This chapter reviews the most common sleep disorders in older adults and their treatment. It begins with a brief review of sleep physiology and then gives an outline on how to take a comprehensive sleep history. There are physiological sleep changes related to ageing, but sleep disorders are not part of normal ageing and are often associated with mental or physical disorders, pain, and neurodegenerative disease. The most common sleep disorders include insomnia, obstructive sleep apnoea, restless legs syndrome, REM sleep behaviour disorder, excessive daytime somnolence, and circadian rhythm disorders. An in-depth clinical history, including if possible, bed-partner’s information, is the key to diagnosis. Patients need to be informed about the physiological sleep changes and the principles of sleep hygiene. Many sleep disorders have effective therapies and patients will benefit from pharmacological and nonpharmacological treatment strategies.
Abstract Background Abnormal GGC expansion within the NOTCH2HLC gene causes neuronal intranuclear inclusion disease (NIID), a rare neurodegenerative disease with variable clinical manifestations, including cognitive dysfunction. In addition to GGC repeats, there are two forms of repeated interruptions, GGA and AGC, within NOTCH2NLC repeats. Previous studies reported fewer GGA and more AGC interruptions in patients with Parkinson Disease; fewer GGA and AGC interruptions in patients with essential tremor, compared to NIID patients. These results suggest that trinucleotide interruptions within the NOTCH2NLC GGC repeats could influence the phenotype of disease, although the mechanism is not known. Methods We looked at the repeat compositions in NOTCH2NLC in NIID patients with and without cognitive impairment (CI). NOTCH2NLC repeats were screened by long‐read sequencing on the Oxford Nanopore platform. Results In 13 NIID patients with NOTCH2NLC repeat expansion, 9 (69%) presented with CI. Patients with CI were older [mean (SD) = 69.7 (5.8) vs 63.3 (7.2)], had later age at onset [63.2 (6.5) vs 59.8 (7.1)] and longer disease duration [6.9 (5.2) vs 3.5 (3.9)] than patients without CI. The NOTCH2NLC repeats range from 89‐138 repeats in patients with CI; 82‐166 repeats in patients without CI. Patients with CI carried more GGC repeats [97.7 (1.7) vs 92.8 (9.0)] and less GGA [0.8 (1.3) vs 2.2 (2.8)] and AGC [0.6 (1.0) vs 3.5 (7.4)] interruptions within NOTCH2NLC , compared to patients without CI. Conclusion Our results suggest that NIID patients with cognitive impairment have a purer GGC repeat in NOTCH2NLC compared to patients without cognitive impairment, supporting previous studies that repeat interruptions may modify clinical manifestation of NIID.
Introduction: Subthalamic nucleus deep brain stimulation (STN-DBS) is a proven treatment modality for Parkinson’s disease (PD), reducing dyskinesia and time spent in the “OFF” state. This study evaluates the long-term outcomes of STN-DBS in PD patients up to 10 years post-surgery in Singapore. Method: We conducted a retrospective review of Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) scores, activities of daily living (ADLs), disease milestones, dopaminergic drug prescriptions, and adverse events in patients before and after STN-DBS surgery. Results: A total of 94 PD patients who underwent bilateral STN-DBS were included. STN-DBS reduced time in the “OFF” state by 36.9% at 1 year (P=0.034) and 40.9% at 5 years (P=0.006). Time with dyskinesia did not significantly change. Levodopa equivalent daily dose was reduced by 35.1% by 5 years (P<0.001). MDS-UPDRS-II and III scores increased from 5 years post-DBS by 40.5% and 35.4%, respectively. Independence in ADLs decreased, though not significantly. The prevalence of frequent falls increased at 5 years. Surgery- and device-related adverse events were uncommon and generally mild. Conclusion: STN-DBS provides sustained relief from motor complications and reduced medication requirements in PD patients in Singapore. This study highlights STN-DBS as an effective treatment option, significantly enhancing the quality of life for those with PD.
The biological underpinnings of the PD clusters remain unknown as the existing PD clusters lacks biomarker characterization. We try to identify clinical subtypes of Parkinson Disease (PD) in an Asian cohort and characterize them by comparing clinical assessments, genetic status and blood biochemical markers. A total of 206 PD patients were included from a multi-centre Asian cohort. Hierarchical clustering was performed to generate PD subtypes. Clinical and biological characterization of the subtypes were performed by comparing clinical assessments, allelic distributions of Asian related PD gene (SNCA, LRRK2, Park16, ITPKB, SV2C) and blood biochemical markers. Hierarchical clustering method identified three clusters: cluster A (severe subtype in motor, non-motor and cognitive domains), cluster B (intermediate subtype with cognitive impairment and mild non-motor symptoms) and cluster C (mild subtype and young age of onset). The three clusters had significantly different allele frequencies in two SNPs (Park16 rs6679073 A allele carriers in cluster A B C: 67%, 74%, 89%, p = 0.015; SV2C rs246814 T allele distribution: 7%, 12%, 25%, p = 0.026). Serum homocysteine (Hcy) and C-reactive protein (CRP) levels were also significantly different among three clusters (Mean levels of Hcy and CRP among cluster A B C were: 19.4 ± 4.2, 18.4 ± 5.7, 15.6 ± 5.6, adjusted p = 0.005; 2.5 ± 5.0, 1.5 ± 2.4, 0.9 ± 2.1, adjusted p < 0.0001, respectively). Of the 3 subtypes identified amongst early PD patients, the severe subtype was associated with significantly lower frequency of Park16 and SV2C alleles and higher levels of Hcy and CRP. These biomarkers may be useful to stratify PD subtypes and identify more severe subtypes.
The alpha-synuclein gene promoter (SNCA-Rep1) is associated with Parkinson's disease (PD), but its relationship with performance across individual cognitive domains in early PD is unknown. This study aims to investigate Rep1 polymorphism and longitudinal change in cognition in early PD. In this longitudinal study, Rep1 allele lengths ("long" and "short") were determined in 204 early PD patients. All participants underwent annual neuropsychological assessments and followed up for 3 years. Linear-mixed model was performed to investigate the association of Rep1 status and longitudinal change in individual cognitive domains. At 3 years, significant decline in executive function was observed in long Rep1 allele carriers vs short allele carriers, controlling for potential confounders. This is the first longitudinal study demonstrating that long Rep1 allele carriers are at higher risk for executive dysfunction in early PD.
Clinicians normally use subjective rating scales to estimate the impairment of patients with Parkinson's disease (PD). More objective and quantitative methods of assessment would greatly aid our understanding of the disease. One promising approach is to measure reaction time: the large amount of data recorded in a short period provides precise, reproducible evaluation of the underlying neural decision processes. Manual evoked reaction times and repetitive tapping speed are often used, but differences of experimental design and analysis tend to obscure their interpretation. Saccadic latency, in many ways a simpler and more standardised task, is also normally affected in PD, but its relation to the kind of movement impairment that affects patients' quality of life is less obvious. OBJESTIVE: The aim of this study was to evaluate these tasks in detail and also see whether their use in combination could provide a better measure than each in isolation.We compared three reaction time tasks: saccadometry, and evoked and spontaneous tapping, using protocols as similar as possible, correlating the measurements within a group of PD patients and of age-matched controls.Surprisingly, manual and saccadic performance is uncorrelated in the normal population; but both are similarly affected by PD. The differences between groups are strengthened when the three measures are combined.Saccadic latency can be regarded as an appropriate surrogate for more general kinds of motor impairment. The combination of saccadic and manual parameters enhances their potential use in quantifying disease status and evaluating treatments.
Background: Various classifications have been proposed to subtype Parkinson's disease (PD) based on their motor phenotypes. However, the stability of these subtypes has not been properly evaluated. Objective: The goal of this study was to understand the distribution of PD motor subtypes, their stability over time, and baseline factors that predicted subtype stability. Methods: Participants ( n = 170) from two prospective cohorts were included: the Early PD Longitudinal Singapore (PALS) study and the National Neuroscience Institute Movement Disorders Database. Early PD patients were classified into tremor-dominant (TD), postural instability and gait difficulty (PIGD), and indeterminate subtypes according to the Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) criteria and clinically evaluated for three consecutive years. Results: At baseline, 60.6% patients were TD, 12.4% patients were indeterminate, and 27.1% patients were PIGD subtypes ( p < 0.05). After 3 years, only 62% of patients in TD and 50% of patients in PIGD subtypes remained stable. The mean levodopa equivalent daily dose (LEDD) was higher in the PIGD subtype (276.92 ± 232.91 mg; p = 0.01). Lower LEDD [ p < 0.05, odds ratio (OR) 0.99, 95% confidence interval (CI): 0.98–0.99] and higher TD/PIGD ratios ( p < 0.05, OR 1.77, 95% CI: 1.29–2.43) were independent predictors of stability of TD subtype with an area under the curve (AUC) of 0.787 (95%CI: 0.669–0.876), sensitivity = 57.8%, and specificity = 89.7%. Conclusion: Only 50–62% of PD motor subtypes as defined by MDS-UPDRS remained stable over 3 years. TD/PIGD ratio and baseline LEDD were independent predictors for TD subtype stability over 3 years.
There is currently insufficient long-term data on costs of treatment in patients with Parkinson's disease (PD), which is chronic and progressive, and associated with substantial healthcare costs. Identifying patterns in healthcare utilization and cost may illuminate further discussion on early intervention.To characterize long-term healthcare utilization and costs of PD in newly diagnosed patients managed by movement disorder specialists.Using a longitudinal matched-cohort study of linked data from the National Neuroscience Institute Parkinson's disease and Movement Disorder and healthcare administrative databases in Singapore from 2008-2017, we compared healthcare utilization and costs between patients and controls matched on age, sex, race, and Charlson Comorbidity Index score.1,162 patients met study inclusion criteria and 1,157 matched controls were identified. The total mean annual healthcare cost (at 2017 costs) was significantly increased in patients compared to controls from years 1-9 post-diagnosis. The increased cost was observed 2 years before diagnosis (USD2322 vs. 2052; p < 0.001). Mean annual cost attributable to PD increased from USD1854 at 1-year post-diagnosis to USD2652 at 9 years. Over 9 years, average costs were significantly higher across all domains of healthcare utilization except primary care-cost of intermediate and long-term care was increased by a factor of 2.5, specialist care by 2.3, emergency department visits by 1.6, and hospital admissions by 1.3.PD results in higher healthcare utilization and costs. Pre-diagnosis increase in healthcare utilization observed in patients supports the presence of prodromal PD symptoms and may present an opportunity for early diagnosis.
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