The relation of anxiety and cognition in Parkinson's disease

OBJECTIVE: Parkinson’s disease (PD) has long been conceptualized as a motor disorder, but nonmotor symptoms also manifest in the disease and significantly reduce quality of life. Anxiety and cognitive dysfunction are prevalent nonmotor symptoms, even in early disease stages, but the relation between these symptoms remains poorly understood. We examined self-reported anxiety and neurocognitive function, indexed by measures of executive function (set-shifting and phonemic fluency), categorical fluency, and attention/working memory. We hypothesized that anxiety would correlate with cognitive performance. METHOD: The Beck Anxiety Inventory and cognitive tests (Trail Making, Verbal Fluency, Digit Span) were administered to 77 nondemented adults with mild to moderate idiopathic PD (39 men, 38 women; Mage = 62.9 years). RESULTS: Higher anxiety was associated with more advanced disease stage and severity and with poorer set-shifting when using a derived metric to account for motoric slowing. Depression correlated with greater anxiety and disease severity, but not with cognitive performance. CONCLUSIONS: Our findings support the association of anxiety with a specific domain of executive function, set-shifting, in nondemented individuals with mild to moderate PD, raising the possibility that treatment of anxiety may alleviate aspects of executive dysfunction in this population.Accepted manuscrip

A Stage-Based Approach to Therapy in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-pharmaceutical treatments represent the best therapeutic options to improve quality of life in PD patients. The aim of the present review is to provide a practical, stage-based guide to pharmacological management of both motor and non-motor symptoms of PD. Furthermore, warning about drug side effects, contraindications, as well as dosage and methods of administration, are highlighted here, to help the physician in yielding the best therapeutic strategies for each symptom and condition in patients with PD

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset

Phenotype-, comorbidity-, and treatment-related prognostic factors in Parkinson’s disease

Parkinson’s disease (PD) is mainly a late-life neurodegenerative movement disorder.The prevalence of PD is increasing rapidly in the world. It is typically associated with an early and progressive loss of dopaminergic neurons in the substantia nigra. However, it also affects several other neurotransmitter systems making it a multisystem progressive disease. The clinical presentation of PD is variable with respect to both motor and non-motor symptoms. As the cardinal motor signs (rest tremor, rigidity, bradykinesia and postural instability) appear in a patient, substantial damage of dopaminergic neurons has already occurred. In turn, some of the nonmotor symptoms, such as constipation, psychiatric problems and sleep problems, may occur several years before motor symptoms in the prodromal phase of PD. PD is a progressive disorder that is associated with increased mortality. Although current pharmacotherapies and device-aided therapies of PD induce clear effects on the quality of life, there is a lack of evidence of which treatments could alter the course of the disease. This thesis investigated patient characteristic-, comorbidity-, and treatment-related prognostic factors of PD patients. The results demonstrated improved survival of Finnish male PD patients in recent years without a similar change in female PD patients. This will further increase the male-to-female ratio in PD prevalence. The results also showed that a previously diagnosed hyperdopaminergic schizophrenia spectrum disorder increases the risk of hypodopaminergic PD later in life. In line with previous evidence, we observed that psychosis/hallucination-, cognition-, and constipation-related problems in the early course of PD are related to worse survival of PD patients. Moreover, we found a possible novel link between pain in the prediagnostic period of PD and mortality within the first five years after diagnosis. Furthermore, the results demonstrated that the outcome of deep brain stimulation (DBS) treatment in monogenic PD patients depends on the mutated gene. The outcome of DBS seems to be excellent in patients with LRRK2 p.G2019S mutations and good in patients with PRKN mutations whereas it appears less favourable in patients with LRRK2 p.R1441G mutations. Moreover, marked progression of cognitive and neuropsychiatric symptoms in PD patients with SNCA, GBA and LRRK2 p.T2013S mutations may diminish the overall benefit of DBS in these monogenic PD patients.Ilmiasuun, yhteissairastavuuteen ja hoitoon liittyvät ennusteelliset tekijät Parkinsonin taudissa Parkinsonin tauti on pääasiassa myöhemmällä iällä ilmaantuva neurodegeneratiivinen liikehäiriö, joka on nopeimmin yleistyvä neurologinen sairaus maailmassa. Parkinsonin taudissa keskiaivojen mustatumakkeen dopaminergiset hermosolut tuhoutuvat. Tauti aiheuttaa muutoksia muissakin välittäjäainejärjestelmissä, joten sitä voidaan pitää etenevänä systeemisairautena. Parkinsonin taudin kliininen oirekuva koostuu motoristen ja ei-motoristen oireiden kokonaisuudesta. Mustatumakkeen dopaminergisissä hermosoluissa on todettavissa jo merkittävä vaurio, kun potilaalle ilmaantuu motorisia oireita. Joitakin ei-motorisia oireita, kuten ummetusta ja unihäiriöitä, voi kuitenkin ilmaantua useita vuosia aiemmin niin sanotussa Parkinsonin taudin prodromaalivaiheessa. Parkinsonin tauti on etenevä sairaus, johon liittyy lisääntynyt kuolleisuus terveisiin verrokkihenkilöihin nähden. Nykyisten lääke- ja laitehoitojen avulla saadaan vaikutettua positiivisesti potilaiden elämänlaatuun, mutta taudin etenemistä hidastavaa tai pysäyttävää hoitomuotoa ei ole vielä saatavilla. Tässä väitöskirjassa tutkittiin potilaiden ilmiasuun, yhteissairastavuuteen ja hoitoon liittyviä ennusteellisia tekijöitä Parkinsonin taudissa. Tulokset osoittivat, että Suomessa diagnosoitujen Parkinson-potilaiden elinajanennuste on kasvanut miehillä naisia enemmän, mikä tulee kasvattamaan jo nyt yliedustettua miesten osuutta Parkinson-potilaissa. Tulokset osoittivat myös, että potilaalla aiemmin diagnosoitu hyperdopaminerginen skitsofrenia lisää myöhemmin kehittyvän hypodopaminergisen Parkinsonin taudin riskiä. Aiempia tutkimustuloksia vastaten havaitsimme taudin alkuvaiheessa esiintyvien psykoosi-, kognitio- ja ummetusoireiden liittyvän huonompaan ennusteeseen Parkinsonin taudissa. Lisäksi havaitsimme ennen diagnoosia esiintyvän kipuoireiston mahdollisen yhteyden korkeampaan kuolleisuuteen viiden vuoden sisällä Parkinsondiagnoosin asettamisesta. Tulokset osoittivat myös, että syväaivostimulaation vaste perinnöllisessä Parkinsonin taudissa riippuu taudinaiheuttajamutaatiosta. Hoitovaste vaikuttaa olevan erinomainen potilailla, joilla on LRRK2-geenin p.G2019S-mutaatio tai PRKN-geenin mutaatio mutta huono potilailla, joilla on LRRK2-geenin p.R1441G-mutaatio. Kognitiivisten ja neuropsykiatristen oireiden merkittävä eteneminen voi heikentää syväaivostimulaation vastetta potilailla, joilla on LRRK2-geenin p.T2013S-mutaatio tai SNCA- tai GBA-geenien mutaatio

Author response: Effects of orthostatic hypotension on cognition in Parkinson disease

OBJECTIVE: To investigate the relation between orthostatic hypotension (OH) and posture-mediated cognitive impairment in persons with Parkinson's disease (PD) without dementia. METHODS: There were 55 participants: 37 non-demented individuals with idiopathic PD, including 18 with OH (PDOH), and 19 without (PDWOH), and18 control participants (C). All participants completed neuropsychological tests in the supine and in the upright tilted position. Blood pressure was assessed in each posture using a standardized oscillometric cuff at the right brachial artery. RESULTS: The two PD groups performed similarly while supine, with a profile notable for executive dysfunction consisting of deficits in sustained attention, response inhibition, and semantic verbal fluency, as well as reduced verbal memory encoding and retention. When upright, these deficits were exacerbated and broadened to include additional cognitive functions in the PDOH group: deficits in phonemic verbal fluency, psychomotor speed, and both basic and complex aspects of auditory working memory. When group-specific supine scores were used as baseline anchors, both PD groups showed cognitive changes following tilt, though the PDOH group had a wider range of deficits in the executive functioning and memory domains and was the only group to show significant changes in visuospatial skills. CONCLUSIONS: Cognitive deficits in idiopathic PD have been widely reported, though assessments are typically performed in the supine position. While both PD groups had supine deficits that aligned with prior studies and clinical findings, we demonstrated that those with PD and orthostatic hypotension had transient, posture-mediated changes in excess of those found in PD without autonomic failure. These observed changes suggest an acute, reversible effect, and as orthostatic hypotension is a significant comorbid factor in PD, an independent target for clinical intervention. Further understanding of the effects of autonomic failure on cognition in other disorders is desirable, particularly in the context of neuroimaging studies and clinical assessments where data are collected only in the supine or seated positions. Identification of a distinct neuropsychological profile in PD with autonomic failure also has implications for functional activities of daily living and overall quality of life.Accepted manuscrip

Progression of Neuropsychiatric Symptoms over Time in an Incident Parkinson's Disease Cohort (ICICLE-PD).

BACKGROUND: Cross-sectional studies have identified that the prevalence of neuropsychiatric symptoms (NPS) in Parkinson's disease (PD) ranges from 70-89%. However, there are few longitudinal studies determining the impact of NPS on quality of life (QoL) in PD patients and their caregivers. We seek to determine the progression of NPS in early PD. METHODS: Newly diagnosed idiopathic PD cases (n = 212) and age-matched controls (n = 99) were recruited into a longitudinal study. NPS were assessed using the Neuropsychiatric Inventory with Caregiver Distress scale (NPI-D). Further neuropsychological and clinical assessments were completed by participants, with reassessment at 18 and 36 months. Linear mixed-effects modelling determined factors associated with NPI-D and QoL over 36 months. RESULTS: Depression, anxiety, apathy and hallucinations were more frequent in PD than controls at all time points (p < 0.05). Higher motor severity at baseline was associated with worsening NPI-D scores over time (β = 0.1, p < 0.05), but not cognition. A higher NPI total score was associated with poorer QoL at any time point (β = 0.3, p < 0.001), but not changed in QoL scores. CONCLUSION: NPS are significantly associated with poorer QoL, even in early PD. Screening for NPS from diagnosis may allow efficient delivery of better support and treatment to patients and their families

Diagnosis and Treatment of Parkinson's Disease

Parkinson's disease is diagnosed by history and physical examination and there are no laboratory investigations available to aid the diagnosis of Parkinson's disease. Confirmation of diagnosis of Parkinson's disease thus remains a difficulty. This book brings forth an update of most recent developments made in terms of biomarkers and various imaging techniques with potential use for diagnosing Parkinson's disease. A detailed discussion about the differential diagnosis of Parkinson's disease also follows as Parkinson's disease may be difficult to differentiate from other mimicking conditions at times. As Parkinson's disease affects many systems of human body, a multimodality treatment of this condition is necessary to improve the quality of life of patients. This book provides detailed information on the currently available variety of treatments for Parkinson's disease including pharmacotherapy, physical therapy and surgical treatments of Parkinson's disease. Postoperative care of patients of Parkinson's disease has also been discussed in an organized manner in this text. Clinicians dealing with day to day problems caused by Parkinson's disease as well as other healthcare workers can use beneficial treatment outlines provided in this book

Everyday walking with Parkinson's disease: understanding personal challenges and strategies

PURPOSE: This qualitative study was designed to explore the personal experience of everyday walking with Parkinson's disease (PD), the challenges and the strategies employed to compensate for difficulties, to help contextualise the scientific knowledge base. METHODS: Semi-structured interviews were undertaken with a sample of 20 people with idiopathic PD (12 male, 8 female; mean age 65 years (range 50 - 80); mean disease duration 10 years (range 2.5 - 26). Verbatim interview transcripts were analyzed thematically using NUD*IST N6 qualitative data analysis software. RESULTS: Walking was invariably performed as an integral part of a purposeful activity within a specific context, termed walking 'plus', with challenges encountered by people with PD in three main areas: Undertaking tasks; negotiating environments; and making transitions to walking. The two key strategies to compensate for difficulties experienced were monitoring through the use of concentration, and correcting through generating rhythm and size of steps. Carers supported monitoring and correcting. CONCLUSION: People with PD need to constantly assess and drive their walking performance. Attentional resources, which can themselves be compromised in PD, were used to accomplish what is normally a largely automatic activity. Personal accounts support scientific hypotheses. Rehabilitation interventions and measurements in PD need to reflect both the physical and psychosocial context of everyday walking

Biomarkers of Parkinson's disease: recent insights, current challenges, and future prospects

Marina Picillo,1 Marcello Moccia,2 Emanuele Spina,2 Paolo Barone,1 Maria Teresa Pellecchia1 1Department of Medicine and Surgery, Center for Neurodegenerative Diseases (CEMAND), Neuroscience Section, University of Salerno, Salerno, Italy; 2Department of Neuroscience, Reproductive and Odontostomatologic Sciences, Federico II University, Naples, Italy Abstract: A biomarker represents a tool possibly helping physicians in predicting onset, diagnosis, and progression of a disease as well as evaluating the response to disease-modifying treatments. Currently, there is no biomarker fulfilling all such ideal criteria for Parkinson's disease (PD). In this article, we have critically reviewed the literature searching for the most reliable and reproducible clinical, biochemical, and imaging biomarkers for prodromal phase, diagnosis, and progression of PD. Different comprehensive batteries of biomarkers have been proposed as a sensitive approach to predict the onset of PD during the prodromal phase. There is a discussion about the redefinition of the clinical diagnosis of PD, including clinical biomarkers as non-motor symptoms; however, on the other hand, we have also observed that imaging biomarkers support the differential diagnosis from other causes of parkinsonism. Various clinical (eg, freezing of gait or cognitive impairment), biochemical (eg, epidermal growth factor, insulin-like growth factor 1, uric acid, etc), and imaging (eg, functional magnetic resonance imaging, voxel-based morphometry, etc) biomarkers may help envisaging disease progression of PD. To conclude, given the lack of a single biomarker that could track the entire course of the disease, our challenge is to find the best combinations of biomarkers for the different stages of the disease. Keywords: biomarkers, Parkinson's disease, progression, motor, imaging , staging, non moto