND: Experimental evidence supports a preventative role for non-steroidal anti-inflammatory drugs (NSAIDs) in Parkinson's disease (PD). METHODS: We investigated associations between use of aspirin, nonaspirin NSAIDs, and acetaminophen and PD in a large population-based case-control study using Danish health and pharmacy registries. We identified 1,931 PD cases reported in hospital or outpatient clinic records who had received a primary diagnosis of PD between 2001 and 2006, and 9,651 age- and sex-matched controls from the Danish population register. Prescription medication use was documented in a pharmacy database covering all residents of Denmark since 1995. RESULTS: Adjusting for age, sex, use of cardiovascular disease drugs, diagnosis of chronic pulmonary obstructive disorder, and Charlson comorbidity scores, and excluding prescriptions filled within 5 years before diagnosis, we found no evidence for an association between PD and either aspirin use (OR = 0.97; 95% CI 0.82, 1.14) or nonaspirin NSAID use (OR = 0.97; 95% CI 0.86, 1.09), regardless of intensity of use; further, there was no association between use of ibuprofen or acetaminophen and PD. CONCLUSION: Our findings provide no evidence for a protective effect of nonaspirin and aspirin NSAID prescription drug use shortly before PD onset.

Long-term treatment with transcranial pulsed electromagnetic fields improves movement speed and elevates cerebrospinal erythropoietin in Parkinson'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.

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 (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.

CSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes.

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.

Statin use and Parkinson's disease in Denmark.

The objective of this study was to investigate whether statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor) use is associated with risk of Parkinson's disease (PD) in Denmark. We identified 1,931 patients with a first time diagnosis of PD reported in hospital or outpatient clinic records between 2001 and 2006. We density matched to these patients 9,651 population controls by birth year and sex relying on the Danish population register. For every participant, we identified pharmacy records of statin and anti-Parkinson drug prescriptions since 1995 and before index date from a prescription medication use database for all Danish residents. Whenever applicable, the index dates for cases and their corresponding controls were advanced to the date of first recorded prescription for anti-Parkinson drugs. In our primary analyses, we excluded all statin prescriptions 2-years before PD diagnosis. Employing logistic regression adjusting for age, sex, diagnosis of chronic obstructive pulmonary disease, and Charlson comorbidity, we observed none to slightly inverse associations between PD diagnosis and statin prescription drug use. Inverse associations with statin use were only observed for short-term (

Physical Exercise May Increase Plasma Concentration of High-Density Lipoprotein-Cholesterol in Patients With Alzheimer's Disease.

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.

Associations of Motor Symptom Severity and Quality of Life to Motor Task Performance in Upper and Lower Extremities Across Task Complexity in Parkinson's Disease.

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.

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 8­isoprostane, 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, IL1ß, 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.