A cross-sectional study of α-synuclein seed amplification assay in Alzheimer's disease neuroimaging initiative: Prevalence and associations with Alzheimer's disease biomarkers and cognitive function.

INTRODUCTION: Alzheimer's disease (AD) pathology is defined by ß-amyloid (Aß) plaques and neurofibrillary tau, but Lewy bodies (LBs; 𝛼-synuclein aggregates) are a common co-pathology for which effective biomarkers are needed. METHODS: A validated α-synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 78 with LB-pathology confirmation at autopsy. We compared SAA outcomes with neuropathology, Aß and tau biomarkers, risk-factors, genetics, and cognitive trajectories. RESULTS: SAA showed 79% sensitivity and 97% specificity for LB pathology, with superior performance in identifying neocortical (100%) compared to limbic (57%) and amygdala-predominant (60%) LB-pathology. SAA+ rate was 22%, increasing with disease stage and age. Higher Aß burden but lower CSF p-tau181 associated with higher SAA+ rates, especially in dementia. SAA+ affected cognitive impairment in MCI and Early-AD who were already AD biomarker positive. DISCUSSION: SAA is a sensitive, specific marker for LB-pathology. Its increase in prevalence with age and AD stages, and its association with AD biomarkers, highlights the clinical importance of α-synuclein co-pathology in understanding AD's nature and progression. HIGHLIGHTS: SAA shows 79% sensitivity, 97% specificity for LB-pathology detection in AD. SAA positivity prevalence increases with disease stage and age. Higher Aß burden, lower CSF p-tau181 linked with higher SAA+ rates in dementia. SAA+ impacts cognitive impairment in early disease stages. Study underpins need for wider LB-pathology screening in AD treatment.

Raising awareness of sensory impairment among community nurses: a brief intervention in a remote island setting.

INTRODUCTION: The prevalence of sensory impairment that includes sight and/or hearing impairment is projected to rise worldwide given the strong correlation between sensory impairment, older age and the demographic structure of the global population. Sensory impairment and associated disability is thus a significant global health concern. The prevalence rates for sensory impairment in Scotland are significant: as more people live into older age and as the age distribution in rural areas is markedly different with a higher proportion of older people, the extent of sensory impairment in the rural population will increase proportionally. In rural areas community nurses have a key role in recognising sensory impairment and directing people to sensory services to reduce the debilitating impact of sensory impairment. However, there is limited evidence about the utility of educational interventions to enhance healthcare professionals' knowledge, skills and attitudes about sensory impairment and subsequent impact on referral practices. The aim of this study was to evaluate the impact of a brief educational intervention with community nurses. The educational intervention was a training workshop that included simulation practice, information on assessment and referral pathways. The study was conducted in a remote island community health setting in the Western Isles of Scotland. The study evaluated nurses' perceptions of the training on their knowledge, attitudes and practice. METHODS: Mixed method, longitudinal design was implemented in three phases. Phase 1 was a pre- and post-workshop questionnaire, phase 2 a postal questionnaire 3 months post-workshop and phase 3 a qualitative focus group interview 6 months post-workshop. Kirkpatrick's model of training evaluation provided a framework for data evaluation. RESULTS: A total of 41 community based healthcare professionals who were mostly nurses participated in the study. Participants described increased awareness of the potential for their patients to have a sensory impairment, greater understanding and empathy with patients who experience sensory impairment, more robust patient assessment to identify impairment, and increased likelihood to inform of, and refer to, sensory services. CONCLUSIONS: Community nurses are often well placed to identity disabilities and patients at risk of injury because of sensory impairment. Participation in simulation training can help to develop greater awareness of the impact of that sensory impairment. Knowledge of specialist services will increase the opportunities for referral to services and impact positively on the lives of older people living in rural settings. Provision of accessible education on sensory impairment for health and social care professionals can enhance care delivery to older people.

Association of CSF α-Synuclein Seeding Amplification Assay Results With Clinical Features of Possible and Probable Dementia With Lewy Bodies.

BACKGROUND AND OBJECTIVES: The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one of the several supportive features. α-Synuclein seeding amplification assays (αSyn-SAAs) may enhance diagnostic accuracy by detecting pathologic αSyn seeds in CSF. In this study, we examine how different clinical features associate with CSF αSyn-SAA positivity in a large group of clinically diagnosed participants with DLB. METHODS: Cross-sectional and longitudinal CSF samples from the multicentered observational cohort study of the DLB Consortium and similar studies within the Parkinson's Disease Biomarker Program, contributed by academic medical centers in the United States, underwent αSyn-SAA testing. Participants included those clinically diagnosed with DLB and 2 control cohorts. Associations between core DLB features and olfaction with αSyn-SAA positivity were evaluated using logistic regression. RESULTS: CSF samples from 191 participants diagnosed with DLB (mean age 69.9 ± 6.8, 15% female), 50 age-matched and sex-matched clinical control participants, and 49 younger analytical control participants were analyzed. Seventy-two percent (137/191) of participants with DLB had positive αSyn-SAAs vs 4% of the control groups. Among participants with DLB, those who were αSyn-SAA-positive had lower Montreal Cognitive Assessment scores (18.8 ± 5.7 vs 21.2 ± 5.2, p = 0.01), had worse parkinsonism on the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (33.8 ± 15.1 vs 25.6 ± 16.4, p = 0.001), were more likely to report RBD (114/133 [86%] vs 33/53 [62%], p < 0.0001), and had worse hyposmia on the University of Pennsylvania Smell Identification Test (UPSIT) (94/105 [90%] below 15th percentile vs 14/44 [32%], p < 0.0001). UPSIT percentile had the highest area under the curve (0.87, 95% CI 0.81-0.94) in predicting αSyn-SAA positivity and participants scoring at or below the 15th percentile of age and sex normative values had 18.3 times higher odds (95% CI 7.52-44.6) of having a positive αSyn-SAA test. Among 82 participants with longitudinal CSF samples, 81 (99%) had the same αSyn-SAA result for initial and follow-up specimens. DISCUSSION: A substantial proportion of clinically diagnosed participants with DLB had negative αSyn-SAA results. Hyposmia was the strongest clinical predictor of αSyn-SAA positivity. Hyposmia and αSyn-SAA may have utility in improving the diagnostic assessment of individuals with potential DLB. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that CSF αSyn-SAA distinguishes patients with clinically diagnosed DLB from normal controls.

Seed amplification assay results illustrate discrepancy in Parkinson's disease clinical diagnostic accuracy and error rates.

Parkinson's disease (PD) may be misdiagnosed due to the clinical overlap between PD and atypical parkinsonism. The utility of α-Synuclein (αSyn) Seed Amplification Assay (SAA) as a diagnostic indicator for PD has been reported in numerous studies, but never when administered as a validated clinical laboratory test. This study compares results from αSyn-SAA validation testing performed using well-characterized cohorts from two biorepositories to better understand the accuracy of PD clinical diagnosis. Blinded cerebrospinal fluid (CSF) specimens from a repository that included cohorts of subjects clinically diagnosed as PD or healthy controls, both with confirmatory dopamine transporter single-photon emission computed tomography (DAT SPECT) imaging, and blinded CSF specimens from a repository that included cohorts of subjects clinically diagnosed as PD or healthy controls based on clinical diagnosis alone, were tested as part of the validation studies for the diagnostic αSyn-SAA test (SYNTap® Biomarker Test). Measured αSyn-SAA test accuracy was 83.9% using clinical diagnosis as comparator, and 93.6% using clinical diagnosis with confirmatory DAT- SPECT imaging as comparator. The statistically significant discordance between accuracy determinations using specimens classified using different diagnostic inclusion criteria indicates that there is some symbiosis between dopamine-weighted imaging and αSyn-SAA results, both of which are associated with higher accuracy compared with the clinical diagnosis alone.

Changing the sheets: a new system to reduce strain during patient repositioning.

BACKGROUND: Manually repositioning patients puts healthcare providers at risk for injury; this may be reduced by using low-friction bedsheets. OBJECTIVES: The aim of this study was to evaluate the physical properties and the physiological measures of muscle activity and perceptual participant accounts between a new slider sheet system and traditional hospital bedsheet makeup (soaker pad with a jersey bottom sheet). METHOD: Surface electromyography was recorded from the arm and shoulder muscles of five healthcare providers executing a patient repositioning (boosting and turning) in a controlled laboratory setting to gain an indication of muscle activity required for two types of bedsheets (slider system and traditional sheet makeup). The Borg Scale was used to establish rating of perceived exertion for these repositioning tasks on the two types of bedsheet makeup. To evaluate the sheets independent of human interaction and contact, the physical resistive characteristics of the sheets were calculated by determining the coefficient of friction. RESULTS: Patient repositioning on traditional sheets, compared with the slider system, resulted in 16% greater electromyography burst numbers and 11% longer duration for both boosting and turning. Moreover, ratings of perceived exertion for repositioning patients on traditional sheets versus on slider sheets were more than double. The coefficient of friction of the traditional sheets was 65% less in the slider sheet system. DISCUSSION: This study suggests that manually repositioning patients on a low-friction slider system reduces muscular and perceived effort. Proper usage of this type of bedsheets may reduce the risks associated with musculoskeletal strain and injuries of the healthcare providers.

Physicians' knowledge of transdermal fentanyl.

BACKGROUND: Different opioids for use in the control of moderate to severe cancer pain have become widely available. More recently, sophisticated formulations such as transdermal patches have been developed. One example, transdermal fentanyl (TF), has characteristic pharmacokinetics and along with the other opioids, equivalency conversions are often made when changing from or to other opioids. AIM OF STUDY: To explore the knowledge of general practitioners (GPs), hospital consultants and oncologists about the pharmacology and use of TF in the management of moderate/severe cancer pain. METHOD: During 2001 and 2002 a questionnaire survey was carried out. A randomized selection of GPs, hospital consultants and oncologists (n=1167) from the UK and Ireland were sent a questionnaire and 576 (49%) were returned and evaluated. RESULTS: The results show doctors who had previously prescribed TF are more confident and knowledgeable about the indications and pharmacology of TF than doctors who had never prescribed TF. Overall knowledge and confidence in using TF was poor.