ABSTRACT
INTRODUCTION: Amyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)-ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE-ε4 carriership is associated with EC disruptions in cognitively normal individuals. METHODS: A total of 261 healthy middle-aged to older adults (mean age 56.6 years) were divided into high-risk (APOE-ε4 carriers) and low-risk (noncarriers) groups. EC was computed from resting-state functional MRI data. Clusters of between-group differences were assessed with a permutation-based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed. RESULTS: Decreased EC in the visual cortex was associated with APOE-ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail-making and 15-object recognition tests. CONCLUSION: Our findings suggest that the APOE-ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease-related pathology. These differences were too subtle in healthy elderly to use EC for single-subject prediction of APOE genotype.
Subject(s)
Alzheimer Disease/genetics , Apolipoprotein E4/genetics , Brain Mapping/methods , Brain/diagnostic imaging , Cognition , Female , Genotype , Humans , Longitudinal Studies , Magnetic Resonance Imaging/methods , Male , Middle Aged , Reference Values , SpainABSTRACT
Introducción: La enfermedad de Alzheimer (EA) involucra a colectivos diversos de profesionales y cuidadores. Las actitudes y necesidades de formación en diagnóstico temprano, tratamiento, síntomas conductuales, recursos sociosanitarios y aspectos legales o éticos son desconocidas. Métodos: Estudio observacional transversal tipo encuesta dentro del proyecto kNOW Alzheimer, iniciativa de la SEN, SEGG, SEMERGEN, SEFAC y CEAFA mediante cuestionarios específicos. Cada sociedad invitó a todos sus miembros a cumplimentarlos a través de www.knowalzheimer.com. Resultados: Participaron 114 neurólogos, 113 geriatras, 275 médicos de atención primaria, 328 farmacéuticos y 858 cuidadores. Los retrasos en el diagnóstico se originan en pacientes y cuidadores, el sistema y en los profesionales, que carecen de medios o malinterpretan síntomas tempranos. Persiste el uso del término 'demencia senil'. Profesionales y cuidadores perciben buena eficacia del tratamiento. Se apuesta por el diagnóstico y tratamiento en fase pre-demencia. Hay déficit de formación en el manejo de la conducta. Los profesionales afirman que informan pero los cuidadores se sienten desinformados. Los cuidadores desean conocer cuanto antes si ellos o un familiar padecen Alzheimer. Los síntomas conductuales y la necesidad de restringir actividades son fuentes de sobrecarga. Los farmacéuticos pueden contribuir a la detección y manejo, pero precisan de formación amplia. Hay necesidad de formación en aspectos legales, bioéticos, recursos y acceso a la investigación. Conclusiones: Este proyecto ha permitido obtener información sobre actitudes y dudas de los colectivos involucrados en la atención a la EA, necesidades de formación y puntos de mejora (AU)
Background: Alzheimers disease (AD) involves different groups of professionals and caregivers. Their attitudes and needs of training in early diagnosis, treatment, behavioral symptoms, resources, social and legal or ethical aspects are unknown. Methods: Survey study within the project 'kNOW Alzheimer', a SEN, SEGG, SEMERGEN SEFAC and CEAFA initiative, through specific questionnaires. Each Society invited all its members to complete them through www.knowalzheimer.com. Results: Participants were 114 neurologists, geriatricians 113, 275 primary care physicians, 328 pharmacists and 858 caregivers. Delays in diagnosis arise in patients and caregivers, the system and the professionals, who lack the means or misinterpreted early symptoms. The term 'senile dementia' is still in use. Professionals and caregivers perceived good efficacy of treatment. Professionals advocate for diagnosis and treatment in the pre-dementia stage. There is a need for training in behavior management. Practitioners claim they inform but caregivers feel uninformed. Caregivers want to know as soon as possible if they or a family member suffers from AD. Behavioral symptoms and the need to restrict activities are sources of overload. Pharmacists can contribute to detection and management, but require extensive training. There is a need for training on legal aspects, bioethics, resources and access to research. Conclusions: This project has yielded information on attitudes and doubts of the collectives involved in AD care, their training needs and points of improvement (AU)
