Natural history of falls in an incident cohort of Parkinson’s disease: early evolution, risk and protective features

The natural history of falls in early Parkinson’s disease (PD) is poorly understood despite the profound effect of falls on outcome. The primary aim of this study was to describe the natural history of falls, and characterise fallers over 54 months in 99 newly diagnosed people with PD. Seventy-nine (79.7%) participants fell over 54 months and 20 (20.3%) remained falls-naïve. Twenty six (26.2%) reported retrospective falls at baseline. Gait outcomes, disease severity and self-efficacy significantly discriminated across groups. Subjective cognitive complaints emerged as the only significant cognitive predictor. Without exception, outcomes were better for non-fallers compared with fallers at any time point. Between group differences for 54 month fallers and non-fallers were influenced by the inclusion of retrospective fallers and showed a broader range of discriminant characteristics, notably stance time variability and balance self-efficacy. Single fallers (n = 7) were significantly younger than recurrent fallers (n = 58) by almost 15 years (P = 0.013). Baseline performance in early PD discriminates fallers over 54 months, thereby identifying those at risk of falls. Clinical profiles for established and emergent fallers are to some extent distinct. These results reiterate the need for timely interventions to improve postural control and gait

Natural history of falls in an incident cohort of Parkinson’s disease: early evolution, risk and protective features

The natural history of falls in early Parkinson’s disease (PD) is poorly understood despite the profound effect of falls on outcome. The primary aim of this study was to describe the natural history of falls, and characterise fallers over 54 months in 99 newly diagnosed people with PD. Seventy-nine (79.7%) participants fell over 54 months and 20 (20.3%) remained falls-naïve. Twenty six (26.2%) reported retrospective falls at baseline. Gait outcomes, disease severity and self-efficacy significantly discriminated across groups. Subjective cognitive complaints emerged as the only significant cognitive predictor. Without exception, outcomes were better for non-fallers compared with fallers at any time point. Between group differences for 54 month fallers and non-fallers were influenced by the inclusion of retrospective fallers and showed a broader range of discriminant characteristics, notably stance time variability and balance self-efficacy. Single fallers (n = 7) were significantly younger than recurrent fallers (n = 58) by almost 15 years (P = 0.013). Baseline performance in early PD discriminates fallers over 54 months, thereby identifying those at risk of falls. Clinical profiles for established and emergent fallers are to some extent distinct. These results reiterate the need for timely interventions to improve postural control and gait

Poor sleep quality and progression of gait impairment in an incident Parkinson’s disease cohort

Abnormal sleep may associate with cognitive decline in Parkinson's disease (PD). Furthermore, sleep dysfunction may associate with worse motor outcome. We hypothesised that PD patients with poor quality sleep would have greater progression in gait dysfunction, due to structural and functional overlap in networks subserving sleep and gait regulation. 12 PD patients and 12 age-matched controls completed longitudinal follow-up over 36 months. Poor sleep efficiency and greater sleep fragmentation correlated significantly with progression of step-width variability, a gait characteristic mediated by postural control, providing evidence that poor sleep in PD is associated with a more rapid deterioration in gait

Categorising Visual Hallucinations in Early Parkinson's Disease.

BACKGROUND: Visual hallucinations (VHs) are common in Parkinson's disease (PD), with prevalence ranging from 27-50% in cross-sectional cohorts of patients with well-established disease. However, minor hallucinations may occur earlier in the disease process than has been previously reported. OBJECTIVE: We sought to categorise VHs in a cohort of newly diagnosed PD patients and establish their relationship to other clinical features. METHODS: Newly diagnosed PD participants (n = 154) were recruited as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in PD (ICICLE-PD) study. Participants completed the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS III), Montreal Cognitive Assessment (MoCA) and Parkinson's Disease Questionnaire (PDQ-39) to assess motor severity, cognition and quality of life (QoL), respectively. VHs were classified using the North East Visual Hallucinations Inventory. Hierarchical regression was used to build predictive models of motor severity, QoL and cognition. RESULTS: 22% (n = 34) of participants experienced recurrent VHs with minor VHs being most frequently reported (64.7% of hallucinators). Complex VHs were present in 32.4% of hallucinating participants. Linear regression showed VHs predicted poorer PDQ-39 and MoCA scores (β= 0.201, p = 0.006 and β= - 0.167, p = 0.01, respectively) but not motor severity (p > 0.05). CONCLUSIONS: Over a fifth of people with newly diagnosed PD reported recurrent VHs; minor hallucinations were the most common, although a small proportion reported complex VHs. Recurrent VHs were found to be a significant independent predictor of cognitive function and QoL but not motor severity. Our findings highlight the importance of screening for VHs at diagnosis.ICICLE-PD was funded by Parkinson’s UK (J-0802, G-1301, G-1507). The research was supported by the Lockhart Parkinson’s Disease Research Fund, the National Institute for Health Research (NIHR) Newcastle Biomedical Research Unit based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University and a NIHR Biomedical Research Centre award to the University of Cambridge/Addenbrooke’s Hospital

The Role of Movement Analysis in Diagnosing and Monitoring Neurodegenerative Conditions: Insights from Gait and Postural Control

Quantifying gait and postural control adds valuable information that aids in understanding neurological conditions where motor symptoms predominate and cause considerable functional impairment. Disease-specific clinical scales exist; however, they are often susceptible to subjectivity, and can lack sensitivity when identifying subtle gait and postural impairments in prodromal cohorts and longitudinally to document disease progression. Numerous devices are available to objectively quantify a range of measurement outcomes pertaining to gait and postural control; however, efforts are required to standardise and harmonise approaches that are specific to the neurological condition and clinical assessment. Tools are urgently needed that address a number of unmet needs in neurological practice. Namely, these include timely and accurate diagnosis; disease stratification; risk prediction; tracking disease progression; and decision making for intervention optimisation and maximising therapeutic response (such as medication selection, disease staging, and targeted support). Using some recent examples of research across a range of relevant neurological conditions—including Parkinson’s disease, ataxia, and dementia— we will illustrate evidence that supports progress against these unmet clinical needs. We summarise the novel ‘big data’ approaches that utilise data mining and machine learning techniques to improve disease classification and risk prediction, and conclude with recommendations for future direction

Gait Progression Over 6 Years in Parkinson’s Disease: Effects of Age, Medication, and Pathology

Background: Gait disturbance is an early, cardinal feature of Parkinson’s disease (PD) associated with falls and reduced physical activity. Progression of gait impairment in Parkinson’s disease is not well characterized and a better understanding is imperative to mitigate impairment. Subtle gait impairments progress in early disease despite optimal dopaminergic medication. Evaluating gait disturbances over longer periods, accounting for typical aging and dopaminergic medication changes, will enable a better understanding of gait changes and inform targeted therapies for early disease. This study aimed to describe gait progression over the first 6 years of PD by delineating changes associated with aging, medication, and pathology. Methods: One-hundred and nine newly diagnosed PD participants and 130 controls completed at least two gait assessments. Gait was assessed at 18-month intervals for up to 6 years using an instrumented walkway to measure sixteen spatiotemporal gait characteristics. Linear mixed-effects models assessed progression. Results: Ten gait characteristics significantly progressed in PD, with changes in four of these characteristics attributable to disease progression. Age-related changes also contributed to gait progression; changes in another two characteristics reflected both aging and disease progression. Gait impairment progressed irrespective of dopaminergic medication change for all characteristics except step width variability. Conclusions: Discrete gait impairments continue to progress in PD over 6 years, reflecting a combination of, and potential interaction between, disease-specific progression and age-related change. Gait changes were mostly unrelated to dopaminergic medication adjustments, highlighting limitations of current dopaminergic therapy and the need to improve interventions targeting gait decline

Cholinergic system changes in Parkinson's disease: emerging therapeutic approaches

In patients with Parkinson's disease, heterogeneous cholinergic system changes can occur in different brain regions. These changes correlate with a range of clinical features, both motor and non-motor, that are refractory to dopaminergic therapy, and can be conceptualised within a systems-level framework in which nodal deficits can produce circuit dysfunctions. The topographies of cholinergic changes overlap with neural circuitries involved in sleep and cognitive, motor, visuo-auditory perceptual, and autonomic functions. Cholinergic deficits within cognition network hubs predict cognitive deficits better than do total brain cholinergic changes. Postural instability and gait difficulties are associated with cholinergic system changes in thalamic, caudate, limbic, neocortical, and cerebellar nodes. Cholinergic system deficits can involve also peripheral organs. Hypercholinergic activity of mesopontine cholinergic neurons in people with isolated rapid eye movement (REM) sleep behaviour disorder, as well as in the hippocampi of cognitively normal patients with Parkinson's disease, suggests early compensation during the prodromal and early stages of Parkinson's disease. Novel pharmacological and neurostimulation approaches could target the cholinergic system to treat motor and non-motor features of Parkinson's disease

Trajectories of pain over 6 years in early Parkinson’s disease: ICICLE-PD

Introduction Pain is a common non-motor symptom in Parkinson’s disease (PD), affecting up to 85% of patients. The frequency and stability of pain over time has not been extensively studied. There is a paucity of high-quality studies investigating pain management in PD. To develop interventions, an understanding of how pain changes over the disease course is required. Methods One hundred and fifty-four participants with early PD and 99 age-and-sex-matched controls were recruited as part of a longitudinal study (Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in PD, ICICLE-PD). Pain data were collected at 18-month intervals over 72 months in both groups using the Nonmotor Symptom Questionnaire (NMSQ), consisting of a binary yes/no response. Two questions from the Parkinson’s Disease Questionnaire (PDQ-39) were analysed for the PD group only. Results Unexplained pain was common in the PD group and occurred more frequently than in age-matched controls. ‘Aches and pains’ occurred more frequently than ‘cramps and muscle spasms’ at each time point (p < 0.001) except 54 months. Conclusions This study shows that pain is prevalent even in the early stages of PD, yet the frequency and type of pain fluctuates as symptoms progress. People with PD should be asked about their pain at clinical consultations and given support with describing pain given the different ways this can present

Trajectories of pain over 6 years in early Parkinson’s disease: ICICLE-PD

Introduction Pain is a common non-motor symptom in Parkinson’s disease (PD), affecting up to 85% of patients. The frequency and stability of pain over time has not been extensively studied. There is a paucity of high-quality studies investigating pain management in PD. To develop interventions, an understanding of how pain changes over the disease course is required. Methods One hundred and fifty-four participants with early PD and 99 age-and-sex-matched controls were recruited as part of a longitudinal study (Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in PD, ICICLE-PD). Pain data were collected at 18-month intervals over 72 months in both groups using the Nonmotor Symptom Questionnaire (NMSQ), consisting of a binary yes/no response. Two questions from the Parkinson’s Disease Questionnaire (PDQ-39) were analysed for the PD group only. Results Unexplained pain was common in the PD group and occurred more frequently than in age-matched controls. ‘Aches and pains’ occurred more frequently than ‘cramps and muscle spasms’ at each time point (p < 0.001) except 54 months. Conclusions This study shows that pain is prevalent even in the early stages of PD, yet the frequency and type of pain fluctuates as symptoms progress. People with PD should be asked about their pain at clinical consultations and given support with describing pain given the different ways this can present