Progressive supranuclear palsy's economical burden: the use and costs of healthcare resources in a large health provider in Israel.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative movement disorder with no disease modifying therapy currently available. Data on the costs associated with PSP are scarce. This study aims to assess the direct medical expenditure of patients with PSP (PwPSP) throughout disease course. METHODS: This retrospective cohort study is based on the data of a large state-mandated health provider in Israel. We identified PwPSP who were initially diagnosed between 2000 and 2017. Each PwPSP was randomly matched to three health-plan members without PSP by birth-year, sex, and socioeconomic status. Healthcare resources' utilization and related costs were assessed. RESULTS: We identified 88 eligible PwPSP and 264 people in the reference group; mean age at diagnosis was 72.6 years (SD = 8.4) and 53.4% were female. The annual direct costs of PwPSP have risen over time, reaching US$ 21,637 in the fifth year and US$ 36,693 in the tenth year of follow-up vs US$ 8910 in the year prior diagnosis. Compared to people without PSP, PwPSP had substantially higher medical expenditure during the years prior- and post-index date. CONCLUSION: The present study demonstrates higher economic burden, which increases with time, in PwPSP as compared to those without.

Energy expenditure, body composition and dietary habits in progressive supranuclear palsy.

INTRODUCTION: Little is known about metabolic changes in progressive supranuclear palsy. Goals of the present study are to: (1) investigate whether early progressive supranuclear palsy is associated with changes in energy expenditure, body composition and dietary intake compared with Parkinson's disease and healthy controls; (2) assess the accuracy of the Harris-Benedict equation to predict measured rest energy expenditure in progressive supranuclear palsy; (3) verify differences according to sex, phenotypes, disease severity and presence of dysphagia in progressive supranuclear palsy. METHODS: Twenty-one progressive supranuclear palsy, 41 Parkinson's disease and nine healthy controls were included. Rest energy expenditure was assessed with indirect calorimeter, body composition with bio-impedance analysis and physical activity and dietary intake were estimated with a validated frequency questionnaire. Parametric testing was used to analyze differences between groups. RESULTS: Progressive supranuclear palsy showed reduced total daily energy expenditure and physical activity compared to both other cohorts (p < 0.001) and a tendency toward lower fat-free mass compared to Parkinson's disease (p > 0.05). Limited accuracy was shown for the Harris-Benedict equation (accurate prediction frequency < 60%). Greater disease severity was associated with lower rest energy expenditure (p = 0.030), fat-free mass (p = 0.026) and muscle mass (p = 0.029). CONCLUSION: Greater disease severity is associated with reduction in rest energy expenditure likely due to the reduction in lean mass and muscle mass. Such data may pave the way to clinical trials evaluating the efficacy of muscle-targeted nutritional support and physical therapy in preserving muscle mass and improving motor performances in progressive supranuclear palsy at early stages.

Laboratory based assessment of gait and balance impairment in patients with progressive supranuclear palsy.

BACKGROUND: Gait and balance abnormalities are a significant source of morbidity and mortality in progressive supranuclear palsy (PSP). Gait impairment in PSP is primarily assessed clinically on exam or with the use of rating scales. Three dimensional video based gait and balance analysis performed in a laboratory setting is a highly accurate method of motion analysis (Wren et al., 2020), however limited data is available in patients with PSP. RESEARCH QUESTION: In this study we assess the objective features of postural control, kinematics, kinetic and temporal-spatial gait metrics in PSP, using three-dimensional video motion analysis in a laboratory setting compared to normal controls. METHODS: Three-dimensional motion was captured using a 10-camera motion capture system, 41 body markers and ground embedded force plates in 16 patients with PSP patients and compared to motorically normal controls. RESULTS: Spatiotemporal, kinematic, and kinetic gait measures effectively differentiated patients with PSP from controls. Patients had slower gait velocity, lower cadence, increased double support time and abnormal antero-posterior sway. Joint kinematics and kinetics were reduced and showed less variation among patients with PSP compared to controls which is suggestive of bradykinesia. Objective gait measures of abnormality correlated with clinical disease severity. Postural sway metrics distinguished PSP from controls and captured gait imbalance. SIGNIFICANCE: Objective measures of gait and balance abnormalities in patients with PSP provide an outcome measure that can be potentially used for early disease detection, in clinical trials and to validate portable motion capture devices in the future.

Cognitive decline on the Repeatable Battery for the Assessment of Neuropsychological Status in progressive supranuclear palsy.

Objective: Progressive supranuclear palsy (PSP) is associated with a variety of cognitive deficits, but few studies have reported on its cognitive trajectory across time, especially on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).Methods: Two hundred twenty participants diagnosed with Richardson's syndrome of PSP (PSP-RS) were evaluated with the RBANS at baseline, six months, and one year with alternate forms.Results: When using dependent t-tests, significant declines were observed on all Indexes of the RBANS from baseline to six months (ps < 0.01). Between six months and one year, significant declines were observed on three Indexes of the RBANS (ps < 0.05). Using existing regression-based change formulae from cognitively intact older adults, these participants with PSP showed significant decline on all RBANS Indexes (ps < 0.01) across one year. Finally, new regression-based change formulae were developed on this sample of individuals with PSP-RS to more precisely evaluate cognitive change in this condition.Conclusion: In this large, longitudinal cohort of participants with PSP-RS, many (but not all) showed notable cognitive decline across six months and one year on the RBANS. The different methods of examining change across time yielded different results, with regression-based methods appearing to more accurately capture decline in this sample. These findings are expected to allow clinicians to more accurately evaluate cognitive trajectories in patients with PSP, as well as make better estimates of prognosis and offer more appropriate treatment recommendations. Such findings are also expected to inform clinical trials as to the changes in cognitive outcomes with this neurological condition.

Cognitive deficits in progressive supranuclear palsy on the Repeatable Battery for the Assessment of Neuropsychological Status.

Progressive supranuclear palsy (PSP) is associated with a variety of cognitive deficits, as well as motor and psychiatric disturbances. As clinical trials for PSP evolve, briefer screening instruments will be needed to determine cognitive effects of interventions. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) may fill this gap. Three hundred four participants diagnosed with Richardson's syndrome of PSP were evaluated with the RBANS, as well as other scales typically used in PSP. RBANS performances for these participants fell significantly below expectations for the Total Scale score and all five Indexes. Cognitive scores on the RBANS were also significantly related to other markers of PSP (e.g., motor and functional abilities, depression, global cognition). Compared to other clinical conditions from the literature, patients with PSP show impairment on tests of visuospatial perception and construction and attention. Although additional research is needed, the current study supports the clinical applicability of the RBANS in patients with PSP, as well as its potential for future clinical trials.

Pittsburgh Compound B and AV-1451 positron emission tomography assessment of molecular pathologies of Alzheimer's disease in progressive supranuclear palsy.

INTRODUCTION: Little is known about Alzheimer's disease molecular proteins, beta-amyloid and paired helical filament (PHF) tau, in progressive supranuclear palsy (PSP). Recent techniques have been developed to allow for investigations of these proteins in PSP. We determined the frequency of beta-amyloid deposition in PSP, and whether beta-amyloid deposition in PSP is associated with PHF-tau deposition pattern, or clinical features. METHODS: Thirty probable PSP participants underwent MRI, [18F]AV-1451 PET and Pittsburgh compound B (PiB) PET. Apolipoprotein (APOE) genotyping was also performed. A global PiB standard-uptake value ratio (SUVR) was calculated. AV-1451 SUVRs were calculated for a set of Alzheimer's disease (AD)-related regions and a set of PSP-related regions. Voxel-level analyses were conducted to assess for differences in AV-1451 uptake patterns and MRI atrophy between PiB(+) and PiB(-) cases compared to 60 normal PiB(-) controls. Statistical testing for correlations and associations between variables of interest were also performed. RESULTS: Twelve subjects (40%) showed beta-amyloid deposition. Higher PiB SUVR correlated with older age but not with AV-1451 SUVR in the AD- or PSP-related regions. Higher AV-1451 SUVR in AD-related regions was associated with higher AV-1451 SUVR in PSP-related regions. We found little evidence for beta-amyloid related differences in clinical metrics, proportion of APOE e4 carriers, pattern of AV-1451 uptake, or pattern of atrophy. CONCLUSION: Beta-amyloid deposition occurs in a relatively high proportion of PSP subjects. Unlike in Alzheimer's disease, however, there is little evidence that beta-amyloid, and PHF-tau, play a significant role in neurodegeneration in PSP.

Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) performance in progressive supranuclear palsy and multiple system atrophy.

To determine if Montreal Cognitive Assessment (MoCA) is more sensitive than the commonly used Mini-Mental State Examination (MMSE) in detecting cognitive abnormalities in patients with probable progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) compared with Parkinson's disease (PD). In this multicenter observational study, MMSE and MoCA were administered in a random order to 130 patients: 35 MSA, 30 PSP and 65 age, and education and gender matched-PD. We assessed between-group differences for MMSE, MoCA, and their subitems. Receiver-operating characteristic (ROC) curves were calculated. The mean MMSE was higher than the mean MoCA score in each MSA (27.7 ± 2.4 vs. 22.9 ± 3.0, p < 0.0001), PSP (26.0 ± 2.9 vs. 18.2 ± 3.9, p < 0.0001), and PD (27.3 ± 2.0 vs. 22.3 ± 3.5, p < 0.0001). MoCA total score as well as its letter fluency subitem differentiated PSP from MSA and PD with high specificity and moderate sensitivity. More specifically, a cut-off score of 7 F-words or less per minute would support a diagnosis of PSP (PSP vs. PD: 86 % specificity, 70 % sensitivity; PSP vs. MSA: 71 % specificity, 70 % sensitivity). By contrast, MMSE presented an overall ceiling effect for most subitems, except for the pentagon scores, where PSP did less well than MSA or PD patients. These preliminary results suggest that PSP and MSA, similar to PD patients, may present normal MMSE and reduced MoCA performance. Overall, MoCA is more sensitive than MMSE in detecting cognitive impairment in atypical parkinsonism and together with verbal fluency would be a useful test to support PSP diagnosis.

Utility of Frontal Assessment Battery in detection of neuropsychological dysfunction in Richardson variant of progressive supranuclear palsy.

Progressive supranuclear palsy is characterized by motor, cognitive and behavioral features. In Richardson's syndrome of PSP (PSP-RS) executive dysfunction is quite prominent. Frontal Assessment Battery (FAB) is one of the most popular screening tests in the differential diagnosis of bradykinetic rigid syndromes. The study aimed at analyzing FAB subscores in relation to neuropsychological assessment results. Twenty patients with PSP-RS (12 with probable and eight with possible diagnosis) participated in the study. Sixteen PSP-RS patients scored below 15 on FAB. Among four patients having scored above cut-off (12 points) on FAB, two demonstrated both executive and language deficits, while the other two presented with only selective executive deficits on comprehensive neuropsychological evaluation. FAB is a useful screening measure in PSP, but it may not detect subtle executive deficits. Moreover, language performance seems to contribute significantly to FAB scores. Thus, FAB should be treated as "frontal" rather than "executive" screening task, in line with its name.

Characteristics and symptom management of progressive supranuclear palsy: a multidisciplinary approach.

Progressive supranuclear palsy (PSP), a neurodegenerative disorder that may be mistaken for Parkinson's disease early in its course, is the most common type of atypical parkinsonism. PSP is fatal; it transforms a normal person into an invalid within 5-7 years of the onset of symptoms. PSP requires a multidisciplinary approach to symptom management and treatment. The neuroscience nurse who is knowledgeable about PSP and the complex way in which it overlaps with numerous other devastating neurological diagnoses can help in achieving the correct diagnosis and treatment. The nurse must understand the disease pathophysiology and the plan of care required and is instrumental in recognizing the needs of the patient and the family.

Can the frontal assessment battery (FAB) differentiate bradykinetic rigid syndromes? Relation of the FAB to formal neuropsychological testing.

The frontal assessment battery (FAB) is a bedside test of executive function. It takes less than 10 minutes to administer and a low score indicates executive dysfunction. To determine whether the FAB could detect the more severe subcortical dementia that is a feature of PSP and differentiate it from other bradykinetic rigid syndromes, we studied 17 patients with progressive supranuclear palsy (PSP); 11 with multiple system atrophy (MSA) and 12 with Parkinson's disease (PD). We compared FAB scores with the results of more detailed tests of executive and general cognitive function.FAB scores were significantly lower in PSP than in MSA or PD (p=0.02 and p<0.001) and were also found to be significantly lower in MSA than in PD (p=0.047). We divided the study group into those with an FAB score <15 and those with an FAB score>/=5, regardless of the clinical diagnosis. While 82% of the PSP group had FAB scores of <15, such scores were recorded in only 36% of the MSA and 8% of the PD groups. The lexical fluency and motor series subscores of the FAB discriminated 70% of the PSP, MSA and PD patients. The FAB scores correlated with tests of executive function, as well as with scores on the Mattis Dementia Rating Scale, the Mini Mental State Examination and other tests of general cognitive function. A stepwise regression analysis revealed that across the groups, among the variables that correlated with FAB scores, alternating semantic fluency accounted for 80% of FAB variance.These results suggest that the FAB is a valid and easily applicable bedside test to discriminate executive dysfunction in these three frequently confused bradykinetic rigid syndromes.

[An assessment of dysphagia using videofluorography in Parkinson's disease and progressive supranuclear palsy].

We assessed the oropharyngeal swallowing ability in 8 patients with Parkinson's disease (PD), 8 patients with progressive supranuclear palsy (PSP), and 10 age-matched healthy controls (CTL) using videofluorography (VF). In VF studies, PD and PSP patients demonstrated food pooling on the tongue, difficulty in bolus formation, and bolus falling into pharynx before swallow. PSP patients had a significantly longer delay in the pharyngeal phase and showed food falling into larynx more often than PD patients (p < 0.05). On measurement of swallowing time periods as proposed by Robbins et al., both patient groups showed significantly longer periods during many swallowing phases (P < 0.05) compared to those in the control group, but there were no significant differences between the PD and PSP groups. However, in PSP patients, the time for "transferring the food bolus from the oral cavity to pharynx" which we defined as a distinct stage was significantly longer (p < 0.05) than that in the PD group. We think that the difference in dysphagia characteristics between the two diseases arises from the variations in pathological changes in PSP, including those in the cerebral cortex, cerebellum, pons and medulla tegmentum in addition to the basal ganglia. Dystonia in the neck muscle also plays a role in dysphagia in PSP patients. Levodopa medication, changing the form of foods and training in rehabilitation techniques such as the chin down posture, supraglottic swallowing and ice-massage of the oral region are probably effective for dysphagia in PD patients. In patients with PSP, there are few research reports about the treatment of dysphagia. However, several dysphagia treatments seem to be useful depending on the abnormal patterns in the VF. Further studies are necessary to establish more effective treatments for dysphagia in PD and PSP.