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BackgroundProgressive supranuclear palsy (PSP) is a neurodegenerative disease without approved therapies, and therapeutics are often tried off-label in the hope of slowing disease progression. Results from these experiences are seldom shared, which limits evidence-based knowledge to guide future treatment decisions.ObjectivesTo describe an open-label experience, including safety/tolerability, and longitudinal changes in biomarkers of disease progression in PSP-Richardson's syndrome (PSP-RS) patients treated with either salsalate or young plasma and compare to natural history data from previous multicenter studies.MethodsFor 6 months, 10 PSP-RS patients received daily salsalate 2,250 mg, and 5 patients received monthly infusions of four units of young plasma. Every 3 months, clinical severity was assessed with the Progressive Supranuclear Palsy Rating Scale (PSPRS), and MRI was obtained for volumetric measurement of midbrain. A range of exploratory biomarkers, including cerebrospinal fluid levels of neurofilament light chain, were collected at baseline and 6 months. Interventional data were compared to historical PSP-RS patients from the davunetide clinical trial and the 4-Repeat Tauopathy Neuroimaging Initiative.ResultsSalsalate and young plasma were safe and well tolerated. PSPRS change from baseline (mean ± standard deviation [SD]) was similar in salsalate (+5.6 ± 9.6), young plasma (+5.0 ± 7.1), and historical controls (+5.6 ± 7.1), and change in midbrain volume (cm3 ± SD) did not differ between salsalate (-0.07 ± 0.03), young plasma (-0.06 ± 0.03), and historical controls (-0.06 ± 0.04). No differences were observed between groups on any exploratory endpoint.ConclusionsNeither salsalate nor young plasma had a detectable effect on disease progression in PSP-RS. Focused open-label clinical trials incorporating historical clinical, neuropsychological, fluid, and imaging biomarkers provide useful preliminary data about the promise of novel PSP-directed therapies.

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.

BackgroundProgressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP.ObjectivesTo determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS.MethodsMulticenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity.ResultsThe earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity.ConclusionThe PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials.

Although the diagnosis of dementia still is primarily based on clinical criteria, neuroimaging is playing an increasingly important role. This is in large part due to advances in techniques that can assist with discriminating between different syndromes. Magnetic resonance imaging remains at the core of differential diagnosis, with specific patterns of cortical and subcortical changes having diagnostic significance. Recent developments in molecular PET imaging techniques have opened the door for not only antemortem but early, even preclinical, diagnosis of underlying pathology. This is vital, as treatment trials are underway for pharmacological agents with specific molecular targets, and numerous failed trials suggest that earlier treatment is needed. This article provides an overview of classic neuroimaging findings as well as new and cutting-edge research techniques that assist with clinical diagnosis of a range of dementia syndromes, with an emphasis on studies using pathologically proven cases.

Objective: To estimate prevalence of parkinsonism in the oldest-old and assess its association with age, gender, dementia, and falls. Background: Prevalence of parkinsonism increases with age up to age 85. However, whether it plateaus after age 90 is not clear, possibly due to the low number of these participants examined in previous studies or views that these features are attributable to the aging process. Methods: In-person clinical exams using modified UPDRS and Tinneti scales were analyzed in 966 participants from The 90+ Study, a population-based study of aging and dementia in people aged 90 and above. Parkinsonism was defined as meeting at least 2 of 4 core clinical criteria for parkinsonism (bradykinesia, resting tremor, rigidity, postural instability). One must be bradykinesia and all with at least mild severity. Dementia was diagnosed from in-person examinations by trained examiners using DSM-IV criteria. Results: The overall parkinsonism prevalence was 14.0[percnt]. People aged 90-94 had a prevalence of 12.4[percnt], significantly lower than those older than 95 (18.1[percnt]). Parkinsonism was significantly more frequent in participants with dementia (32.3[percnt]) compared to those who were cognitively-impaired-non-demented (7.9[percnt]) or normal (5.1[percnt]). Parkinsonism was more prevalent in those who reported a fall (15.6[percnt]) compared to non-fallers (11.5[percnt]) and was even higher in those with multiple falls in the last year (18.7[percnt]). Parkinsonism prevalence did not differ by gender. A multivariable logistic regression on gender, age, and dementia showed that dementia had the strongest association with parkinsonism. Conclusions: Despite analyses showing that prevalence of parkinsonism may plateau after age 90, it continued to increase in this study. Parkinsonism is associated with falls, frequent hospitalizations, and greater caregiver burden. Because higher fall rates and dementia are strongly associated with parkinsonism, early identification may lend opportunity to prevent adverse events and intervene in those with dementia. Study Supported by: The 90+ Study

This paper considers how parents are affected by and play a role in the lives of their young adult children. The years during which young people make the transition to adulthood has changed significantly in recent years--this transition now takes place over a longer period of time. We describe how young people experience these years; how they affect their parents and parent-child relationships; and how this time period is experienced by vulnerable youth.

With today's focus on academics, many teachers believe they have little time to focus on affective education. Indeed, many educators warn us that rather than no child being left behind, [...]

Examines three errors and learning difficulties found to be typical in general chemistry, gives the source of each problem, and presents a method of correcting each problem. Suggests using analysis of examination errors for the purpose of altering instruction for the improvement of student learning. (CW)