-
Istradefylline effects on tremor dominance (TD) and postural instability and gait difficulty (PIGD).Clinical Parkinsonism & Related... 2023In patients with Parkinson's Disease (PD), two distinct motor subtypes, tremor dominant (TD) and postural instability and gait difficulty (PIGD), can be differentiated...
BACKGROUND
In patients with Parkinson's Disease (PD), two distinct motor subtypes, tremor dominant (TD) and postural instability and gait difficulty (PIGD), can be differentiated using Unified Parkinson's Disease Rating Scale (UPDRS) sub-scores. This analysis of pooled data from eight pivotal studies examined the effect of treatment with istradefylline, a selective adenosine A receptor antagonist, on these subtypes.
METHODS
In eight randomized, placebo-controlled phase 2b/3 trials, patients on levodopa with carbidopa/benserazide experiencing motor complications received istradefylline (20 or 40 mg/day) or placebo for 12 or 16 weeks. TD subtype was defined by the UPDRS II/III items kinetic and postural tremor in right/left hand and (resting) tremor in the face, lips, chin, hands, or feet; PIGD items were freezing, walking, posture, gait, and postural instability. The ratio of mean scores from TD:PIGD items determined subtype (TD [TD:PIGD ratio ≥ 1.5], PIGD [TD:PIGD ratio ≤ 1.0], mixed-type [ratio 1-1.5]).
RESULTS
In total, 2719 patients were included (PIGD, n = 2165; TD, n = 118; mixed-type, n = 188; not evaluable, n = 248). Among TD subtype patients, the least-squares mean change from baseline versus placebo in UPDRS II/III TD-related total score was significant at 20 mg/day istradefylline (-2.21; 95 % CI, -4.05 to -0.36; p = 0.02). For PIGD subtype patients, there was a significant difference from placebo in UPDRS II/III PIGD-related total score at 40 mg/day istradefylline (-0.25; -0.43 to -0.06; p = 0.01).
CONCLUSIONS
The data from this analysis of UPDRS-based motor subtypes suggest that istradefylline can improve motor disability in PD patients with motor fluctuations regardless of PD subtype. Future research should characterize the effects of istradefylline on tremor.
PubMed: 38021343
DOI: 10.1016/j.prdoa.2023.100224 -
Blood Advances Jul 2023Health-related quality of life (HRQoL) and vulnerability are variably affected in patients with myelodysplastic syndromes (MDS) and other cytopenic states; however, the... (Clinical Trial)
Clinical Trial
Health-related quality of life (HRQoL) and vulnerability are variably affected in patients with myelodysplastic syndromes (MDS) and other cytopenic states; however, the heterogeneity of these diseases has limited our understanding of these domains. The National Heart, Lung, and Blood Institute-sponsored MDS Natural History Study is a prospective cohort enrolling patients undergoing workup for suspected MDS in the setting of cytopenias. Untreated patients undergo bone marrow assessment with central histopathology review for assignment as MDS, MDS/myeloproliferative neoplasm (MPN), idiopathic cytopenia of undetermined significance (ICUS), acute myeloid leukemia (AML) with <30% blasts, or "At-Risk." HRQoL data are collected at enrollment, including the MDS-specific Quality of Life in Myelodysplasia Scale (QUALMS). Vulnerability is assessed with the Vulnerable Elders Survey. Baseline HRQoL scores from 449 patients with MDS, MDS/MPN, AML <30%, ICUS or At-Risk were similar among diagnoses. In MDS, HRQoL was worse for vulnerable participants (eg, mean Patent-Reported Outcomes Management Information Systems [PROMIS] Fatigue of 56.0 vs 49.5; P < .001) and those with worse prognosis (eg, mean Euroqol-5 Dimension-5 Level [EQ-5D-5L] of 73.4, 72.7, and 64.1 for low, intermediate, and high-risk disease; P = .005). Among vulnerable MDS participants, most had difficulty with prolonged physical activity (88%), such as walking a quarter mile (74%). These data suggest that cytopenias leading to MDS evaluation are associated with similar HRQoL, regardless of eventual diagnosis, but with worse HRQoL among the vulnerable. Among those with MDS, lower-risk disease was associated with better HRQoL, but the relationship was lost among the vulnerable, showing for the first time that vulnerability trumps disease risk in affecting HRQoL. This study is registered at www.clinicaltrials.gov as NCT02775383.
Topics: Aged; Humans; Anemia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Prospective Studies; Quality of Life
PubMed: 37146263
DOI: 10.1182/bloodadvances.2022009000 -
Sensors (Basel, Switzerland) Oct 2023Characterizing motor subtypes of Parkinson's disease (PD) is an important aspect of clinical care that is useful for prognosis and medical management. Although all PD...
Characterizing motor subtypes of Parkinson's disease (PD) is an important aspect of clinical care that is useful for prognosis and medical management. Although all PD cases involve the loss of dopaminergic neurons in the brain, individual cases may present with different combinations of motor signs, which may indicate differences in underlying pathology and potential response to treatment. However, the conventional method for distinguishing PD motor subtypes involves resource-intensive physical examination by a movement disorders specialist. Moreover, the standardized rating scales for PD rely on subjective observation, which requires specialized training and unavoidable inter-rater variability. In this work, we propose a system that uses machine learning models to automatically and objectively identify some PD motor subtypes, specifically Tremor-Dominant (TD) and Postural Instability and Gait Difficulty (PIGD), from 3D kinematic data recorded during walking tasks for patients with PD (MDS-UPDRS-III Score, 34.7 ± 10.5, average disease duration 7.5 ± 4.5 years). This study demonstrates a machine learning model utilizing kinematic data that identifies PD motor subtypes with a 79.6% F1 score (N = 55 patients with parkinsonism). This significantly outperformed a comparison model using classification based on gait features (19.8% F1 score). Variants of our model trained to individual patients achieved a 95.4% F1 score. This analysis revealed that both temporal, spectral, and statistical features from lower body movements are helpful in distinguishing motor subtypes. Automatically assessing PD motor subtypes simply from walking may reduce the time and resources required from specialists, thereby improving patient care for PD treatments. Furthermore, this system can provide objective assessments to track the changes in PD motor subtypes over time to implement and modify appropriate treatment plans for individual patients as needed.
Topics: Humans; Parkinson Disease; Tremor; Biomechanical Phenomena; Gait; Brain; Gait Disorders, Neurologic; Postural Balance
PubMed: 37837160
DOI: 10.3390/s23198330 -
European Journal of Ageing May 2024In old age, walking difficulty may reduce opportunities to reach valued activity destinations. Walking modifications, e.g., slower pace or using a walking aid, may...
In old age, walking difficulty may reduce opportunities to reach valued activity destinations. Walking modifications, e.g., slower pace or using a walking aid, may enable individuals to continue going where they wish, and hence postpone the consequences of the onset of walking difficulties. We studied visited activity destinations (type, distance) among older people with varying degrees of walking limitations. Community-dwelling 75-85-year-old people living in Jyväskylä (N = 901) were asked to state whether they had no difficulty walking 2 km, had modified their walking, or had difficulty walking. On a digital map, participants located physical exercise, attractive, and regular destinations they had visited during the past month. Destination counts and median distance to destinations from home were computed. Participants with intact walking reported higher counts of physical exercise (IRR = 1.45, 95% CI [1.31, 1.61]) and attractive destinations (IRR = 1.23, 95% CI [1.10, 1.40]) than those with walking difficulty and also visited these destinations further away from home than the others (b = 0.46, 95% CI [0.20, 0.71]). Those with walking modifications reported higher counts of physical exercise destinations than those with walking difficulty (IRR = 1.23, 95% CI [1.09, 1.40]). Counts of regular destinations and distance traveled were not associated with walking limitations. Walking modifications may help people with walking difficulty reach destinations further away from home, potentially contributing to their sense of autonomy. For those with walking difficulty, a low count of destinations other than regular destinations, e.g., shops or healthcare facilities, may signal their abandonment of recreational activities and a decrease in their life space, potentially leading to reduced well-being.
PubMed: 38775867
DOI: 10.1007/s10433-024-00813-1 -
The Journals of Gerontology. Series A,... Oct 2023The Study of Muscle, Mobility and Aging (SOMMA) aims to understand the biological basis of many facets of human aging, with a focus on mobility decline, by creating a...
BACKGROUND
The Study of Muscle, Mobility and Aging (SOMMA) aims to understand the biological basis of many facets of human aging, with a focus on mobility decline, by creating a unique platform of data, tissues, and images.
METHODS
The multidisciplinary SOMMA team includes 2 clinical centers (University of Pittsburgh and Wake Forest University), a biorepository (Translational Research Institute at Advent Health), and the San Francisco Coordinating Center (California Pacific Medical Center Research Institute). Enrollees were age ≥70 years, able to walk ≥0.6 m/s (4 m); able to complete 400 m walk, free of life-threatening disease, and had no contraindications to magnetic resonance or tissue collection. Participants are followed with 6-month phone contacts and annual in-person exams. At baseline, SOMMA collected biospecimens (muscle and adipose tissue, blood, urine, fecal samples); a variety of questionnaires; physical and cognitive assessments; whole-body imaging (magnetic resonance and computed tomography); accelerometry; and cardiopulmonary exercise testing. Primary outcomes include change in walking speed, change in fitness, and objective mobility disability (able to walk 400 m in 15 minutes and change in 400 m speed). Incident events, including hospitalizations, cancer diagnoses, fractures, and mortality are collected and centrally adjudicated by study physicians.
RESULTS
SOMMA exceeded its goals by enrolling 879 participants, despite being slowed by the COVID-19 pandemic: 59.2% women; mean age 76.3 ± 5.0 years (range 70-94); mean walking speed 1.04 ± 0.20 m/s; 15.8% identify as other than Non-Hispanic White. Over 97% had data for key measurements.
CONCLUSIONS
SOMMA will provide the foundation for discoveries in the biology of human aging and mobility.
Topics: Humans; Female; Aged; Aged, 80 and over; Male; Cohort Studies; Pandemics; Walking; Aging; Muscles; Mobility Limitation
PubMed: 36754371
DOI: 10.1093/gerona/glad052 -
Translational Vision Science &... Nov 2023To investigate gait kinematics during single- and dual-task walking in glaucoma patients compared with healthy controls.
PURPOSE
To investigate gait kinematics during single- and dual-task walking in glaucoma patients compared with healthy controls.
METHODS
Nineteen glaucoma patients (10 females, 9 males) and 30 healthy controls (17 females, 13 males) participated in this cross-sectional study. Spatiotemporal gait parameters (e.g., stride length, velocity, minimum toe clearance [MTC]) were assessed using inertial measurement units (sampling frequency 100 Hz) during single-task walking and dual-task walking at a comfortable velocity. During dual-task walking, participants walked and concurrently performed different cognitive tasks in a random order: (i) reaction time task, (ii) N-Back-task, and (iii) letter fluency task with two difficulty levels, respectively. Repeated measures analyses of covariance (Group × Condition) were conducted to analyze the data.
RESULTS
A significant effect of group was found for the coefficient of variation (CoV) of the MTC, F(1,39) = 4.504, P = 0.040, \({\rm{\eta }}_{\rm{p}}^2\) = 0.104, with higher values in glaucoma patients. Based on the effect sizes, a main effect of group was also found for the MTC, F(1,39) = 2.668, P = 0.110, \({\rm{\eta }}_{\rm{p}}^2\) = 0.064, and the MTCCoV dual-task costs, F(1,38) = 3.225, P = 0.08, \({\rm{\eta }}_{\rm{p}}^2\) = 0.078, which was lower and higher, respectively, in glaucoma patients.
CONCLUSIONS
The present study revealed a significantly higher MTC variability as well as medium effect sizes for a lower MTC and higher MTC dual-task costs in glaucoma patients compared with healthy controls, which might be related to a higher risk of falling owing to tripping.
TRANSLATIONAL RELEVANCE
The minimum toe clearance might mirror disease-related changes in walking performance and might have prognostic value for assessing fall risk in glaucoma patients.
Topics: Female; Male; Humans; Glaucoma, Open-Angle; Cross-Sectional Studies; Gait; Glaucoma
PubMed: 38015169
DOI: 10.1167/tvst.12.11.31 -
European Journal of Sport Science Jul 2023Elevated postprandial glucose (PPG) is an independent risk factor for cardiovascular disease. Post-meal exercise effectively reduces PPG concentrations. However, the...
Elevated postprandial glucose (PPG) is an independent risk factor for cardiovascular disease. Post-meal exercise effectively reduces PPG concentrations. However, the effect of accumulated versus continuous post-meal exercise on PPG control remains unclear. This study aimed to investigate the effects of individualized accumulated or continuous exercise on PPG in young adults with obesity.Twenty young adults with obesity (11 males) completed three 4-h randomized crossover trials with 6-14-day washout periods: (1) sitting (SIT), (2) one 30-min walking bout (CONT), and (3) three 10-min walking bouts separated by 20-min resting (ACCU). Walking was initiated 20 min before individual PPG peak after breakfast, which was predetermined by continuous glucose monitoring. Blood samples were collected at 15-30 min intervals, and the 24-h glucose was monitored via continuous glucose monitoring. The 4-h PPG incremental area under the curve (iAUC) was 12.1%±30.9% and 21.5%±21.5% smaller after CONT (= 0.022) and ACCU (< 0.001), respectively, than after SIT. PPG concentrations were lower during CONT at 30-60 min and during ACCU at 30-105 min after breakfast than during SIT (all < 0.05). The 4-h plasma insulin and C-peptide iAUC, and mean amplitude of glycemic excursions were lower after CONT and ACCU than after SIT (all < 0.05). Both continuous and accumulated exercises reduced PPG, insulin, and C-peptide concentrations and improved glucose fluctuations. Accumulated exercise maintained lower PPG concentrations for a longer time than continuous exercise in young adults with obesity. Clinical trial registration No. ChiCTR 2000035064, URL: http://www.chictr.org.cn/showproj.aspx?proj=56584; (registered July 29, 2020).
Topics: Male; Humans; Young Adult; Blood Glucose; C-Peptide; Blood Glucose Self-Monitoring; Exercise; Walking; Obesity; Cross-Over Studies
PubMed: 36738277
DOI: 10.1080/17461391.2023.2177199 -
Sensors (Basel, Switzerland) Jul 2023Distinguishing pathological gait is challenging in neurology because of the difficulty of capturing total body movement and its analysis. We aimed to obtain a convenient...
Distinguishing pathological gait is challenging in neurology because of the difficulty of capturing total body movement and its analysis. We aimed to obtain a convenient recording with an iPhone and establish an algorithm based on deep learning. From May 2021 to November 2022 at Yamagata University Hospital, Shiga University, and Takahata Town, patients with idiopathic normal pressure hydrocephalus ( = 48), Parkinson's disease ( = 21), and other neuromuscular diseases ( = 45) comprised the pathological gait group ( = 114), and the control group consisted of 160 healthy volunteers. iPhone application TDPT-GT captured the subjects walking in a circular path of about 1 meter in diameter, a markerless motion capture system, with an iPhone camera, which generated the three-axis 30 frames per second (fps) relative coordinates of 27 body points. A light gradient boosting machine (Light GBM) with stratified k-fold cross-validation (k = 5) was applied for gait collection for about 1 min per person. The median ability model tested 200 frames of each person's data for its distinction capability, which resulted in the area under a curve of 0.719. The pathological gait captured by the iPhone could be distinguished by artificial intelligence.
Topics: Humans; Artificial Intelligence; Motion Capture; Gait; Walking; Algorithms; Biomechanical Phenomena; Motion
PubMed: 37448065
DOI: 10.3390/s23136217 -
Canadian Geriatrics Journal : CGJ Dec 2023Functional independence is dictated by the ability to perform basic activities of daily living (ADLs). Although hospitalization is associated with impairments in...
Functional independence is dictated by the ability to perform basic activities of daily living (ADLs). Although hospitalization is associated with impairments in function, we know less about patients' functional trajectory following hospitalization. We examined patients' ability to do basic ADLs across pre-admission, admission, and follow-up (discharge or two-weeks post-admission) and determined which factors predicted changes in ADLs at follow-up. A secondary analysis of a small prospective cohort study of older patients (n=83, 50 females, 81 ± 8 years) from the Emergency Department and a Geriatric Unit were included. ADL scores (dressing, walking, bathing, eating, in and out of bed, and using the toilet) and frailty level (via the Clinical Frailty Scale) were measured. Comparing follow-up to pre-admission, patients reported worse ADL scores for dressing (36% of patients), walking (31%), bathing (34%), eating (25%), in and out of bed (37%), and using the toilet (35%). Most patients (59%) had more difficulty with 1+ ADL at follow-up versus pre-admission, with one-fourth of patients having greater difficulty with 3+ ADLs. Older age and higher frailty level were associated with (all, < .04) worse functional scores for eating, getting in and out of bed, and using the toilet (frailty only) at follow-up versus pre-admission. Here, most inpatients experienced worse difficulty performing multiple basic ADLs after hospital admission, potentially predisposing them for re-hospitalization and functional dependence. Older and frailer patients generally were less likely to recover to pre-admission levels. Hospitalization challenges patients' ability to perform ADLs in the short-term, post-discharge. Strategies to improve patients' functional trajectory are needed.
PubMed: 38045878
DOI: 10.5770/cgj.26.664