Fear: A conceptual analysis and philosophical therapy

Fear is a critical emotion in everyday life as it permeates many of our minor and major decisions. Explicitly or implicitly, fear is one of the emotions that most strongly shape human life. In this thesis fear and its philosophical remedies will be analysed through the work of western philosophers and thinkers selected based on their overall contributions in conceptualizing fear and suggesting therapies for reducing its more damaging effects. The study will show how Epicurus, Cicero and Seneca considered fear as the main obstacle in achieving peace of mind, and their ethical systems were primarily focused on dealing with this emotion by proposing eclectic philosophical therapies. Montaigne presented a humanist therapy of fear instrumented as a critical self-analysis. In contrast, a reductionist trend in thinking about fear emerged during the 17th century with the growth of materialistic philosophy. Thomas Hobbes reduced fear into a necessary tool for social control, whereas René Descartes demoted fear to a secondary emotion enacted by a dualist mechanism. This trend continued with William James’s conception of fear as a sensory-somatic reflex, and with Sigmund Freud’s hypothesis of a neurotic fear resulting from universal unconscious laws. I will also discuss how current neuroscience has reduced fear to decontextualized neural changes, and how the dominant trend in psychiatry has reified anxiety into arbitrary nomenclatures of unclear validity. On a completely different tack Ludwig Wittgenstein provided a broad ‘perspicuous presentation’ of fear, but his nuanced analysis has been largely ignored in philosophical studies. Overall it can be seen that, in keeping with the scientific revolution, the influential perspectives throughout the philosophical history of fear change from understandings that philosophy itself and reason are the best therapies for fear towards the medicalization of fear that is dominant today. By following these specific and diverse historical convergences, however, their criss-crossing insights and oversights, the thesis aims to enhance the conceptual understanding of fear and the variety of perspectives and therapies available for accommodating its enduring influence in our lives

Parkinson's disease motor subtypes and mood

Parkinson's disease is heterogeneous, both in terms of motor symptoms and mood. Identifying associations between phenotypic variants of motor and mood subtypes may provide clues to understand mechanisms underlying mood disorder and symptoms in Parkinson's disease. A total of 513 patients were assessed using the Hospital Anxiety and Depression Scale, and separately classified into anxious, depressed, and anxious-depressed mood classes based on latent class analysis of a semistructured interview. Motor subtypes assessed related to age-of-onset, rate of progression, presence of motor fluctuations, lateralization of motor symptoms, tremor dominance, and the presence of postural instability and gait symptoms and falls. The directions of observed associations tended to support previous findings with the exception of lateralization of symptoms, for which there were no consistent or significant results. Regression models examining a range of motor subtypes together indicated increased risk of anxiety in patients with younger age-of-onset and motor fluctuations. In contrast, depression was most strongly related to axial motor symptoms. Different risk factors were observed for depressed patients with and without anxiety, suggesting heterogeneity within Parkinson's disease depression. Such association data may suggest possible underlying common risk factors for motor subtype and mood. Combined with convergent evidence from other sources, possible mechanisms may include cholinergic system damage and white matter changes contributing to non-anxious depression in Parkinson's disease, while situational factors related to threat and unpredictability may contribute to the exacerbation and maintenance of anxiety in susceptible individuals

A Novel Assessment and Profiling of Multidimensional Apathy in Alzheimer's Disease

BACKGROUND: Apathy is a complex multidimensional syndrome frequently reported in Alzheimer's disease (AD) and is associated with impaired awareness. Here we present a psychometrically robust method to profile apathy in AD.  OBJECTIVES: To determine the validity and reliability of a multidimensional apathy measure, the Dimensional Apathy Scale (DAS), and explore the apathy subtype profile and its associations in AD.  METHODS: 102 people with AD and 55 healthy controls were recruited. Participants completed the DAS, the Apathy Evaluation Scale (AES), Geriatric Depression Short form (GDS-15), and Lawton Instrumental Activities of Daily Living (LIADL). Psychometric properties of the DAS were determined. AD-Control comparison was performed to explore group differences on the DAS. Latent Class Analysis (LCA) was used to explore the profile of apathy in AD.  RESULTS: The DAS had a good to excellent Cronbach's standardized alpha (self-rated = 0.85, informant/carer-rated = 0.93) and good convergent and divergent validity against standard apathy (AES) and depression (GDS-15) measures. Group comparison showed people with AD were significantly higher for all apathy subtypes than controls (p < 0.001), and lacking in awareness over all apathy subtype deficits. LCA showed three distinct AD subgroups, with 42.2% in the Executive-Initiation apathy, 28.4% in the Global apathy, and 29.4% in the Minimal apathy group.  CONCLUSIONS: The DAS is a psychometrically robust method of assessing multidimensional apathy in AD. The apathy profiles in AD are heterogeneous, with additional specific impairments relating to awareness dependent on apathy subtype

Atypical antipsychotic therapy in Parkinson's disease psychosis: A retrospective study.

ObjectiveParkinson's disease psychosis (PDP) is a frequent complication of idiopathic Parkinson's disease (iPD) with significant impact on quality of life and association with poorer outcomes. Atypical antipsychotic drugs (APDs) are often used for the treatment of PDP; however, their use is often complicated by adverse drug reactions (ADRs). In this study, we present patients with PDP who were treated with the most commonly used atypical antipsychotic agents and review their respective ADRs.MethodsA retrospective study was carried out to include a total of 45 patients with iPD who visited a movement disorders clinic between 2006 and 2015. All PDP patients treated with atypical APDs were included in the analysis for their specific ADRs.ResultsForty-five iPD patients (mean age of onset: 62.67&nbsp;±&nbsp;9.86&nbsp;years) were included, of those 10 patients had psychosis (mean age of onset: 76.80&nbsp;±&nbsp;4.61&nbsp;years). Of the 45 patients, 22.2% were found to have psychotic symptoms, of whom 70% had hallucinations, 20% had delusions, and 10% illusions. Seventy percent of psychotic symptoms occurred after ten or more years from diagnosis of iPD. PDP patients were treated with quetiapine, olanzapine, and risperidone separately or in combination, all of which were found to have certain ADRs.LimitationsThis study was limited by its retrospective study design and small sample size and with likely selection bias.ConclusionsThe prevalence of PDP is relatively high in older patients with iPD. The uses of the currently available atypical APDs in this patient population are often complicated by ADRs. The selective 5-HT 2A&nbsp;inverse agonist, pimavanserin, could be a better alternative in the treatment of PDP

Therapeutic effects of drug switching between acetylcholinesterase inhibitors in patients with Alzheimer's disease

AIM: To evaluate the therapeutic effects of switching from one acetylcholinesterase inhibitor (ChEI), donepezil, galantamine or rivastigmine, to another in Alzheimer's disease patients. METHODS: We retrospectively enrolled 171 Alzheimer's disease patients, whose ChEI medication was changed. The patients were evaluated on three major aspects of dementia - cognitive, affective and activities of daily living (ADL) measures - at 6 months (M) before the drug switch, at the time of drug switch (baseline), and at 3 M and 6 M after the drug switch. RESULTS: The doses of the three ChEI were significantly lower at 6 M after the switch compared with the pre-switch doses. Improvements in apathy were found at 3 M when switching from donepezil to galantamine, but not to rivastigmine, but this switch had adverse effects on ADL. Improvements in cognitive scores at 3 M were also found when switching from galantamine to rivastigmine, but not to donepezil. However, both of these changes improved Abe's Behavioral and Psychological Symptoms of Dementia scores (ABS), except ADL. Switching from rivastigmine to donepezil worsened ABS at 6 M, but preserved cognitive and ADL scores. CONCLUSIONS: The present study suggests that despite a relatively lower dose of ChEI after the switch, switching from donepezil or rivastigmine preserved cognitive functions for at least 6 M. Switching from galantamine to rivastigmine improved Mini-Mental State Examination and ABS at 3 M, but did not improve ADL scores. Geriatr Gerontol Int 2017; 17: 1843-1848

Elevated 5hmC levels characterize DNA of the cerebellum in Parkinson’s disease

5-methylcytosine and the oxidation product 5-hydroxymethylcytosine are two prominent epigenetic variants of the cytosine base in nuclear DNA of mammalian brains. We measured levels of 5-methylcytosine and 5-hydroxymethylcytosine by enzyme-linked immunosorbent assay in DNA from post-mortem cerebella of individuals with Parkinson’s disease and age-matched controls. 5-methylcytosine levels showed no significant differences between Parkinson’s disease and control DNA sample sets. In contrast, median 5-hydroxymethylcytosine levels were almost twice as high (p < 0.001) in both male and female Parkinson’s disease individuals compared with controls. The distinct epigenetic profile identified in cerebellar DNA of Parkinson’s disease patients raises the question whether elevated 5-hydroxymethylcytosine levels are a driver or a consequence of Parkinson’s disease

Depression rating scales in Parkinson's disease: critique and recommendations.

Depression is a common comorbid condition in Parkinson’s disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), Hospital Anxiety and Depression Scale (HADS), Zung Self-Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery-As-berg Depression Rating Scale (MADRS), Unified Parkinson’s Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES-D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer-rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM-D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES-D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham-D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time-consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted

High rates of parkinsonism in adults with autism

Abstract Background While it is now recognized that autism spectrum disorder (ASD) is typically a life-long condition, there exist only a handful of systematic studies on middle-aged and older adults with this condition. Methods We first performed a structured examination of parkinsonian motor signs in a hypothesis-generating, pilot study (study I) of 19 adults with ASD over 49 years of age. Observing high rates of parkinsonism in those off atypical neuroleptics (2/12, 17 %) in comparison to published population rates for Parkinson’s disease and parkinsonism, we examined a second sample of 37 adults with ASD, over 39 years of age, using a structured neurological assessment for parkinsonism. Results Twelve of the 37 subjects (32 %) met the diagnostic criteria for parkinsonism; however, of these, 29 subjects were on atypical neuroleptics, complicating interpretation of the findings. Two of eight (25 %) subjects not taking atypical neuroleptic medications met the criteria for parkinsonism. Combining subjects who were not currently taking atypical neuroleptic medications, across both studies, we conservatively classified 4/20 (20 %) with parkinsonism. Conclusions We find a high frequency of parkinsonism among ASD individuals older than 39 years. If high rates of parkinsonism and potentially Parkinson’s disease are confirmed in subsequent studies of ASD, this observation has important implications for understanding the neurobiology of autism and treatment of manifestations in older adults. Given the prevalence of autism in school-age children, the recognition of its life-long natural history, and the recognition of the aging of western societies, these findings also support the importance of further systematic study of other aspects of older adults with autism