Neuropathological correlates of structural and functional imaging biomarkers in 4-repeat tauopathies.

Neurodegenerative dementia syndromes are characterized by spreading of pathological protein deposition along syndrome-specific neural networks. Structural and functional MRI measures can assess the integrity of these networks and have been proposed as biomarkers of disease progression for clinical trials. The relationship between in vivo imaging measures and pathological features, at the single subject level, remains largely unknown. Patient-specific maps of atrophy and seed-based intrinsic connectivity disruption, as compared to normal controls, were obtained for 27 patients subsequently diagnosed with progressive supranuclear palsy (n = 16, seven males, age at death 68.9 ± 6.0 years, imaging-to-pathology interval = 670.2 ± 425.1 days) or corticobasal degeneration (n = 11, two males, age at death 66.7 ± 5.4 years, imaging-to-pathology interval = 696.2 ± 482.2 days). A linear mixed effect model with crossed random effects was used to test regional and single-subject level associations between post-mortem regional measures of neurodegeneration and tau inclusion burden, on the one hand, and regional volume loss and seed-based intrinsic connectivity reduction, on the other. A significant association was found between tau inclusion burden and in vivo volume loss, at the regional level and independent of neurodegeneration severity, in both progressive supranuclear palsy [n = 340 regions; beta 0.036; 95% confidence interval (CI): 0.001, 0.072; P = 0.046] and corticobasal degeneration (n = 215 regions; beta 0.044; 95% CI: 0.009, 0.079; P = 0.013). We also found a significant association between post-mortem neurodegeneration and in vivo volume loss in both progressive supranuclear palsy (n = 340 regions; beta 0.155; 95% CI: 0.061, 0.248; P = 0.001) and corticobasal degeneration (n = 215 regions; beta 0.277; 95% CI: 0.104, 0.450; P = 0.002). We found a significant association between regional neurodegeneration and intrinsic connectivity dysfunction in corticobasal degeneration (n = 215 regions; beta 0.074; 95% CI: 0.005, 0.143; P = 0.035), but no other associations between post-mortem measures of tauopathy and intrinsic connectivity dysfunction reached statistical significance. Our data suggest that in vivo structural imaging measures reflect independent contributions from neurodegeneration and tau burden in progressive supranuclear palsy and corticobasal degeneration. Seed-based measures of intrinsic connectivity dysfunction showed less reliable predictive value when used as in vivo biomarkers of tauopathy. The findings provide important guidance for the use of imaging biomarkers as indirect in vivo assays of microscopic pathology.

The social and economic burden of frontotemporal degeneration.

OBJECTIVE: To quantify the socioeconomic burden of frontotemporal degeneration (FTD) compared to previously published data for Alzheimer disease (AD). METHODS: A 250-item internet survey was administered to primary caregivers of patients with behavioral-variant FTD (bvFTD), primary progressive aphasia, FTD with motor neuron disease, corticobasal syndrome, or progressive supranuclear palsy. The survey included validated scales for disease staging, behavior, activities of daily living, caregiver burden, and health economics, as well as investigator-designed questions to capture patient and caregiver experience with FTD. RESULTS: The entire survey was completed by 674 of 956 respondents (70.5%). Direct costs (2016 US dollars) equaled $47,916 and indirect costs $71,737, for a total annual per-patient cost of $119,654, nearly 2 times higher than reported costs for AD. Patients ≥65 years of age, with later stages of disease, and with bvFTD correlated with higher direct costs, while patients <65 years of age and men were associated with higher indirect costs. An FTD diagnosis produced a mean decrease in household income from $75,000 to $99,000 12 months before diagnosis to $50,000 to $59,999 12 months after diagnosis, resulting from lost days of work and early departure from the workforce. CONCLUSIONS: The economic burden of FTD is substantial. Counting productivity-related costs, per-patient costs for FTD appear to be greater than per-patient costs reported for AD. There is a need for biomarkers for accurate and timely diagnosis, effective treatments, and services to reduce this socioeconomic burden.

Rasch analysis of the carers quality of life questionnaire for parkinsonism.

OBJECTIVE: To assess the psychometric properties of the Carers Quality of Life Questionnaire for Parkinsonism using a Rasch modeling approach and determine the optimal cut-off score. METHODS: We performed a Rasch analysis of the survey answers of 430 carers of patients with atypical parkinsonism. RESULTS: All of the scale items demonstrated acceptable goodness of fit to the Rasch model. The scale was unidimensional and no notable differential item functioning was detected in the items regarding age and disease type. Rating categories were functioning adequately in all scale items. The scale had high reliability (.95) and construct validity and a high degree of precision, distinguishing between 5 distinct groups of carers with different levels of quality of life. A cut-off score of 62 was found to have the optimal screening accuracy based on Hospital Anxiety and Depression Scale subscores. CONCLUSION: The results suggest that the Carers Quality of Life Questionnaire for Parkinsonism is a useful scale to assess carers' quality of life and allows analyses requiring interval scaling of variables. © 2016 International Parkinson and Movement Disorder Society.

The Cure PSP Care Guide: A Telephonic Nursing Intervention for Individuals and Families Living With Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is a rare, progressive, and terminal neurodegenerative disease characterized by problems with ambulation, balance, mobility, vision, speech, swallowing, and behavior during the 7- to 10-year course of the illness. Substantial evidence in the nursing literature supports the benefits of patient education, self-management, chronic disease management, telehealth, and nurse navigation programs, which enhance patient and caregiver knowledge, improve day-to-day management by developing an awareness of resources, decrease dependence on services, and address caregiver needs. The Cure PSP Care Guide is a targeted telehealth nursing intervention aimed at providing knowledge, guidance, and resources to the vulnerable individuals and families living with PSP; identifying local resources; and building community. During the course of two telephone calls, individuals and their caregivers are assessed to develop a Cure PSP Care Guide designed to provide guidance along the trajectory. A knowledge assessment, self-efficacy scale, and Caregiver Strain Index are administered before and after the intervention to determine the program intervention effect. Caregiver knowledge assessments improved after the intervention, whereas strain scores were static. Qualitative data show the ability of the intervention to address caregiver needs for knowledge and support, daily management tips, and resource identification. The preliminary quantitative and qualitative data collected on this pilot project justify further exploration of the use of telehealth to remotely deliver nurse case management to the vulnerable individuals and families living with PSP.

[Progressive supranuclear palsy: living environment of the patients in Germany]. / Progressive supranukleäre Blickparese : Lebensumstände der Patienten in Deutschland.

The living environment of patients suffering from progressive supranuclear palsy (PSP) has attracted little interest so far. The aim of this study was to record environmental factors and patient care structures of PSP patients in Germany. In light of this aim 100 questionnaires consisting of 28 questions were distributed in the journal PSP-Rundschau (PSP Review) in February 2009. Up to August 2009, 69 completed questionnaires had been received for evaluation. The main results were a long period up to diagnosis (3.33 ± 2.5 years) and early clinical symptoms noted by many patients which could be used for the differential diagnosis between PSP and Parkinson's disease. In 87% of the cases the patients were cared for by relatives at home mostly without professional nursing home care.It is hoped that this investigation has shed more insight into the life and disease-related symptoms of patients with PSP and can provide valuable information for the understanding and treatment of this devastating disease.

Soft tissue manipulation: neuromuscular and muscle energy techniques.

Muscle rigidity and spasms occur with neurological disease and may contribute to contractures and shortening of muscle fibers that can interfere with motor behaviors, such as ambulation, or activities of daily living, such as combing hair, feeding or dressing. The neuromuscular technique (NMT) and muscle energy technique (MET) are nursing interventions that can reduce pain and muscle rigidity, lengthen muscle fibers and increase range of motion necessary for normal motor behavior. Nurses can use these techniques in patients with acute neurological diseases and those recovering in rehabilitation and long-term care settings. With some neurological diseases, muscle rigidity, increased muscle tone and muscle spasms reduce the range of motion of joints and the quality of movement. These changes often lead to contractures and impairments in performing daily tasks or ambulating, and thus, to loss of independence. Soft tissue manipulation can be used to reduce muscle tension and spasms, reduce pain and enhance the range of motion of joints whose function depends on the involved muscles. Soft tissue manipulation may also improve movement during specific tasks. Although the muscle relaxation achieved with manipulation techniques is primarily short-term, long-term effects occur. This article describes two techniques of soft tissue manipulation, their mechanisms of action, assessment and implementation. A case study is used to illustrate application of the techniques and possible long-term effects.

Progressive supranuclear palsy: managing the disabilities and providing nursing support.

Progressive Supranuclear Palsy is an uncommon progressive neurodegenerative disorder which may initially present as Parkinson's disease. It is characterized by an abnormality of voluntary eye movement, pseudobulbar palsy, axial dystonia/rigidity, postural instability, mental changes and bradykinesia. The symptoms may be present for up to 4.5 years before diagnosis with an average survival rate after diagnosis of about two years. However, the diagnosis is often make much sooner when the individual is assessed in a specialty Movement Disorder Clinic. At the time the diagnosis is made the individual and family will have no awareness of the devastating impact this illness will have on their lives. Often they do not understand the mechanisms of deterioration, nevertheless, they must learn how to manage the severe disabilities over a short time period. This article will address the symptomatology of Progressive Supranuclear Palsy, how it differs from Parkinson's disease, the pathophysiology, treatment, recommendations for managing the disabilities, providing nursing support, care for the caregiver, future care planning, the legal options of Enduring Power of Attorney, Trusteeship, Guardianship, Advance Directives, and consideration for autopsy.

"Learned helplessness" and the patient with progressive supranuclear palsy.

Progressive supra-nuclear palsy is a neurologically debilitating disease of unknown cause and with no effective treatment. Learned helplessness, a major cause of depression in the institutionalized elderly, is a feeling of worthlessness and powerlessness resulting in a decreased incentive to try. This article provides insight into these two problems and specific nursing interventions to enhance self care.

Autologous transplantation as a treatment for progressive supranuclear palsy.

Autologous transplantation of the adrenal gland has been attempted as a treatment for severe Parkinson's disease with limited success. Progressive supranuclear palsy (PSP), a more aggressive neurological entity of similar pathology, is due to a loss of dopamine in the caudate nucleus and putamen. The autologous transplant procedure has been performed on three PSP patients in an effort to restore dopamine to the caudate nucleus and putamen. The rationale and preliminary results of the transplantation procedure are reviewed in this article.

Progressive supranuclear palsy: nursing care implications.

Progressive supranuclear palsy (PSP) is an uncommon, but debilitating, neurological disease. Characterized by paralysis of eye movements, difficulty talking and swallowing, body trunk rigidity, gait ataxia, and dementia, the disease progresses rapidly over a 6-8 year time span. Death usually occurs from aspiration pneumonia. To provide meaningful care for the PSP patient and his/her family, the neuroscience nurse must first understand the disease pathophysiology, then the appropriate care interventions.