Axonal damage and astrocytosis are biological correlates of grey matter network integrity loss: a cohort study in autosomal dominant Alzheimer disease.

Brain development and maturation leads to grey matter networks that can be measured using magnetic resonance imaging. Network integrity is an indicator of information processing capacity which declines in neurodegenerative disorders such as Alzheimer disease (AD). The biological mechanisms causing this loss of network integrity remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and network integrity in mutation carriers (N=219) and noncarriers (N=136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Aß, Tau, synaptic (SNAP-25, neurogranin) and neuronal calcium-sensor protein (VILIP-1) preceded grey matter network disruptions by several years, while inflammation related (YKL-40) and axonal injury (NfL) abnormalities co-occurred and correlated with network integrity. This suggests that axonal loss and inflammation play a role in structural grey matter network changes. Key points: Abnormal levels of fluid markers for neuronal damage and inflammatory processes in CSF are associated with grey matter network disruptions.The strongest association was with NfL, suggesting that axonal loss may contribute to disrupted network organization as observed in AD.Tracking biomarker trajectories over the disease course, changes in CSF biomarkers generally precede changes in brain networks by several years.

[Are the prevalence and incidence of dementia declining?]. / Nemen de prevalentie en incidentie van dementie af?

The Framingham Heart Study showed a 35 per cent drop in new dementia cases in 25 years from the late 1970s to the early 2010s. The question that has been asked is: can we stop worrying about the dementia pandemic? We argue that dementia will remain a major health problem. In the Framingham Heart Study the largest decrease in incidence occurred in the early nineties and levelled off in later years. Higher educational levels and improved cardiovascular risk management may explain part of the decreased incidence. The latter justifies intensive treatment of cardiovascular risk factors. This may have to start at an earlier age than is currently the case since hypertension, obesity and diabetes are now prevalent at younger ages. Despite the decrease in dementia incidence, the absolute numbers of people with dementia will increase due to the aging population. Research on early diagnosis and new treatments for dementia therefore remains crucial.

Recovery in parents of children and adolescents who survived septic shock caused by Neisseria meningitidis: a cross-sectional study.

OBJECTIVES: To assess psychological distress, styles of coping and disease-related psychosocial limitations in parents of children and adolescents who survived meningococcal septic shock (MSS) 4-16 years ago. RESEARCH METHODOLOGY: An exploratory design using standardised questionnaires and interviews. SETTING: The psychological investigation took place in the department of Child and Adolescent Psychiatry of the ErasmusMC-Sophia Children's Hospital. MAIN OUTCOME MEASURES: 87 mothers and 77 fathers participated in this study. The General Health Questionnaire was used to assess parents' psychological distress; the Utrecht Coping List to assess styles of coping. A semi-structured disease-specific interview served to explore long-term disease-related psychosocial limitations for parents. RESULTS: MSS parents reported similar psychiatric symptoms and styles of coping in comparison to reference groups. Severity of illness and the child's age at time of illness were not significant predictors of parental psychological distress and styles of coping. The presence of somatic sequelae, cognitive or behavioural and emotional problems was not associated with the levels of parental psychiatric symptoms or styles of coping. The vast majority of parents reported no current disease-related psychosocial limitations due to the MSS. CONCLUSION: Parents of children who survived MSS show recovery. Nevertheless a minority still experiences emotional burden and disease-related limitations.

Long-term cognitive functioning in children and adolescents who survived septic shock caused by Neisseria meningitidis.

AIMS: To assess long-term cognitive functioning and its predictors, in children and adolescents who survived meningococcal septic shock (MSS) 4 to 16 years ago. METHODS: The Wechsler Intelligence Scale for Children-third edition was used to measure intellectual functioning and neuropsychological tests were used to measure attention, verbal memory, visual-motor integration, and executive skills. RESULTS: Overall, results of the total MSS sample (N=77) as to neuropsychological functioning were similar to those of normative reference groups. On social and practical reasoning and visual-motor integration, however, MSS children obtained poorer outcomes compared to normative data. Two children had mental retardation (estimated IQ<70) due to the MSS. The percentage of children with mental retardation or borderline intellectual functioning (15%) was similar to that in the general population (16%). Eighteen children (23%) had a z score<-2, indicating unusual poor functioning, on one or more domains of neuropsychological functioning (selective attention, sustained attention, and executive functioning). Compared to normative data, significantly more children had received special education services in the past. Older age at time of follow-up was the most important significant predictor of poorer long-term cognitive functioning. CONCLUSION: Overall, long-term outcomes as to cognitive functioning of the total MSS sample were similar to those of normative reference groups, but MSS children showed long-term impairments on social and practical reasoning, visual-motor integration, attention, and executive functioning. Older age at time of follow-up was a significant predictor.

Behavioural, emotional, and post-traumatic stress problems in children and adolescents, long term after septic shock caused by Neisseria meningitidis.

OBJECTIVES: To assess the occurrence of a wide range of behavioural, emotional, and post-traumatic stress problems in children and adolescents, long term after septic shock caused by Neisseria meningitidis (MSS). DESIGN: This study included 6- to 17-year-old patients who survived MSS and were admitted to the PICU of the Medical Centre between 1988 and 2001. To assess behavioural, emotional, and post-traumatic stress problems, the Child Behaviour Checklist (CBCL), the Teacher's Report Form (TRF), and the Youth Self-Report (YSR) were used. METHODS: Parents of 89 MSS children, aged 6-17 years, completed the CBCL. Teachers of 65 same-aged MSS children completed the TRF, and 45 11- to 17-year-old MSS children completed the YSR. These data were compared with those from the normative reference groups. RESULTS: Overall, the proportions of MSS children scoring in the deviant range for problem behaviour were comparable to the proportions in the reference groups, according to parents', teachers', and self-reports. As to the level of emotional and behavioural problems, mothers of the MSS children reported more somatic complaints regarding their children in comparison with the reference groups. Severity of illness was not a significant predictor of behavioural, emotional, and post-traumatic stress problems. Age at the time of illness was a significant predictor of behavioural, emotional, and post-traumatic stress problems in MSS children, indicating that the younger the child at the time of illness, the more problems were reported by parents at follow-up. CONCLUSION: Overall, the results showed long-term behavioural, emotional, and post-traumatic stress outcomes for MSS children, which were comparable to those in the general population.