Mitochondrial injury: a hot spot for parkinsonism and Parkinson's disease?

The recent identification of genes (parkin, DJ-1, and PINK1) involved in recessive autosomal parkinsonism, and the indications that these proteins may have protective effects on the mitochondria, has led to the reemergence of the notion that mitochondrial dysfunction might play a central role in the etiology of sporadic Parkinson's disease (PD). This idea has previously been supported by biochemical analyses showing reduced mitochondrial activity in PD patients and in animal models of PD generated by the selective inhibition of mitochondria activity. However, the involvement of DJ-1 or PINK1 loss of function in classical idiopathic PD, characterized by pathological inclusions composed of aggregated alpha-synuclein protein, has still not been evaluated. More detailed studies of the possible interactions between parkin, DJ-1, PINK1, and alpha-synuclein and their effects on mitochondria are needed to more adequately define the biological pathways that may convergently or independently lead to parkinsonism.     

Leg-extension strength and chair-rise performance in elderly women with Parkinson's disease

The lower extremity performance in elderly female patients with mild to moderate Parkinson's disease (PD; n = 12) and controls (n = 16) was compared. Isometric dynamometry and force-plate measurements were used. PD patients had lower (p < .05) bilateral (BL) maximal isometric leg-extension force (MF), BL isometric MF relative to body mass, and maximal rate of isometric force development than control participants. BL strength deficit was greater (p < .05) in PD patients than in controls. A significantly longer chair-rise time and lower maximal rate of vertical-ground-reaction-force development while rising from a chair was found in PD patients than in controls. These findings suggest that elderly women with PD have lowered voluntary isometric force-generation capacity of the leg-extensor muscles. Reduced BL leg-extension strength might contribute to the difficulty of individuals with PD to rise from a chair.     

Prevalence of Problem and Pathological Gambling in Parkinson’s Disease

Pathological gambling (PG) has been identified in patients with Parkinson’s disease (PD) treated with dopamine agonists suggesting that dysregulation of brain dopaminergic activity may contribute to the development of gambling problems. The current study was undertaken to further establish the prevalence of problem and PG in patients with PD, identify any clinical correlates, and determine if psychiatric or substance use co-morbidity contributes to the increased prevalence of problem and PG. A cross-sectional survey of 140 serially recruited moderate to severe PD patients was undertaken utilizing the Canadian Problem Gambling Index, Alcohol Use Disorders Identification Test, Drug Abuse Screening Test, Beck Depression Inventory, Beck Anxiety Inventory, and Mini-Mental State Exam augmented by chart review, completed over an 8 month period. The 12 month prevalence of problem and PG in PD was 9.3% compared to 1.6% in the general population within a comparably aged sample. The increased prevalence of problem and PG in the PD group was related to dopamine agonist use and younger age, but not co-morbidity. Most subjects with problem and PG reported their gambling increased after being diagnosed with PD and starting treatment. The results suggest that brain dopaminergic activity is involved in the underlying neurobiology of problem and PG.     

Effectiveness of water-based exercise in people living with Parkinson’s disease: a systematic review

This systematic review summarizes the relatively scant literature concerning the effectiveness of water-based exercise (WBE) interventions in people with Parkinson’s disease (PD). Databases MEDLINE, EMBASE, PEDro, Scopus, and SportDiscus were searched from the earliest available date to December 2011. Studies had to meet the following selection criteria: (1) the target population was patients with PD; (2) the effects of a WBE intervention (as the primary intervention) were tested; (3) the abstract of the research was available in English. Selected studies were subject to unmasked quality assessment by applying a methodological scoring with a possible maximum score of 15 points. Twelve studies met the inclusion criteria, although only three of them achieved a methodological quality score above 10 points. Collectively, the data showed that WBE has some beneficial short-term effects on the impact that PD has on the patients (mainly on their motor symptoms and on their functional mobility), as well as on their quality of life. This review provides evidence that WBE is safe for patients with PD, but there is a lack of hard evidence regarding its beneficial effects. Further randomized and controlled trials with larger sample sizes are required.     

Management of Parkinson's disease in older women

Elderly women with Parkinson's disease (PD) represent a specific patient population that may benefit from individualized treatment strategies. PD has been shown to occur approximately twice as often in men than in women, resulting in theories regarding estrogen being protective against the disease and as a potential treatment strategy. Given women's longer life expectancy, they are more likely to reach an age where antiparkinsonian medications are associated with side-effects. This paper will review medical and surgical treatments as well as the relationship of gender and age with respect to the management of PD.     

Neurodegeneration in normal brain aging and disease

Normal "healthy" aging is defined as aging without disease. Many aged people do not exhibit symptoms of disease and lead normal lives, but nonetheless display pathological changes that are characteristic of Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), and/or cerebrovascular disease (CVD). These changes are restricted to distinct brain regions and might represent preclinical stages of these disorders. This Perspective discusses arguments in favor of and against the hypothesis that pathological changes related to AD, PD, DLB, and CVD in the brains of nondemented elderly people represent early stages of these diseases rather than healthy aging. We conclude that early pathological disease-related changes do indeed constitute the beginning of AD, PD, DLB, and CVD rather than normal concomitants of aging, even in the absence of any clinical symptoms. Aging is, therefore, a major risk factor for these diseases but does not necessarily lead to age-related diseases.     

Association of the modified frailty index with adverse outcomes after penile prosthesis implantation

Objectives: To investigate frailty as a predictor of surgical outcome in elderly patients undergoing penile prosthesis implantation.

Material and methods: A total of 54 elderly patients, above 60 years of age, underwent penile prosthesis implantation between 2012 and 2014. Their data were collected and retrospectively analyzed. A modified frailty index (mFI) was calculated for each patient based on 11 risk factors from the Canadian Study of Health and Aging Frailty Index. The 1-year adverse outcomes were correlated with mFI, patients’ and procedure’s risk factors.

Results: Mean age was 64.9?±?5.2 years. No mortality was reported in our patients, however, one-year adverse outcomes were encountered in 43 (79.6%) patients. Among all studied variables, the 1-year adverse outcomes was not significantly association with mFI, but with preoperative glycosylated hemoglobin A1c (HbA1c) (p?=?0.031) and associated Peyronie’s disease (PD) (p?=?0.000). HbA1c, dyslipidemia, hypertension, PD and duration of the procedure were predictive of infection complications (p?Conclusions: mFI is not a predictive of post-penile prosthesis implantation adverse outcomes in elderly patients with impotence. Degree of diabetic control and association with PD was associated with the 1-year adverse outcomes and infection complications.     

Changes in executive function after acute bouts of passive cycling in Parkinson's disease

Individuals with Parkinson's disease (PD) often experience cognitive declines. Although pharmacologic therapies are helpful in treating motor deficits in PD, they do not appear to be effective for cognitive complications. Acute bouts of moderate aerobic exercise have been shown to improve cognitive function in healthy adults. However, individuals with PD often have difficulty with exercise. This study examined the effects of passive leg cycling on executive function in PD. Executive function was assessed with Trail-Making Test (TMT) A and B before and after passive leg cycling. Significant improvements on the TMT-B test occurred after passive leg cycling. Furthermore, the difference between times to complete the TMT-B and TMT-A significantly decreased from precycling to postcycling. Improved executive function after passive cycling may be a result of increases in cerebral blood flow. These findings suggest that passive exercise could be a concurrent therapy for cognitive decline in PD.     

Parkinson's disease

In this case study, we describe the symptoms, neurological examination, test results, and brain pathology of a man with Parkinson's disease (PD). PD commonly presents with tremor or changes in one's ability to walk or move. Other major difficulties caused by this disease include rigidity of the body, slowness of movement, and postural imbalance. The disease symptoms principally result from the degeneration of a specific population of neuronal cells in the brain stem, in a region called the pars compacta of the substantia nigra. Pathology shows the loss of these cells and the appearance of characteristic neuronal cytoplasmic inclusions called Lewy bodies, which are composed principally of aggregated alpha-synuclein protein.     

Mandatory Testing of Drivers on the Basis of Age and Degenerative Diseases: Stakeholder Opinions

Concerns about the driving competence of older drivers have led to policy discussions about mandatory aged-based and disorder-based assessments. This study explored the attitudes, beliefs, and preferences of older adults, law enforcement officers, and licensing authorities toward reexamination of driving skills for persons with Alzheimer's disease (AD) and Parkinson's disease (PD) and at varying ages. With few exceptions, participants across all groups supported retesting drivers with AD. Moderate support was given for further evaluation of 90-year-olds and those with PD. Least endorsement was given for reassessment of 70-year-old drivers. Findings have implications for legislative changes to address drivers with AD and PD and at older ages.     

What to Expect: Information and the Management of Uncertainty in Parkinson's Disease

The onset of a chronic illness such as Parkinson's Disease (PD) demands an urgent response to life's fundamental questions. General practitioners (GPs) who care for people with PD may also face anxieties, but these affect their professional rather than their personal lives. However, uncertainty at whatever level requires managing. Both patients and GPs adopt various strategies to resolve their difficulties. One aspect of this process concerns coming to understand, and explaining what to expect of, the disease. Using data from in-depth interviews with people with PD and a separate group of GPs, this paper explores how the differing experience and management of uncertainty by both parties may, if unappreciated by doctors, hinder effective communication between them. Conversely, an imaginative understanding of what PD means may help transform people's experience of the illness. Training GPs to develop skills in understanding the special uncertainties of PD is considered.     

Impulse Control Disorder Behaviors Associated with Pramipexole Used to Treat Fibromyalgia

Objective: Compulsivity has been associated with use of dopamine agonists used to treat Parkinson’s disease (PD). Increasing use of these agents to treat fibromyalgia (FM) raises concern for this unexpected toxicity in a new group of patients. This is the first report of compulsive gambling and shopping among patients taking dopamine agonists for treatment of FM. Design: A retrospective chart review of all patients in a large, active FM research practice was used to identify compulsivity associated with dopamine agonists and describe its remission following dug withdrawal. Results: Of 3006 patients with FM treated between 2002 and 2006, 1356 had taken ≥1 dose of a dopamine agonist ( >95% pramipexole). Twenty-one (3 male, 18 female) were identified with compulsive gambling (33%), shopping (40%) or both (27%) after taking a 4.5 mg mean dose of pramipexole at bedtime for 14.4 ± 14.9 months. Compulsivity resolved in 3–10 days for 19 of 21 patients and by 3 months for all following a monitored, compulsory tapered discontinuation over 7 days. Conclusions: While biologic aspects of PD and FM differ considerably, compulsive gambling and shopping have become important, yet unexpected concerns related to use of dopamine agonists for patients with FM and their treating clinicians.     

Tai Chi-based exercise for older adults with Parkinson's disease: a pilot-program evaluation

The primary objective of this study was to provide preliminary evaluation of the feasibility, safety, and efficacy of a newly developed Tai Chi-based exercise program for older adults with Parkinson's disease (PD). Using a one-group pretest-posttest design, 17 community-dwelling adults (mean age 71.51 years) with mild to moderate idiopathic PD (Stage I, II, or III on the Hoehn and Yahr scale) and stable medication use completed a 5-day, 90-min/day Tai Chi exercise-evaluation program. Outcome measures included face-to-face exit interviews on appropriateness and safety and physical performance (i.e., 50-ft speed walk, up-and-go, functional reach). At the end of this brief intervention, exercise adherence was 100% and the program was shown to be safe. Exit interviews indicated that the program was well received by all participants with respect to program appropriateness, participant satisfaction and enjoyment, and intentions to continue. Furthermore, a significant pretest-to-posttest change was observed at the end of the 5-day program in all three physical-performance measures (p < .05). The results of this pilot evaluation suggest that Tai Chi is an appropriate physical activity for older adults with PD and might also be useful as a therapeutic exercise modality for improving and maintaining physical function. These preliminary findings warrant further investigation.     

Mitochondrial bioenergetics, aging, and aging-related disease

In this Perspective, the author discusses some of the bioenergetic consequences of the various alterations in mitochondrial function that have been hypothesized to be associated with human aging and aging-related disease. Special focus is afforded to neurodegenerative disease.     

Cyclin-dependent kinase 5--a neuronal killer?

In dividing cells, cyclin-dependent kinases (Cdks) are cell cycle-associated protein kinases that regulate proliferation, differentiation, senescence, and apoptosis. In neurons that no longer divide, deregulation of Cdks, especially Cdk5, occurs in many neurological disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Cdk5 is a unique member of the Cdk family because it does not play a critical role in cell cycle progression, and it is not activated by a cyclin. Instead, Cdk5 normally is activated by the regulatory protein p35. This Cdk5/p35 activity has emerged as an important regulator of proper development of the mammalian central nervous system. In vitro studies suggest that aberrant activation of Cdk5 by an endogenous truncated version (p25) of p35 might be a key event in the process of neurodegeneration. One enzyme responsible for cleavage of p35 to form p25 is calpain, a calcium-activated protease that has been shown to be involved in neuronal cell death. Recent studies provided important in vivo evidence that hyperactivation and redistribution of Cdk5 by p25 plays an essential role in the phosphorylation of "pathological" substrates (such as tau) and the cell death of neurons in experimental models of AD and PD. Because amyloid beta peptide, the primary neurotoxic component of amyloid plaques in AD, has been shown to increase the conversion of p35 to p25, aberrant activation of Cdk5 by p25 might be a pathway connecting amyloid beta toxicity to tau hyperphosphorylation in AD.     

Lessons from Drosophila models of DJ-1 deficiency

Mutations in the DJ-1 gene are associated with rare forms of autosomal recessive early-onset Parkinson's disease (PD). Although the precise physiological function of DJ-1 remains obscure, accumulating evidence suggests that DJ-1 may normally function as a redox-sensitive molecular chaperone that can protect against the deleterious effects of oxidative stress, particularly in mitochondria. Recent studies in the fruit fly, Drosophila melanogaster, have shed further light on the biological role of DJ-1. DJ-1-deficient Drosophila models exhibit distinct phenotypes but collectively highlight a prominent neuroprotective role for DJ-1 against oxidative insult. However, Drosophila lacking DJ-1 do not consistently produce a useful PD-like phenotype (that is, they generally fail to exhibit degeneration of neurons that contain the neurotransmitter dopamine), which may reflect putative compensatory neuroprotective mechanisms. DJ-1-deficient fly models further highlight the utility of Drosophila as an important tool for elucidating protein function and for modeling neurodegenerative disease.     

Physical activity, genes, and lifetime predisposition to chronic disease

This mini-review summarizes the main associations between physical activity and chronic diseases and discusses the basic concepts related to the role of genetic factors in studies evaluating the effects of physical activity/exercise therapy on chronic disease prevention/treatment during the life course. Many observational cohort studies have shown that high physical activity during young adulthood or middle age is associated with reduced later life morbidity, mobility limitations and mortality. Physical activity or exercise therapy has a positive effect on health via many disease-specific mechanisms. The most consistent finding of the various randomized controlled studies conducted to date is that aerobic/functional capacity and/or muscle strength can be improved by exercise training among patients with different chronic diseases. Genes are known to play a role in chronic disease predisposition and to contribute to physical fitness levels, physical activity participation and ageing. Physical fitness, physical activity and health outcomes may be partly due to underlying genetic factors that have a favourable effect on all these traits (genetic pleiotropy). This means that in observational studies, the relationship between baseline activity and the later occurrence of diseases may not be interpreted entirely as causal. Increased knowledge on the role of nuclear genome, mitochondrial genome, epigenetics, telomeres and regulation of gene expression will increase our understanding of their relationships with physical activity and morbidity.     

Psychological Distress in Older Portuguese Gay and Bisexual Men: The Mediating Role of LGBT Community Connectedness

Abstract

Objectives: Examining Psychological Distress (PD) among older Portuguese gay and bisexual men (GBM), and the mediator role of LGBT community connectedness (LGBTCC) of minority stress variables on PD. Methods: We performed a mediation analysis with LGBTCC as mediator between minority stress variables and PD with a sample of 110 elderly GBM. Results: We found moderate PD levels; LGBTCC was a significant mediator between concealment of sexual orientation and PD, but not between internalized stigma and expectations of rejection and PD. Conclusions: More attention is needed to Older Portuguese GBM’s mental health. LGBTCC is an important ameliorating factor for older GBM.     

Facilitating collaborative teacher learning: the role of “mindfulness” in video-based teacher professional development programs

In teacher professional development (PD), the component of collaborative participation among teachers is emphasized. Especially in video-based PD programs, the role of building up a teacher learning community and a trustful exchange among group members is important. Since general rules for productive collaboration do not exist at the beginning of a PD program, the role of a facilitator is pivotal for the successful development of a teacher learning community. In this paper, we present a new video-based PD program, the “Dialogic Video Cycle” (DVC), focusing on the improvement of classroom dialogue. In describing the DVC and the facilitation actions (“moves”), we highlight the role of the facilitator as mindful in providing teachers with new knowledge and with guiding the exchange among teachers about teaching practices and reflections. Results of a final evaluation of the program showed positive perceptions of the facilitation approach in the video-based PD program.     

Lighting,signing, showing: The circulability of Pink Dot's counterpublic discourse in Singapore

Pink Dot, a homegrown LGBTQ activist group based in Singapore, has been treated as a social movement since its inauguration in 2009, and they organise an annual event to advocate for LGBTQ individuals. In 2020, due to the coronavirus pandemic, the twelfth edition of the event (PD12) took place online as a livestream on YouTube. The highlight of PD12 was the unveiling of a ‘digital pink dot’ via a virtual map of Singapore, where the permeability of its discourse in virtual and physical spaces became much more apparent in comparison with previous physical iterations of the event. Approaching the data with counterpublic and citizenship theory, I outline the circulability of discourse as the key feature of a counterpublic, and argue that PD12 achieves this in two ways: (i) the semiotic fragmentation of its physical signs and online discourse; and (ii) the deployment of intertextual elements in a drag performance.