The Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) score as a predictor for cognitive decline and potential surrogate outcome in the FINGER lifestyle randomized controlled trial.

BACKGROUND AND PURPOSE: The complex aetiology of Alzheimer's disease suggests prevention potential. Risk scores have potential as risk stratification tools and surrogate outcomes in multimodal interventions targeting specific at-risk populations. The Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) was tested in relation to cognition and its suitability as a surrogate outcome in a multidomain lifestyle randomized controlled trial, in older adults at risk of dementia. METHODS: In this post hoc analysis of the Finnish Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), ANU-ADRI was calculated at baseline, 12, and 24 months (n = 1174). The association between ANU-ADRI and cognition (at baseline and over time), the intervention effect on changes in ANU-ADRI, and the potential impact of baseline ANU-ADRI on the intervention effect on changes in cognition were assessed using linear mixed models with maximum likelihood estimation. RESULTS: A higher ANU-ADRI was significantly related to worse cognition, at baseline (e.g., estimate for global cognition [95% confidence interval] was -0.028 [-0.032 to -0.025]) and over the 2-year study (e.g., estimate for 2-year changes in ANU-ADRI and per-year changes in global cognition [95% confidence interval] was -0.068 [-0.026 to -0.108]). No significant beneficial intervention effect was reported for ANU-ADRI, and baseline ANU-ADRI did not significantly affect the response to the intervention on changes in cognition. CONCLUSIONS: The ANU-ADRI was effective for the risk prediction of cognitive decline. Risk scores may be crucial for the success of novel dementia prevention strategies, but their algorithm, the target population, and the intervention design should be carefully considered when choosing the appropriate tool for each context.

Could Country-Level Factors Explain Sex Differences in Dementia Incidence and Prevalence? A Systematic Review and Meta-Analysis.

BACKGROUND: Despite rising interest in sex differences in dementia, it is unclear whether sex differences in dementia incidence and prevalence are apparent globally. OBJECTIVE: We examine sex differences in incidence and prevalence of Any dementia, Alzheimer's disease (AD), and vascular dementia (VaD), and evaluate whether country-level indicators of gender inequality account for differences. METHODS: Systematic review with meta-analysis was used to obtain estimates of incidence and prevalence of Any dementia, AD, and VaD using random effects meta-analysis, and population-based studies with clinical or validated dementia measures. Meta-regression was used to evaluate how country-specific factors of life expectancy, education, and gender differences in development, unemployment, and inequality indices influenced estimates. RESULTS: We identified 205 eligible studies from 8,731 articles, representing 998,187 participants across 43 countries. There were no sex differences in the incidence of Any dementia, AD, or VaD, except in the 90+ age group (women higher). When examined by 5-year age bands, the only sex difference in prevalence of Any dementia was in the 85+ group and there was no sex difference in VaD. AD was more prevalent in women at most ages. Globally, the overall prevalence of dementia in adults 65 + was higher for women (80.22/1000, 95% CI 62.83-97.61) than men (54.86/1000, 95% CI 43.55-66.17). Meta-regression revealed that sex differences in Any dementia prevalence were associated with gender differences in life expectancy and in education. CONCLUSION: Globally, there are no sex differences in age-specific dementia incidence, but prevalence of AD is higher in women. Country-level factors like life expectancy and gender differences in education may explain variability in sex differences.

No clear associations between subjective memory concerns and subsequent change in cognitive function: the PATH through life study.

The literature on subjective memory concerns (SMC) as a predictor for future cognitive decline is varied. Furthermore, recent research has pointed to additional complexity arising from variability in the experience of SMC themselves (i.e. whether they are remitting or sustained over time). We investigated the associations between SMC and objectively measured cognition in an Australian population-based cohort. Four waves (4-year intervals between waves) of data from 1236 participants (aged 62.4 ± 1.5 years, 53% male) were used. We categorized participants as experiencing SMC, when they indicated that their memory problems might interfere with their day-to-day life and/or they had seen a doctor about their memory. SMC was categorized as "no" reported SMC, "remitting", "new-onset" or "sustained" SMC. Cognitive assessment of immediate and delayed recall, working memory, psychomotor speed, attention and processing speed were assessed using a neuropsychological battery. Eighteen percent of participants were characterised as having SMC: 6% (77) "remitting", 6% (77) "new-onset" and 6% (69) "sustained" SMC. There was no consistent evidence for an association between SMC and subsequent decline in cognition. However, SMC was associated with poorer performance on contemporaneous tasks of attention and processing speed compared to "no" SMC. Asking about SMC may indicate a current decline in cognitive function but, in this sample at least, did not indicate an increased risk of future decline. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-022-00694-2.

Examining longitudinal associations between self-reported depression, anxiety and stress symptoms and hair cortisol among mothers of young children.

BACKGROUND: Maternal mental health is critically important given its impacts on both women's and children's outcomes. Hair cortisol concentrations (HCC) may provide insight into physiological processes underpinning mental health. This study investigated associations between mothers' self-reported mental health symptoms and their HCC at 1, 2 and 3 years postpartum. METHODS: Longitudinal study of Australian mothers recruited for their experience of adversity in pregnancy ('right@home' trial, N=722). Mental health symptoms were self-reported using the Depression, Anxiety and Stress Scales (DASS). Associations between DASS total and subscale scores and HCC were estimated using linear regression and generalized estimating equation (GEE) models, examining associations: at each age; across all ages (multivariate GEE); and with persistence of high symptom severity. Missing data were addressed using multiple imputation. RESULTS: 546/722 (76%) women provided at least one hair sample (71% at 1, 61% at 2, 49% at 3 years). Associations between DASS total or subscale scores and HCC were not evident across time points. Only dichotomized high depression symptom severity was associated with higher HCC in the GEE models (ß=0.12, p=0.04). There was no evidence of associations between persistence of high DASS symptom severity and HCC at 3 years. LIMITATIONS: The DASS measured self-reported symptoms for the preceding week whereas HCC captured average cortisol over three months. Associations amongst mothers experiencing adversity may not represent patterns in the general population. CONCLUSIONS: Considered in context with existing literature, these findings suggest that HCC provides limited insight into the mental health of mothers experiencing adversity across the early postpartum years.

The Psychometric Properties of the Visual Analogue Scale Applied by an Observer to Assess Procedural Pain in Infants and Young Children: An Observational Study.

PURPOSE: The Visual Analogue Scale applied by an observer (VASobs) is widely used to quantify pain but the evidence to support validity is poor. The aim of this study was to evaluate the psychometric and practical properties of the VASobs used to assess procedural pain in infants and young children. DESIGN AND METHODS: In an observational study, 26 clinicians applied the VASobs independently to video segments of 100 children aged six to 42 months undergoing a procedure to generate pain and distress scores. Each video segment was scored by four randomly selected reviewers. RESULTS: Reliability for pain scores was poor to fair (ICC 0.35 to 0.55) but higher for distress scores (ICC 0.6 to 0.89). At a cut-off score of 3, sensitivity and specificity were 84.7% and 95.0%, respectively for pain and 91.5% and 77.5% respectively for distress. Linear mixed modelling confirmed responsiveness. An increase in pain scores (regression slope 4.95) and distress scores (regression slope 5.52) across phases (baseline to procedure) was seen for painful procedures. The correlation between VASobs pain and FLACC scores was good (r = 0.74) and correlations between VASobs distress and FLACC scores were excellent (r = 0.89). CONCLUSION: VASobs was easily applied and preferred by clinicians. Despite evidence of sensitivity and responsiveness to pain, the reliability results were poor, and this scale cannot be recommended for use. PRACTICE IMPLICATIONS: The results of this study prevent recommending the VASobs for assessing procedural pain in infants and young children for clinical or research purposes.

Rotavirus specific maternal antibodies and immune response to RV3-BB rotavirus vaccine in central java and yogyakarta, Indonesia.

BACKGROUND: Placental or breast milk maternal antibodies can potentially reduce oral rotavirus vaccine efficacy in developing countries. We aimed to examine the relationship between the level of rotavirus specific immunoglobulin A (IgA) and neutralising antibodies (NA) in colostrum and breast milk and cord IgG, with cumulative vaccine take following one and three doses of oral RV3-BB rotavirus vaccine within a Phase IIb trial in Indonesia. METHODS: 196 infants received three doses of RV3-BB in a randomized, double-blinded trial, using a neonatal schedule (first dose at 0-5 days of age, n = 61), an infant schedule (first dose at ~ 8 weeks of age, n = 67) or placebo (n = 68). Rotavirus specific IgA and NA in colostrum and breast milk, rotavirus specific cord IgG, Serum IgA and stool excretion were measured. RESULTS: There was little evidence of an association between IgA in colostrum or breast milk and cumulative vaccine take after three doses in the neonatal or infant groups. In the neonatal group, there was a negative association between IgG titre in cord blood and cumulative vaccine take (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.92-1.00; p = 0.03) and serum IgA response (OR 0.94; 95%CI 0.89-0.99; p = 0.02) after one dose of vaccine, which were not evident after three doses in the neonatal or infant groups. CONCLUSIONS: Amongst Indonesian infants we did not find an association between IgA in colostrum or breast milk and vaccine take after 3 doses of RV3-BB vaccine. Maternal rotavirus antibodies in breast milk appear to have minimal impact on RV3-BB vaccine take when administered with a short delay in breast-feeding in settings with a high rotavirus disease burden.

The Psychometric Properties of the FLACC Scale Used to Assess Procedural Pain.

The Face, Legs, Activity, Cry, and Consolability (FLACC) scale is one of the most commonly and widely used behavioral observation pain scales. The aim of this study was to test the psychometric and practical properties of the FLACC scale to quantify procedural pain in infants and young children. Twenty-six clinicians independently applied the FLACC scale to segments of video collected from 100 children aged 6 to 42 months undergoing a procedure. Video segments were scored by 4 reviewers. Inter- and intrarater reliability coefficients were high (.92 and .87, respectively). Linear mixed modeling confirmed scale responsiveness (differences in difference between FLACC scores across phases for painful versus nonpainful procedures was 4.2, 95% confidence interval = 3.67-4.81). Sensitivity and specificity were 94.9% and 73.5%, respectively, at a cutoff of 2. However, the mean difference across phases for children with baseline scores >3 was much lower than for children with scores <3, P = .0001. Correlations between FLACC and Visual Analog Scale observer pain and distress were good (r = .74 and r = .89, respectively). This study supports the reliability and sensitivity of the FLACC scale for procedural pain assessment. However, the circumstances of procedures interfered with application of the scale and the findings question the capacity of the scale to differentiate between pain- and nonpain-related distress. PERSPECTIVE: This article provides evidence that the FLACC scale is reliable and sensitive to pain for procedural pain assessment. Concerns remain about specificity and scale design. Identification of a scale valid for this purpose is needed to provide a platform for improved procedural pain management in infants and young children.