Returning research results that indicate risk of Alzheimer disease (AD) dementia—a disease for which no meaningful treatments or cure exist—to cognitively normal participants is controversial. AD is thought to begin many years before clinical signs and symptoms begin. During this time, individuals are cognitively normal but have biomarkers that indicate pathophysiological changes in the brain. With this study, we aim to evaluate the impact of returning research results on cognitively normal participants recruited from a longitudinal observational cohort on ageing at the Knight Alzheimer Disease Research Centre (Knight ADRC) at Washington University in St. Louis.

Our study uses a 2-year, delayed-start randomised clinical trial design. Participants are randomised to receive their research results either 2 weeks or 1 year after informed consent. This study was approved to recruit up to 450 participants with existing genetic and biomarker testing results from the Knight ADRC. During the study period, 260 individuals were eligible and approached for entry into the study. The primary cognitive outcomes are 1-year change in subjective cognitive score on the clinical dementia rating sum of box scores and the objective cognitive score on cognitive composite score. The primary psychosocial outcome is change in geriatric depression scale score 1 year after return of research results. The study was powered to answer primary outcomes with 140 participants (70 per study arm).

This study has been approved by the Washington University School of Medicine (WUSM) Institutional Review Board and the Human Research Protection Office. Results from these trials are shared through conferences and publications.

NCT04699786.

Although poor mental health among young people has been increasing in the past decades, many young people are reluctant to use traditional mental healthcare. To cater to the needs of young people, various youth-friendly treatment options have been developed. These include the youth-friendly health service (YFHS) standards put forth by the WHO in 2012 and the integrated youth services (IYS) for mental health developed in certain countries globally. However, no synthesis of the effect of these services on youth mental health has been conducted. The aim of the proposed study is to conduct a systematic review of the effect of mental health treatments conducted within YFHS and IYS clinics. The primary research question is what effect mental health interventions given at ‘youth-friendly’ clinics for treating mental health, such as IYS and YFHS, have on the mental health and quality of life (QoL) of young people?

A preliminary search for other reviews on the topic was conducted during the first half of 2024, after which a protocol of the present study was registered in PROSPERO. In May 2024, a search was carried out in the PubMed, PsycINFO, CINAHL and Web of Science databases, which gave references for 12 738 papers to be screened for inclusion in the review, and a follow-up search was carried out in April 2025, yielding a further 2182 references. For inclusion, studies must have participants between 12 and 25 years of age; interventions be given at clinics designed to be ‘youth-friendly’ or given at an IYS; control condition, if any, consisting of standard care or waiting list; outcomes must be mental health symptomology or QoL. To be included, studies must be published from 2012 and onwards. Screening of titles and abstracts in the initial search was carried out independently by two reviewers. Screening of studies found in the follow-up search and in the reference lists of included articles will be carried out in the same way. Data analysis of the initial search was conducted in the latter half of 2024, while final data analysis including the results from the follow-up search is ongoing. The Cochrane risk of bias assessment tools will be used to assess bias of included articles, and certainty of the evidence will be evaluated according to the GRADE methodology. A meta-analysis of the results will be performed if a sufficient amount of homogenous data is found; otherwise, a synthesis without meta-analysis will be conducted.

The proposed review may form a valuable synthesis of the state of the art of treatment options catering to young people. Investigating the effectiveness of YFHS or IYS in treating young people’s mental health may inform future directions for development and research. The present study does not need ethical approval, since only previously published, ethically approved data are used in the current study. The findings of the study will be disseminated through submissions to peer-reviewed journals and international conferences, as well as disseminated within the Swedish YFHS community.

ID nr CRD42024528687.