Design and Validation of a Clinical Outcome Measure for Adolescents and Adult Patients with Spinal Muscular Atrophy: SMA Life Study Protocol.

INTRODUCTION: The objective of this study is to develop a clinical tool for the evaluation and follow-up of adolescent and adult patients with 5q spinal muscular atrophy (SMA) and to design its validation. METHODS: This prospective, non-interventional study will be carried out at five centres in Spain and will include patients aged 16 years or older with a confirmed diagnosis of 5q SMA (biallelic mutation of the survival motor neuron 1 [SMN1] gene). A panel of experts made up of neurologists, physiatrists and Spanish patients' association (FundAME), participated in the design of the clinical tool. Physicians will administer the tool at three time points (baseline, 12 months and 24 months). Additionally, data from other questionnaires and scales will be collected. Once recruitment is achieved, an interim statistical analysis will be performed to assess its psychometric properties by applying Rasch analysis and classical statistical tests. RESULTS: The tool will consist of up to 53 items to assess functional status from a clinical perspective in seven key dimensions (bulbar, respiratory, axial, lower, upper, fatigability and other symptoms), which will be collected together with objective clinical measures (body mass index, forced vital capacity, pinch strength and 6-minute walk test). CONCLUSIONS: The validation of this tool will facilitate the clinical evaluation of adult and adolescent patients with SMA and the quantification of their response to new treatments in both clinical practice and research.

Attitudes of Neurologists Toward the Use of Biomarkers in the Diagnosis of Early Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) biomarkers reflect key elements of pathophysiology and improve the diagnostic process. However, their use in routine clinical practice is still limited. OBJECTIVE: We aimed to assess neurologists' barriers and enablers to early AD diagnosis using core AD biomarkers. METHODS: We conducted an online study in collaboration with the Spanish Society of Neurology. Neurologists answered a survey exploring their attitudes towards AD diagnosis using biomarkers in mild cognitive impairment (MCI) or mild AD dementia. Multivariate logistic regression analyses were conducted to determine the association between neurologists' characteristics and diagnostic attitudes. RESULTS: We included 188 neurologists with a mean age (SD) of 40.6 (11.3) years, 52.7% male. Most participants had access to AD biomarkers, mainly in cerebrospinal fluid (CSF) (89.9%,#x0025;, n = 169). The majority of participants (95.2%,#x0025;, n = 179) considered CSF biomarkers useful for an etiological diagnosis in MCI. However, 85.6% of respondents (n = 161) used them in less than 60% of their MCI patients in routine clinical practice. Facilitating patients and their families to plan for the future was the most frequent enabler for the use of biomarkers. Short consultation time and practicalities associated with the programming of a lumbar puncture were the most common barriers. A younger neurologist age (p = 0.010) and a higher number of patients managed weekly (p = 0.036) were positively associated with the use of biomarkers. CONCLUSION: Most neurologists had a favorable attitude to the use of biomarkers, especially in MCI patients. Improvements in resources and consultation time may increase their use in routine clinical practice.

Quality of Life and the Experience of Living with Early-Stage Alzheimer's Disease.

BACKGROUND: There is a need to better understand the experience of patients living with Alzheimer's disease (AD) in the early stages. OBJECTIVE: The aim of the study was to evaluate the perception of quality of life in patients with early-stage AD. METHODS: A multicenter, non-interventional study was conducted including patients of 50-90 years of age with prodromal or mild AD, a Mini-Mental State Examination (MMSE) score ≥22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5.-1.0. The Quality of Life in Alzheimer 's Disease (QoL-AD) questionnaire was used to assess health-related quality of life. A battery of self-report instruments was used to evaluate different psychological and behavioral domains. Associations between the QoL-AD and other outcome measures were analyzed using Spearman's rank correlations. RESULTS: A total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years and mean disease duration was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1). The mean QoL-AD score was 37.9 (4.5). Eighty-three percent (n = 124) of patients had moderate-to-severe hopelessness, 22.1% (n = 33) had depressive symptoms, and 36.9% (n = 55) felt stigmatized. The quality of life showed a significant positive correlation with self-efficacy and negative correlations with depression, emotional and practical consequences, stigma, and hopelessness. CONCLUSION: Stigma, depressive symptoms, and hopelessness are frequent scenarios in AD negatively impacting quality of life, even in a population with short disease duration and minimal cognitive impairment.

Design of a Non-Interventional Study to Validate a Set of Patient- and Caregiver-Oriented Measurements to Assess Health Outcomes in Spinal Muscular Atrophy (SMA-TOOL Study).

INTRODUCTION: There is a need to optimize the current clinical outcome measures in spinal muscular atrophy (SMA) incorporating patients' and caregivers' perspectives. The aim of this study is to evaluate the psychometric properties (validity, reliability and sensitivity to change) of a set of existing questionnaires and newly created items grouped in a "toolbox" to assess the impact of SMA on the physical, psychological and activities of daily living domains of the patient's life. METHODS: This non-interventional, prospective study will be conducted at 12 neuromuscular clinics specialized in the management of patients with SMA in Spain. An expert panel of pediatric and adult neurologists, rehabilitation physicians, and a patient representative participated in the study design and selected key disease dimensions to explore and their respective measurements: mobility-independence, fatigue and endurance, pain, fatigability, breathing and voice, sleep and rest, and vulnerability. Patients aged 2 years or older with a confirmed diagnosis of 5q-autosomal recessive SMA (genetic confirmation of homozygous deletion or heterozygosity predictive of loss of function of the SMN1 gene) will be recruited. PLANNED OUTCOMES: The development of robust outcome measures in collaboration with the patient community is essential to determine what is meaningful to patients and their caregivers. This study will provide us with a comprehensive set of tools to better capture the course of the disease and the response to treatments.