Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions.

Post-traumatic stress disorder (PTSD) occurs in 5-10% of the population and is twice as common in women as in men. Although trauma exposure is the precipitating event for PTSD to develop, biological and psychosocial risk factors are increasingly viewed as predictors of symptom onset, severity and chronicity. PTSD affects multiple biological systems, such as brain circuitry and neurochemistry, and cellular, immune, endocrine and metabolic function. Treatment approaches involve a combination of medications and psychotherapy, with psychotherapy overall showing greatest efficacy. Studies of PTSD pathophysiology initially focused on the psychophysiology and neurobiology of stress responses, and the acquisition and the extinction of fear memories. However, increasing emphasis is being placed on identifying factors that explain individual differences in responses to trauma and promotion of resilience, such as genetic and social factors, brain developmental processes, cumulative biological and psychological effects of early childhood and other stressful lifetime events. The field of PTSD is currently challenged by fluctuations in diagnostic criteria, which have implications for epidemiological, biological, genetic and treatment studies. However, the advent of new biological methodologies offers the possibility of large-scale approaches to heterogeneous and genetically complex brain disorders, and provides optimism that individualized approaches to diagnosis and treatment will be discovered.

Purpose We sought to estimate the pooled current prevalence of posttraumatic stress disorder (PTSD) among rescue workers and to determine the variables implicated in the heterogeneity observed among the prevalences of individual studies. Methods A systematic review covering studies reporting on the PTSD prevalence in rescue teams was conducted following four sequential steps: (1) research in specialized online databases, (2) review of abstracts and selection of studies, (3) review of reference list, and (4) contact with authors and experts. Prevalence data from all studies were pooled using random effects model. Multivariate meta-regression models were fitted to identify variables related to the prevalences heterogeneity. Results A total of 28 studies, reporting on 40 samples with 20,424 rescuers, were selected. The worldwide pooled current prevalence was 10%. Meta-regression modeling in studies carried out in the Asian continent had, on average, higher estimated prevalences than those from Europe, but not higher than the North American estimates. Studies of ambulance personnel also showed higher estimated PTSD prevalence than studies with firefighters and police officers. Conclusions Rescue workers in general have a pooled current prevalence of PTSD that is much higher than that of the general population. Ambulance personnel and rescuers from Asia may be more susceptible to PTSD. These results indicate the need for improving pre-employment strategies to select the most resilient individuals for rescue work, to implement continuous preventive measures for personnel, and to promote educational campaigns about PTSD and its therapeutic possibilities.