scholarly journals Clinical progression of progressive supranuclear palsy: impact of trials bias and phenotype variants

2021 ◽  
Author(s):  
Duncan Street ◽  
Maura Malpetti ◽  
Timothy Rittman ◽  
Boyd C P Ghosh ◽  
Alexander G Murley ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Progressive Supranuclear Palsy ◽  
Trial Design ◽  
Mini Mental State Examination ◽  
Rating Scale ◽  
Clinical Progression ◽  
Eligibility Criteria ◽  
Richardson’S Syndrome ◽  
State Examination ◽  
Addenbrooke’S Cognitive Examination

Abstract Progressive supranuclear palsy causes diverse clinical presentations, including classical Richardson’s syndrome and several variant phenotypes. Clinical trials of disease-modifying therapies have recently been completed, with more planned for the next two years. However, many people with progressive supranuclear palsy do not meet eligibility criteria for these clinical trials. Understanding clinical progression with different phenotypes would improve trial design and enhance the accuracy of risk-benefit and cost-benefit assessments of new treatments for progressive supranuclear palsy. We set out to determine rates of motor and cognitive progression of possible, probable and definite progressive supranuclear palsy, with different phenotypes, from a representative cohort in a regional United Kingdom healthcare service. Longitudinal clinical data from people with Richardson’s syndrome and variant phenotypes were analysed using linear mixed-modelling, using both the full and modified versions of the Progressive Supranuclear Palsy Rating Scale, Mini-Mental State Examination, and the revised Addenbrooke’s Cognitive Examination. Subgroup analyses considered patients meeting recent phase II trial entry criteria and patients with neuropathological confirmation. 227 patients (male = 59%, mean age [±Standard Deviation], 71.8[±7.0] years) were followed for a mean 21.6[±15.6] months. One hundred and seventy-four (77%) had Richardson’s syndrome at the outset, twenty-five had cortical variant presentations (13%, frontal, corticobasal, speech and language variants) and twenty-eight had subcortical variant presentations (14%, parkinsonism, postural instability and gait freezing variants). Across all participants, annual progression in Richardson’s syndrome was faster than variant phenotypes on the Mini-Mental State Examination (-1.8 vs -0.9/year, p = 0.005) and revised Addenbrooke’s Cognitive Examination (-5.3 vs -3.0/year, p = 0.01) but not the Progressive Supranuclear Palsy Rating Scale (9.0 vs 7.1/year, p = 0.2) nor the modified Progressive Supranuclear Palsy Rating Scale (2.7 vs 2.3/year, p = 0.4). However, for those with more than one years’ follow-up, a significant difference was observed between Richardson’s syndrome and variant phenotypes in Progressive Supranuclear Palsy Rating Scale (8.7 vs 6.3/year, p = 0.04). Survival was longer in variant phenotypes than Richardson’s syndrome (7.3[±3.9] vs 5.6[±2.0] years, p = 0.02). Pathologically confirmed cases (n = 49) supported these findings. Patients meeting basic trial-eligibility criteria (n = 129) progressed faster on the Progressive Supranuclear Palsy Rating Scale than trial-not-eligible patients (10.1 vs 6.1/year, p = 0.001). In conclusion, phenotypes other than Richardson’s syndrome show slower progression and longer survival. Trial criteria do not select representative progressive supranuclear palsy cases. This has implications for trial design, and application of trial results to clinically more diverse patient populations.

scholarly journals Understanding Fatigue in Progressive Supranuclear Palsy: Prevalence and Associated Factors

2021 ◽  
Author(s):  
Jong Hyeon Ahn ◽  
Joomee Song ◽  
Dong Yeong Lee ◽  
Jinyoung Youn ◽  
Jin Whan Cho
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Associated Factors ◽  
Mini Mental State Examination ◽  
Disease Duration ◽  
Rating Scale ◽  
Motor Symptom ◽  
Summary Index ◽  
State Examination ◽  
Insight Into

Abstract Background: Fatigue is a common and disabling non-motor symptom (NMS) of Parkinson’s disease (PD); however, it has been poorly understood in patients with progressive supranuclear palsy (PSP). We investigated the association between fatigue, clinical features, and other NMS in patients with probable PSP.Methods: In 72 probable PSP patients, fatigue was investigated using the PD fatigue scale (PFS). Further, all patients were evaluated using the PSP rating scale (PSPRS), Beck Depression Inventory (BDI), Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), PD Sleep Scale (PDSS), NMS scale (NMSS), PD Questionnaire-39 summary index (PDQ-39 SI), and Scale for Outcomes in PD-Autonomic (SCOPA-AUT). Results: The prevalence of fatigue was 38.9% (28/72) in patients with PSP. Logistic regression analysis showed that depression (BDI) was the factor associated with fatigue. We divided the patients into primary (fatigue without depression, n =16), secondary (fatigue with depression, n = 12), and non-fatigue groups. There were no differences in age, sex, disease duration, and PSPRS, PDSS, MMSE, and FAB scores among the three groups. The primary fatigue group had higher scores in PDQ-39 SI compared to the non-fatigue group. The secondary fatigue group showed higher scores in NMSS, PDQ-39 SI, and SCOPA-AUT compared to the non-fatigue group. PFS was positively correlated with NMSS and PDQ-39 SI and SCOPA-AUT.Conclusions: Fatigue is common in patients with PSP and is associated with the NMS and the quality of life in these patients. The present study provides meaningful insight into fatigue in patients with PSP.

scholarly journals Understanding fatigue in progressive supranuclear palsy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jong Hyeon Ahn ◽  
Joomee Song ◽  
Dong Yeong Lee ◽  
Jinyoung Youn ◽  
Jin Whan Cho
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Sleep Disturbances ◽  
Mini Mental State Examination ◽  
Disease Duration ◽  
Rating Scale ◽  
Motor Symptom ◽  
Summary Index ◽  
State Examination ◽  
Insight Into

AbstractFatigue is a common and disabling non-motor symptom (NMS) of Parkinson’s disease (PD); however, it has been poorly understood in patients with progressive supranuclear palsy (PSP). We investigated the association between fatigue, clinical features, and other NMS in patients with probable PSP. In 72 probable PSP patients, fatigue was investigated using the Parkinson Fatigue Scale (PFS). Further, all patients were evaluated using the PSP rating scale (PSPRS), Beck Depression Inventory (BDI), Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), PD Sleep Scale (PDSS), NMS scale (NMSS), PD Questionnaire-39 summary index (PDQ-39 SI), and Scale for outcomes in PD-Autonomic (SCOPA-AUT). The prevalence of fatigue assessed by PFS was 38.9% (28/72) in patients with PSP. The secondary fatigue was defined as fatigued patients with depression and/or sleep disturbances. We divided the patients into primary (n = 15), secondary (n = 13), and non-fatigue groups. There were no differences in age, sex, disease duration, and PSPRS, PDSS, MMSE, and FAB scores among the three groups. The primary fatigue group had higher scores in PDQ-39 SI compared to the non-fatigue group. The secondary fatigue group showed higher scores in NMSS, PDQ-39 SI, and SCOPA-AUT compared to the non-fatigue group. PFS was positively correlated with NMSS and PDQ-39 SI and SCOPA-AUT. Fatigue is common in patients with PSP and is associated with the NMS and the quality of life in these patients. The present study provides meaningful insight into fatigue in patients with PSP.

scholarly journals Neurokognitív zavarok diagnosztizálási és kezelési lehetőségei Parkinson-kórban

2015 ◽  
Vol 156 (23) ◽  
pp. 915-926 ◽  
Author(s):  
Tivadar Lucza ◽  
Kázmér Karádi ◽  
Sámuel Komoly ◽  
József Janszky ◽  
János Kállai ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Assessment ◽  
Mini Mental State Examination ◽  
Rating Scale ◽  
Neurocognitive Disorders ◽  
Dsm 5 ◽  
Mattis Dementia Rating Scale ◽  
State Examination ◽  
Addenbrooke’S Cognitive Examination

In the present review the recent developments in the definitions of neurocognitive disorders associated with Parkinson’s disease are summarized including the possibilities for screening and treating. For a long time, the recognition of neurocognitive disorders associated in patients with Parkinson’s disease was unsatisfactory due to the heterogeneity of definitions. The recently developed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) introduced the definitions of mild and major neurocognitive disorders instead of mild cognitive impairment and dementia. The new DSM-5 definitions are clinically well applicable; therefore, the validation of the most frequent screening tests (Mini-Mental State Examination; Addenbrooke’s Cognitive Examination; Montreal Cognitive Assessment; Mattis Dementia Rating Scale) is warranted. Based on a Hungarian sample of 295 patients with Parkinson’s disease, the cut-off scores having the best discriminative values are highly dependent on education years (Addenbrooke’s Cognitive Examination: 0–8 years of education: 82.5 points, 9–12 years of education: 83.5 points, and ≥13 years of education: 84.5 points; Mini-Mental State Examination: 26.5–27.5–28.5 points, Montreal Cognitive Assessment: 23.5–24.5–24.5 points, Mattis Dementia Rating Scale: 138.5–139.5–139.5 points, respectively). Orv. Hetil., 2015, 156(23), 915–926.

scholarly journals Validation of the new pathology staging system for progressive supranuclear palsy

2021 ◽  
Author(s):  
Mayen Briggs ◽  
Kieren SJ Allinson ◽  
Maura Malpetti ◽  
Maria Grazia Spillantini ◽  
James Benedict Rowe ◽  
...  
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Staging System ◽  
Clinical Severity ◽  
Potential Association ◽  
Cortical Regions ◽  
Operational Criteria ◽  
Richardson’S Syndrome ◽  
Addenbrooke’S Cognitive Examination

AbstractProgressive supranuclear palsy (PSP) is a neurodegenerative disorder associated with neuroglial accumulation of 4-repeat tau protein. Kovacs et al. have recently proposed a new semi-quantitative staging system to categorise the severity of PSP pathology, using the distribution of tau aggregates as it progresses from subcortical to cerebellar and cortical regions. Here, we test the new PSP pathology staging system in an independent series of PSP, and test the potential association between pathology stage and clinical severity at death. We include tissue from 35 people with a clinical diagnosis of PSP (including N=25 with Richardson’s syndrome and N=10 with other phenotypes). Donors had attended longitudinal clinical studies at the Cambridge Centre Parkinson-plus including assessment of clinical severity by the PSP rating scale (PSPRS) and cognitive performance by the revised Addenbrooke’s Cognitive Examination (ACE-R). We rated tau pathology from none-to-severe in six regions. We focused on (I) astrocytic tau inclusions in striatum, frontal and occipital regions, and (II) neuronal and oligodendroglia tau inclusions in globus pallidus, subthalamic nucleus, and cerebellum. Thirty-two cases (91%) readily conformed to the new staging system, ranging from stage 2 to 6. Staging system applied to brains from people with different clinical phenotypes of PSP. Neuropathology stages correlated with clinical severity at death using both PSPRS and ACE-R, weighted for the interval between last assessment and donation. Our study supports the proposed sequential distribution of tau aggregates in PSP pathology, and the hypothesised relationship between clinical and neuropathological severity. For future studies, in order to standardise rating between centres, we propose a set of operational criteria for region-specific thresholds or tau burden, and a visual guide.

Validity of the Elderly Behavior Assessment for Relatives (EBAR)

2000 ◽  
Vol 16 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Lina Pezzuti ◽  
Caterina Laicardi ◽  
Marco Lauriola
Keyword(s):  
Cognitive Functioning ◽  
Mini Mental State Examination ◽  
Rating Scale ◽  
Good Health ◽  
The Elderly ◽  
Behavior Assessment ◽  
Elderly Persons ◽  
Behavior Rating Scale ◽  
Components Analysis ◽  
State Examination

Summary: An Elderly Behavior Assessment for Relatives (EBAR), updating the GERRI ( Schwartz, 1983 ), was administered to relatives (or significant others) of 349 elderly persons, from 60 to over 80 years of age, living at home, in good health and without cognitive impairment. A trained psychologist administered subjects the Life Satisfaction for Elderly Scale (LSES), the Instrumental Activity of Daily Living (IADL), the Mini Mental State Examination (MMSE), and personally answered to an overall elderly behavior rating scale (RA). EBAR items were first examined. The more attractive and less discriminative statements were excluded. A principal components analysis was carried out on the remaining EBAR items. Three factors were extracted. After varimax rotation they were tentatively labeled: Everyday Cognitive Functioning, Depression, and Hostility. Factor-driven EBAR subscales were designed, taking into account simpler items in the factor matrix. Results provide evidence for EBAR construct validity. Everyday Cognitive Functioning is connected to the IADL and the RA scores; Depression is very highly related to the LSES; Hostility is weakly related to RA, IADL, and MMSE, indicating that the scale needs further investigation.

Association of Progressive Supranuclear Palsy Rating Scale with Progressive Supranuclear Palsy Quality of Life Scale

2021 ◽  
pp. 1-8
Author(s):  
Alexander Pantelyat ◽  
Lenora Higginbotham ◽  
Liana Rosenthal ◽  
Diane Lanham ◽  
Vanessa Nesspor ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trials ◽  
Progressive Supranuclear Palsy ◽  
Rating Scale ◽  
Linear Regression Analysis ◽  
Disease Evolution ◽  
Quality Of Life Scale ◽  
Patient Reported ◽  
Scale Scores

<b><i>Introduction:</i></b> There is growing interest in using patient-reported outcomes as end points in clinical trials, such as the progressive supranuclear palsy quality of life (PSP-QoL) scale. However, this tool has not been widely validated and its correlation with validated motor scales has not been explored. To evaluate the potential utility of using PSP-QoL as an outcome, it is important to examine its relationship with a standard scale used to evaluate neurologic parameters, such as the PSP Rating Scale. <b><i>Methods:</i></b> PSP-QoL and PSP Rating Scale scores were gathered from 60 clinically diagnosed PSP patients, including patients with Richardson syndrome PSP (PSP-RS, <i>n</i> = 43) and those with non-RS PSP variants (<i>n</i> = 17). Linear regression analysis adjusted for age, sex, and disease duration was used to evaluate the cross-sectional relationship between the total and subscale scores of the 2 instruments. <b><i>Results:</i></b> Among 60 PSP patients, there was a significant correlation between total PSP-QoL and PSP Rating Scale scores. The physical and mentation subscales of each instrument also demonstrated significant correlations. Comparisons among PSP subtypes indicated that worsening PSP-QoL Total and Physical subscale scores correlated with worsening PSP Rating Scale gait subscale scores more strongly for the non-RS PSP variants than for PSP-RS. <b><i>Discussion:</i></b> There is a significant association between the total scores and many of the subscale scores of the PSP-QoL and the PSP Rating Scale. Additionally, the relationship between these measures may differ for PSP-RS and non-RS variants. These findings suggest that the PSP-QoL may be useful in clinical trials as a patient-reported outcome measure. Large prospective multicenter studies utilizing the PSP-QoL are necessary to examine its relationship to disease evolution and changes in the PSP Rating Scale.

The agreement of the Mattis Dementia Rating Scale with the Mini-Mental State Examination

2002 ◽  
Vol 17 (7) ◽  
pp. 685-686 ◽  
Author(s):  
W. Freidl ◽  
W.-J. Stronegger ◽  
A. Berghold ◽  
B. Reinhart ◽  
K. Petrovic ◽  
...  
Keyword(s):  
Mental State ◽  
Mini Mental State Examination ◽  
Rating Scale ◽  
Mattis Dementia Rating Scale ◽  
Dementia Rating Scale ◽  
State Examination

Effect of aerobic exercise on post-stroke cognitive function: a systematic review

2020 ◽  
Vol 27 (9) ◽  
pp. 1-15
Author(s):  
Muhammad Aliyu Abba ◽  
Olubukola Adebisi Olaleye ◽  
Talhatu Kolapo Hamzat
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Cognitive Function ◽  
Aerobic Exercise ◽  
Mini Mental State Examination ◽  
Cognitive Impairments ◽  
Inclusion Criteria ◽  
Post Stroke ◽  
Online Databases ◽  
State Examination

Background/Aims Literature suggests that aerobic exercise improves cognitive impairments post stroke. This systematic review was conducted to analyse evidence on the effectiveness of aerobic exercise in improving post-stroke cognitive impairments. Methods Online databases (PubMed, EMBASE and Web of Science) were systematically searched from inception until 13 July 2017 using the keywords stroke/exercise/cognition. Clinical trials that met the inclusion criteria were assessed for methodological quality using the PEDro scale. Extracted data were synthesised for evidence. Results A total of seven studies met the inclusion criteria. Participants in most of the studies were aged over 60 years and the majority had ischaemic stroke. The most commonly used measure for assessing cognition was the Mini Mental State Examination. The majority of studies included moderate to high intensity exercise (50–70% of VO2max) for 30–60 minutes three to five times per week. There is moderate evidence that aerobic exercise enhances global cognitive function, attention and working memory. Evidence that aerobic exercise improves memory, levels of brain-derived neurotrophic factor and executive function is conflicting and limited. Conclusions Aerobic exercise is moderately effective in improving post-stroke cognitive impairments. More clinical trials are needed in view of the methodological limitations and paucity of existing studies.

scholarly journals Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder

Brain ◽  
2020 ◽  
Author(s):  
Dario Arnaldi ◽  
Andrea Chincarini ◽  
Michele T Hu ◽  
Karel Sonka ◽  
Bradley Boeve ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Mental State ◽  
Rem Sleep ◽  
Mini Mental State Examination ◽  
Rating Scale ◽  
Bayesian Classifier ◽  
Examination Score ◽  
Sleep Behaviour ◽  
State Examination

Abstract This is an international multicentre study aimed at evaluating the combined value of dopaminergic neuroimaging and clinical features in predicting future phenoconversion of idiopathic REM sleep behaviour (iRBD) subjects to overt synucleinopathy. Nine centres sent 123I-FP-CIT-SPECT data of 344 iRBD patients and 256 controls for centralized analysis. 123I-FP-CIT-SPECT images were semiquantified using DaTQUANTTM, obtaining putamen and caudate specific to non-displaceable binding ratios (SBRs). The following clinical variables were also analysed: (i) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, motor section score; (ii) Mini-Mental State Examination score; (iii) constipation; and (iv) hyposmia. Kaplan-Meier survival analysis was performed to estimate conversion risk. Hazard ratios for each variable were calculated with Cox regression. A generalized logistic regression model was applied to identify the best combination of risk factors. Bayesian classifier was used to identify the baseline features predicting phenoconversion to parkinsonism or dementia. After quality check of the data, 263 iRBD patients (67.6 ± 7.3 years, 229 males) and 243 control subjects (67.2 ± 10.1 years, 110 males) were analysed. Fifty-two (20%) patients developed a synucleinopathy after average follow-up of 2 years. The best combination of risk factors was putamen dopaminergic dysfunction of the most affected hemisphere on imaging, defined as the lower value between either putamina (P &lt; 0.000001), constipation, (P &lt; 0.000001) and age over 70 years (P = 0.0002). Combined features obtained from the generalized logistic regression achieved a hazard ratio of 5.71 (95% confidence interval 2.85–11.43). Bayesian classifier suggested that patients with higher Mini-Mental State Examination score and lower caudate SBR asymmetry were more likely to develop parkinsonism, while patients with the opposite pattern were more likely to develop dementia. This study shows that iRBD patients older than 70 with constipation and reduced nigro-putaminal dopaminergic function are at high risk of short-term phenoconversion to an overt synucleinopathy, providing an effective stratification approach for future neuroprotective trials. Moreover, we provide cut-off values for the significant predictors of phenoconversion to be used in single subjects.

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