Multimodal Preventive Trial for Alzheimer's Disease: MIND-ADmini Pilot Trial Study Design and Progress.

BACKGROUND: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer's disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. OBJECTIVES: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. METHODS: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. RESULTS: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. CONCLUSIONS: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).

Midlife improvements in financial situation are associated with a reduced dementia risk later in life: the CAIDE 30-year study.

OBJECTIVES: Perceived financial strain is associated with various health conditions, but it is unknown whether it is associated with an increased risk for dementia. The goal is to examine the associations between midlife perceptions of financial situation and dementia risk later in life. METHODS: Participants were derived from the Cardiovascular Risk Factors, Aging, and Dementia population-based cohort study (n = 2000) (between 1972 and 1987, baseline mean age 50 years) in Finland. Participants returned for two re-examinations in late life (in 1998 and 2005-2008, mean age 71 and 78 years). In this study, 1442 subjects that participated in at least one re-examination (mean total follow-up 25 years) were included in analyses. Financial strain was measured using two questions in midlife on perceptions of financial situation and perceptions of changes in financial situation. For each question, participants were categorized into three groups reporting improvement, worsening, or stability, with the latter set as the reference group. Analyses were adjusted for potential confounding factors. RESULTS: The group reporting better financial situation had a reduced risk for dementia (fully adjusted model: odds ratio (OR): 0.53, 95% confidence interval (CI): 0.33-0.86). In contrast, the group reporting worse financial situation did not have an increased risk for dementia (OR: 1.04, 95% CI: 0.53-2.02). Analyses on perceptions of current financial situation showed that the groups reporting satisfaction or dissatisfaction with financial situation did not differ in risk for dementia. CONCLUSION: This study is the first to show that midlife improvements in financial situation are associated with a reduced dementia risk later in life. Potential pathways related to stress reduction, improved lifestyle, and potential biological mechanisms are discussed.

The DeStress for Success Program: effects of a stress education program on cortisol levels and depressive symptomatology in adolescents making the transition to high school.

Various studies have shown that increased activity of the hypothalamic-pituitary-adrenal (HPA) axis can predict the onset of adolescent depressive symptomatology. We have previously shown that adolescents making the transition to high school present a significant increase in cortisol levels, the main product of HPA axis activation. In the present study, we evaluated whether a school-based education program developed according to the current state of knowledge on stress in psychoneuroendocrinology decreases cortisol levels and/or depressive symptoms in adolescents making the transition to high school. Participants were 504 Year 7 high school students from two private schools in the Montreal area. Adolescents of one school were exposed to the DeStress for Success Program while adolescents from the other school served as controls. Salivary cortisol levels and depressive symptomatology were measured before, immediately after as well as 3 months after exposure to the program. Measures of negative mood were obtained at baseline in order to determine whether adolescents starting high school with specific negative moods were differentially responsive to the program. The results show that only adolescents starting high school with high levels of anger responded to the intervention with a significant decrease in cortisol levels. Moreover, we found that adolescents who took part in the intervention and showed decreasing cortisol levels following the intervention (responders) were 2.45 times less at risk to suffer from clinical and subclinical depressive states three months post-intervention in comparison to adolescents who showed increasing cortisol levels following the intervention (nonresponders). This study provides the first evidence that a school-based program on stress is effective at decreasing cortisol levels and depressive symptomatology in adolescents making the transition to high school and it helps explain which adolescents are sensitive to the program and what are some of the characteristics of these individuals.

Depressive symptoms, cortisol, and cognition during human aging: the role of negative aging perceptions.

Depressive symptoms and memory impairments are associated with heightened stress hormone levels during aging. A factor that is related to memory deficits during aging is internalized negative aging stereotypes; the idea people have about the process of aging. In this study, we assessed the associations between internalized negative aging stereotypes, depressive symptoms, subjective and objective memory assessments, and cortisol concentration among older adults. Forty older adults aged between 58 and 85 years (18 females and 22 males; mean age ± SD: 71.25 ± 8.80 years) were assessed in this study. Measures of internalized negative aging stereotypes, depressive symptoms, and both subjective and objective memory performance were assessed. Salivary samples were obtained for measurement of cortisol concentration. Stepwise linear regressions were executed in our main analyses. Internalized negative aging stereotypes were associated with increased depressive symptoms and subjective memory complaints. No significant differences were observed for objective memory performance, or cortisol concentration. Internalized negative aging stereotypes are associated with increased depressive symptomatology and subjective complaints of memory; however, they do not predict increased cortisol concentration nor objective memory performance during aging. These results indicate that the mechanism underlying the association between internalized negative aging stereotypes and cognitive impairments may not be related to dysregulations of cortisol secretion among older adults.

Multi-element probabilistic collocation for sensitivity analysis in cellular signalling networks.

The multi-element probabilistic collocation method (ME-PCM) as a tool for sensitivity analysis of differential equation models as applied to cellular signalling networks is formulated. This method utilises a simple, efficient sampling algorithm to quantify local sensitivities throughout the parameter space. The application of the ME-PCM to a previously published ordinary differential equation model of the apoptosis signalling network is presented. The authors verify agreement with the previously identified regions of sensitivity and then go on to analyse this region in greater detail with the ME-PCM. The authors demonstrate the generality of the ME-PCM by studying sensitivity of the system using a variety of biologically relevant markers in the system such as variation in one (or many) chemical species as a function of time, and total exposure of a single chemical species.