Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay.

Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins. 4001 plasma proteins were measured in two groups of participants (discovery group = 516, replication group = 365) selected from the European Medical Information Framework for Alzheimer's disease Multimodal Biomarker Discovery study, all of whom had measures of amyloid. A panel of proteins (n = 44), along with age and apolipoprotein E (APOE) ε4, predicted brain amyloid deposition with good performance in both the discovery group (area under the curve = 0.78) and the replication group (area under the curve = 0.68). Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization. The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition

Consensus guidelines for lumbar puncture in patients with neurological diseases

Introduction Cerebrospinal fluid collection by lumbar puncture (LP) is performed in the diagnostic workup of several neurological brain diseases. Reluctance to perform the procedure is among others due to a lack of standards and guidelines to minimize the risk of complications, such as post-LP headache or back pain. Methods We provide consensus guidelines for the LP procedure to minimize the risk of complications. The recommendations are based on (1) data from a large multicenter LP feasibility study (evidence level II-2), (2) systematic literature review on LP needle characteristics and post-LP complications (evidence level II-2), (3) discussion of best practice within the Joint Programme Neurodegenerative Disease Research Biomarkers for Alzheimer's disease and Parkinson's Disease and Biomarkers for Multiple Sclerosis consortia (evidence level III). Results Our consensus guidelines address contraindications, as well as patient-related and procedure-related risk factors that can influence the development of post-LP complications. Discussion When an LP is performed correctly, the procedure is well tolerated and accepted with a low complication rate

Characteristics of subjective cognitive decline associated with amyloid positivity

Introduction: The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods: In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) ε4 carriership, and neuropsychiatric symptoms with amyloid positivity. Results: Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE ε4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages. Discussion: Next to age, setting, and APOE ε4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a \u201cHoly Grail\u201d of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APO\u3b54 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation

Perfil del cuidador informal asociado al manejo clínico del paciente con enfermedad de Alzheimer no respondedor al tratamiento sintomático de la enfermedad

Resumen: Introducción: Numerosos factores influyen en la satisfacción y la calidad de vida del cuidador informal del paciente con enfermedad de Alzheimer (EA) no respondedor. Entre ellos, destacan el curso de la enfermedad, el deterioro cognitivo y los trastornos conductuales de los pacientes, el grado de apoyo familiar y los factores inherentes al cuidador (tiempo de dedicación, estado psicológico y conocimiento de la enfermedad). El objetivo del trabajo fue determinar el perfil del cuidador informal del paciente con EA no respondedor, así como evaluar los diferentes factores que intervienen en su calidad de vida, carga soportada y satisfacción global con el tratamiento. Pacientes y métodos: Se llevó a cabo un estudio epidemiológico, prospectivo, multicéntrico y nacional que incluyó a 249 pacientes con EA no respondedores al tratamiento anticolinesterásico y a sus cuidadores. Se evaluó la calidad de vida del cuidador según el cuestionario de salud Short Form-36 (SF-36) y la carga asociada según escala de sobrecarga del cuidador Zarit, ambas validadas para España. La gravedad y la evolución de la patología se cuantificaron según el Clinical Dementia Rating (CDR) y el estado cognitivo mediante el Mini-Mental State Examination (MMSE). Resultados: La sobrecarga del cuidador mostró un incremento significativo en función del tiempo transcurrido desde el inicio del estudio, mientras que la satisfacción con el tratamiento aumentaba ligeramente con este mismo factor. La sobrecarga del cuidador resulta altamente correlacionada con el inventario CDR sobre sintomatología del paciente, tanto en visita inicial (p < 0,0001) como final (p = 0,0001). La satisfacción del cuidador con el tratamiento se vio afectada por el grado de cambio en el deterioro cognitivo padecido por el paciente entre las dos visitas (p = 0,021). Conclusiones: La satisfacción global con el tratamiento que declara el cuidador no se correlaciona con el cumplimiento terapéutico pero sí con los cambios en el deterioro cognitivo del paciente, factor que también influye sobre la carga soportada. Abstract: Introduction: Many factors influence the satisfaction and quality of life of informal caregivers of non-responder patients with Alzheimer disease (AD). Among these include, the course of the disease, cognitive impairment and behavioural disturbances of the patient, the level of family support and caregiver inherent factors such as, time commitment, psychological status and awareness of the disease. The aim of this work is to determine the profile of informal caregivers of non-responder AD patients and to evaluate the different factors that affect their quality of life, burden and overall satisfaction with treatment. Patients and methods: We carried out a prospective and multicentre study in Spain that included a total of 249 AD patients unresponsive to anticholinesterase treatment, and their informal caregivers. We evaluated caregivers’ quality of life with the SF-36 questionnaire and their associated burden with the Zarit scale, both validated for Spain. The severity and progression of the disease was quantified according to Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE). Results: Caregiver burden showed a significant increase with the time elapsed since the start of the study, while treatment satisfaction increased slightly with this factor. Caregiver burden is highly correlated with CDR scale on patient symptoms, both in the initial visit (p < .0001) and final visit (p = .0001). Caregiver satisfaction with treatment was mainly affected by the degree of change in cognitive deterioration experienced by the patient between the two visits (p = .021). Conclusions: Overall satisfaction with the treatment stated by the caregiver does not correlate with compliance to treatment, but it does so with the changes in patient's cognitive impairment, a factor that also influences caregiver's burden. Palabras clave: Enfermedad de Alzheimer, Cuidador informal, Tratamiento, Satisfacción, Calidad de vida, Sobrecarga del cuidador, Keywords: Alzheimer's disease, Informal caregiver, Treatment, Satisfaction, Quality of life, Caregiver burde

Assessment of the information provided by the medical specialist on Alzheimer's disease and that retained by the patient caregivers

Introduction: There is evidence of insufficient communication abilities by medical specialists as well as of the limited retentive capacities of patients with Alzheimer's disease (AD) and their caregivers. The main reasons for this include the personal limitations of the physician, as well as external, emotional and social-cultural factors associated with the patients and their caregivers.The aim of this study is to compare the clinical information on AD provided by the physicians and that perceived by caregivers and to assess factors associated with differences in perception. Patients and methods: We carried out an observational national multicentre study based on questionnaires assessing the information provided by the physician and that retained by the caregiver for 17 items of information. The study involved 61 researchers and included a total of 679 patients who met the selection criteria. We evaluated the factors associated with the difference in perception of the information that was transmitted. Results: Participating caregivers had a mean age of 57.2 ± 14.8 years, with an average care time of 27.6 ± 28.0 months. Approximately half (50.9%) were children of the AD patient and most lived in the same household (64.9%). Caregivers assigned significantly higher ratings to information on concept of disease, aetiology, pathogenesis, dosage and treatment recommendations and adherence, while doctors assigned significantly higher ratings to information related to demystification and correcting preconceived notions, possible complications, adverse events and/or iatrogenesis, family associations, and emotional/psychological support to caregivers (P < .05). Concordance between the information provided and that received was classified between poor and weak (inter-rater agreement ≤0.27). The degree of disease progression using the Global Deterioration Scale (GDS) was a factor significantly associated with professional-carer information discrepancy (P = .002). Conclusions: Many areas of information showed large differences in perception between physicians and caregivers of AD patients, which highlights the need to improve the communication process in order to achieve higher quality. Resumen: Introducción: Existen evidencias de la insuficiente capacidad informativa por parte de los especialistas médicos, así como de las dificultades retentivas de los pacientes con enfermedad de Alzheimer (EA) y de sus cuidadores. Entre las diversas causas figuran tanto las limitaciones personales del profesional como los determinantes externos, emocionales y socioculturales del paciente y de su cuidador.Contrastar la información clínica proporcionada por los médicos sobre la EA y la percibida por los cuidadores y evaluar los factores asociados a las diferencias de percepción. Pacientes y métodos: Se llevó a cabo un estudio observacional, multicéntrico y nacional mediante cuestionarios que evalúan la información suministrada por el médico y la retenida por el paciente en 17 aspectos informativos. Participaron 61 investigadores que incluyeron a un total de 679 pacientes que cumplían los criterios de selección. Se evaluaron los factores asociados a la diferencia de percepción sobre la información transmitida. Resultados: Los cuidadores participantes tenían una media de 57,2 ± 14,8 años, habiendo dedicado un tiempo medio como cuidadores de 27,6 ± 28,0 meses, y siendo el 50,9% hijos del paciente que mayoritariamente vivían en el mismo domicilio (64,9%). Los cuidadores valoraron significativamente mejor la información recibida sobre: concepto de la enfermedad, aspectos etiopatogénicos, posología y recomendaciones sobre el tratamiento y adherencia terapéutica, mientras que los médicos consideraron significativamente mejor la información referente a desmitificación y corrección de concepciones previas, posibles complicaciones, riesgos, efectos adversos y/o yatrogenia, asociaciones de familiares, y ayuda emocional/psicológica a cuidadores (p < 0,05). La concordancia en la información suministrada y la recibida fue entre pobre y débil (Kappa ≤ 0,27). El grado de evolución de la enfermedad (escala GDS) fue un factor significativamente asociado con la discordancia profesional-cuidador (p = 0,002). Conclusiones: Se apreciaron diferencias de percepción entre médicos y cuidadores de pacientes con EA para numerosos aspectos informativos, evidenciando la necesidad de mejorar el proceso comunicativo para optimizar su calidad. Keywords: Alzheimer's disease, Caregiver, Information, Education, Retention, Transmission, Palabras clave: Enfermedad de Alzheimer, Cuidador, Información, Educación, Retención, Transmisió

Evaluación de la información suministrada por el médico especialista sobre la enfermedad de Alzheimer y de la retención lograda por los cuidadores del enfermo

Resumen: Introducción: Existen evidencias de la insuficiente capacidad informativa por parte de los especialistas médicos, así como de las dificultades retentivas de los pacientes con enfermedad de Alzheimer (EA) y de sus cuidadores. Entre las diversas causas figuran tanto las limitaciones personales del profesional como los determinantes externos, emocionales y socioculturales del paciente y de su cuidador.Contrastar la información clínica proporcionada por los médicos sobre la EA y la percibida por los cuidadores y evaluar los factores asociados a las diferencias de percepción. Pacientes y métodos: Se llevó a cabo un estudio observacional, multicéntrico y nacional mediante cuestionarios que evalúan la información suministrada por el médico y la retenida por el paciente en 17 aspectos informativos. Participaron 61 investigadores que incluyeron a un total de 679 pacientes que cumplían los criterios de selección. Se evaluaron los factores asociados a la diferencia de percepción sobre la información transmitida. Resultados: Los cuidadores participantes tenían una media de 57,2 ± 14,8 años, habiendo dedicado un tiempo medio como cuidadores de 27,6 ± 28,0 meses, y siendo el 50,9% hijos del paciente que mayoritariamente vivían en el mismo domicilio (64,9%). Los cuidadores valoraron significativamente mejor la información recibida sobre: concepto de la enfermedad, aspectos etiopatogénicos, posología y recomendaciones sobre el tratamiento y adherencia terapéutica, mientras que los médicos consideraron significativamente mejor la información referente a desmitificación y corrección de concepciones previas, posibles complicaciones, riesgos, efectos adversos y/o yatrogenia, asociaciones de familiares, y ayuda emocional/psicológica a cuidadores (p < 0,05). La concordancia en la información suministrada y la recibida fue entre pobre y débil (Kappa ≤ 0,27). El grado de evolución de la enfermedad (escala GDS) fue un factor significativamente asociado con la discordancia profesional-cuidador (p = 0,002). Conclusiones: Se apreciaron diferencias de percepción entre médicos y cuidadores de pacientes con EA para numerosos aspectos informativos, evidenciando la necesidad de mejorar el proceso comunicativo para optimizar su calidad. Abstract: Introduction: There is evidence of insufficient communication abilities by medical specialists as well as of the limited retentive capacities of patients with Alzheimer disease (AD) and their caregivers. The main reasons for this include the personal limitations of the physician, as well as external, emotional and social-cultural factors associated with the patients and their caregivers.The aim of this study is to compare the clinical information on AD provided by the physicians and that perceived by caregivers and to assess factors associated with differences in perception. Patients and methods: We carried out an observational national multicentre study based on questionnaires assessing the information provided by the physician and that retained by the caregiver for 17 items of information. The study involved 61 researchers and included a total of 679 patients who met the selection criteria. We evaluated the factors associated with the difference in perception of the information that was transmitted. Results: Participating caregivers had a mean age of 57.2 ± 14.8 years, with an average care time of 27.6 ± 28.0 months. Approximately half (50.9%) were children of the AD patient and most lived in the same household (64.9%). Caregivers assigned significantly higher ratings to information on concept of disease, aetiology, pathogenesis, dosage and treatment recommendations and adherence, while doctors assigned significantly higher ratings to information related to demystification and correcting preconceived notions, possible complications, adverse events and/or iatrogenesis, family associations, and emotional/psychological support to caregivers (P<.05). Concordance between the information provided and that received was classified between poor and weak (inter-rater agreement ≤ 0.27). The degree of disease progression using the Global Deterioration Scale (GDS) was a factor significantly associated with professional-carer information discrepancy (P=.002). Conclusions: Many areas of information showed large differences in perception between physicians and caregivers of AD patients, which highlights the need to improve the communication process in order to achieve higher quality. Palabras clave: Enfermedad de Alzheimer, Cuidador, Información, Educación, Retención, Transmisión, Keywords: Alzheimer's disease, Caregiver, Information, Education, Retention, Transmissio

Profile of the informal carer associated with the clinical management of the Alzheimer's disease patient refractory to symptomatic treatment of the disease

Introduction: Many factors influence the satisfaction and quality of life of informal caregivers of non-responder patients with Alzheimer disease (AD). Among these include, the course of the disease, cognitive impairment and behavioural disturbances of the patient, the level of family support and caregiver inherent factors such as time commitment, psychological status and awareness of the disease. The aim of this work is to determine the profile of informal caregivers of non-responder AD patients and to evaluate the different factors that affect their quality of life, burden and overall satisfaction with treatment. Patients and methods: We carried out a prospective and multicentre study in Spain that included a total of 249 AD patients unresponsive to anticholinesterase treatment, and their informal caregivers. We evaluated caregivers’ quality of life with the SF-36 questionnaire and their associated burden with the Zarit scale, both validated for Spain. The severity and progression of the disease was quantified according to Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE). Results: Caregiver burden showed a significant increase with the time elapsed since the start of the study, while treatment satisfaction increased slightly with this factor. Caregiver burden is highly correlated with CDR scale on patient symptoms, both in the initial visit (p < .0001) and final visit (p = .0001). Caregiver satisfaction with treatment was mainly affected by the degree of change in cognitive deterioration experienced by the patient between the two visits (p = .021). Conclusions: Overall satisfaction with the treatment stated by the caregiver does not correlate with compliance to treatment, but it does so with the changes in patient's cognitive impairment, a factor that also influences caregiver's burden. Resumen: Introducción: Numerosos factores influyen en la satisfacción y la calidad de vida del cuidador informal del paciente con enfermedad de Alzheimer (EA) no respondedor. Entre ellos, destacan el curso de la enfermedad, el deterioro cognitivo y los trastornos conductuales de los pacientes, el grado de apoyo familiar y los factores inherentes al cuidador (tiempo de dedicación, estado psicológico y conocimiento de la enfermedad). El objetivo del trabajo fue determinar el perfil del cuidador informal del paciente con EA no respondedor, así como evaluar los diferentes factores que intervienen en su calidad de vida, carga soportada y satisfacción global con el tratamiento. Pacientes y métodos: Se llevó a cabo un estudio epidemiológico, prospectivo, multicéntrico y nacional que incluyó a 249 pacientes con EA no respondedores al tratamiento anticolinesterásico y a sus cuidadores. Se evaluó la calidad de vida del cuidador según el cuestionario de salud Short Form-36 (SF-36) y la carga asociada según escala de sobrecarga del cuidador Zarit, ambas validadas para España. La gravedad y la evolución de la patología se cuantificaron según el Clinical Dementia Rating (CDR) y el estado cognitivo mediante el Mini-Mental State Examination (MMSE). Resultados: La sobrecarga del cuidador mostró un incremento significativo en función del tiempo transcurrido desde el inicio del estudio, mientras que la satisfacción con el tratamiento aumentaba ligeramente con este mismo factor. La sobrecarga del cuidador resulta altamente correlacionada con el inventario CDR sobre sintomatología del paciente, tanto en visita inicial (p < 0,0001) como final (p = 0,0001). La satisfacción del cuidador con el tratamiento se vio afectada por el grado de cambio en el deterioro cognitivo padecido por el paciente entre las dos visitas (p = 0,021). Conclusiones: La satisfacción global con el tratamiento que declara el cuidador no se correlaciona con el cumplimiento terapéutico pero sí con los cambios en el deterioro cognitivo del paciente, factor que también influye sobre la carga soportada. Keywords: Alzheimer's disease, Informal caregiver, Treatment, Satisfaction, Quality of life, Caregiver burden, Palabras clave: Enfermedad de Alzheimer, Cuidador informal, Tratamiento, Satisfacción, Calidad de vida, Sobrecarga del cuidado