What contributes to depression in Parkinson's disease?

Background: Depression is a common problem in patients with Parkinson's disease, but its mechanism is poorly understood. It is thought that neurochemical changes contribute to its occurrence, but it is unclear why some patients develop depression and others do not. Using a community-based sample of patients with Parkinson's disease, we investigated the contributions of impairment, disability and handicap to depression in Parkinson's disease. Methods: Ninety-seven patients seen in a population-based study on the prevalence of Parkinson's disease completed the Beck Depression Inventory (BDI). Clinical and historical information on symptoms and complications of Parkinson's disease were obtained from the patients by a neurologist. In addition, clinician and patient ratings of disability on the Schwab and England scale were obtained and a quality of life questionnaire was completed. Results: Moderate to severe depression (BDI [gt-or-equal, slanted] 18) was reported by 19·6% of the patients. Higher depression scores were associated with advancing disease severity, recent self-reported deterioration, higher akinesia scores, a mini-mental score of 50% of the variance of depression scores. Conclusions: Depression in patients with Parkinson's disease is associated with advancing disease severity, recent disease deterioration and occurrence of falls. Regression analysis suggests that depression in Parkinson's disease is more strongly influenced by the patients' perceptions of handicap than by actual disability. The treatment of depression should therefore be targeted independently of treatment of the motor symptoms of Parkinson's disease, and consider the patients' own perception of their disease

Adolescent and Adult Children of Parents with Parkinson's Disease: Incorporating Their Needs in Clinical Guidelines

Purpose. To compare the quality of life (QoL) and emotional well-being of the offspring of parents with Parkinson's disease (PD) and multiple sclerosis (MS) and to consider results in light of current UK clinical guidelines. Methods. 143 adolescent and adult children of parents with PD and MS were postally administered the Parental Illness Impact Scale and a measure of emotional well-being. Results. Minimal differences were observed between the two groups in both QoL and emotional well-being. Levels of mild to moderate depression were substantially greater than those of the general population. Conclusions. The nonsignificant differences reported indicate a similar degree of impact across the two conditions assessed. A significant body of evidence demonstrates the considerable impact of parental MS, with the needs of children being acknowledged in current clinical guidelines. There is a need to similarly acknowledge the potential impact of parental Parkinson's in UK guidelines for PD

Why do patients with Parkinson's disease fall? A cross-sectional analysis of possible causes of falls.

Background: Falls in Parkinson’s disease (PD) are associated with significant injury, disability, hospitalization, and reduced quality of life. Aims: To identify modifiable medical causes of falls in a cohort of PD patients. Methods: Eighty seven PD patients were interviewed and examined using validated scales assessing motor and nonmotor aspects of PD, comorbidities and medication use. The frequency of falls in the last month was the primary outcome measure. Falls were hypothesized to be associated with increasing age, advanced motor severity, particularly axial features (e.g., freezing and postural instability), and dyskinesia. Nonmotor features hypothesized to be associated with falls included; cognitive impairment, psychosis, sleep disorders, cardiovascular dysfunction, and ophthalmological and medical comorbidities. Results: Fallers had longer disease duration, higher Levodopa-equivalent doses, greater ‘On’ time with dyskinesia (all P<0.005), and higher scores on some Movement Disorder Society-Unified Parkinson’s Disease Rating Scale items, particularly axial scores. However, patients with falls did not differ from non-fallers in age or overall motor UPDRS scores. Severity of psychosis, executive cognitive impairment, autonomic (particularly cardiovascular) dysfunction and sleep disturbances (particularly REM sleep behavioral disorder) were significantly associated with falls (all P<0.005). Fallers more frequently reported use of antidepressants (both tricyclics and SSRIs) and neuroleptics (P<0.001), but not hypnotics. There was no difference in medical comorbidities, ophthalmological assessments, fatigue, and apathy scores between the groups. In logistic regression analysis, cardiovascular dysfunction, antidepressant use, and REM sleep behavioral disorder were significantly associated with falls. Conclusions: The causes of falls in PD are multifactorial and extend beyond motor impairment and dyskinesia; addressing these in patients already treated with dopaminergic medications has the potential to improve this important complication of PD

Mild Parkinsonian Signs: A Systematic Review of Clinical, Imaging, and Pathological Associations

Mild parkinsonian signs (MPS) have been widely studied during the past 3 decades and proposed as a risk marker for neurodegenerative disease. This systematic review explores the epidemiology, clinical and prognostic associations, radiological features, and pathological findings associated with MPS in older adults free from neurodegenerative disease. We find that MPS as currently defined are strongly associated with increasing age and increased risk of development of Parkinson's disease (PD), all-cause dementia, disability, and death. Positive associations with later PD are found mainly in younger populations and those with other features of prodromal PD. There are currently no consistent radiological findings for MPS, and pathological studies have shown that MPS, at least in the oldest old, are often underpinned by mixed neuropathologies, including those associated with Alzheimer's disease, cerebrovascular disease, nigral neuronal loss, and Lewy bodies. Different subcategories of MPS appear to convey varying risk and specificity for PD and other outcomes. MPS overall are not specific for parkinsonian disorders and, although associated with increased risk of PD, can reflect multiple pathologies, particularly in older individuals. “Mild motor signs” appears a more appropriate term to avoid prognostic and pathological implications, and larger future studies to prospectively examine outcomes and associations of specific MPS subcategories are required

Orthostatic Hypotension and Antiparkinsonian Drugs: A Systematic Review and Meta-analysis

BACKGROUND: Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available. RESULTS: Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]). CONCLUSIONS: Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH

Macromodel-based simulation and measurement of the dynamic pull-in of viscously damped RF-MEMS switches

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An absolute reference frame for clumped isotope thermometry

Analysis of multiply substituted isotopologues of molecules (‘clumped isotope geochemistry’) presents special challenges to both precision and accuracy. Previous discussions have focused on mass spectrometric precision for these rare species and intralaboratory reference frames. This discipline has spread, demanding interlaboratory standardization. We present a four-laboratory study of the calibration of mass-47 anomalies (Δ_(47) values) in CO_2 (especially extracted from carbonate). We consider: instrument linearity, source fragmentation/recombination reactions (which vary between mass spectrometers and with time and instrument settings), and differences in methods, materials and conditions for sample preparation. We address these problems by developing a method for standardizing Δ_(47) measurements to an absolute reference frame based on theoretical predictions of the abundances of multiply-substituted isotopologues of gaseous CO_2 that has reached a thermodynamic equilibrium at a known temperature. By analyzing CO_2 gases that have been subjected to established laboratory procedures known to promote isotopic equilibration (i.e., heated gases and water-equilibrated CO_2), and by reference to the statistical thermodynamic predictions of equilibrium isotopic distributions, it is possible to construct an empirical transfer function that can then be applied to CO_2 samples with unknown Δ_(47) values. This reference frame may be unique in that it is based on thermodynamic equilibrium, rather than the isotopic composition of an arbitrary reference material. We describe the protocol necessary to construct such a reference frame, the method for converting gases with unknown clumped isotope compositions to this frame, and suggest a protocol for ensuring that reported Δ_(47) values can be compared among different laboratories, independent of laboratory-specific analytical or methodological artefacts. Application of this approach to measurements of CO_2 extracted from several carbonate reference materials results in interlaboratory agreement on their Δ_(47) values to within est. ±0.01 ‰, 1σ. Finally, we present a revised paleotemperature scale that applies when using the absolute reference frame described here, as opposed to the previous paleotemperature equation based on data from a single laboratory. More generally, this study presents a model for how interlaboratory standardization might be approached for other ‘clumped isotope’ measurements

Finite size corrections to random Boolean networks

Since their introduction, Boolean networks have been traditionally studied in view of their rich dynamical behavior under different update protocols and for their qualitative analogy with cell regulatory networks. More recently, tools borrowed from statistical physics of disordered systems and from computer science have provided a more complete characterization of their equilibrium behavior. However, the largest part of the results have been obtained in the thermodynamic limit, which is often far from being reached when dealing with realistic instances of the problem. The numerical analysis presented here aims at comparing - for a specific family of models - the outcomes given by the heuristic belief propagation algorithm with those given by exhaustive enumeration. In the second part of the paper some analytical considerations on the validity of the annealed approximation are discussed.Comment: Minor correction