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Subjective cognitive decline (SCD) in cognitively normal elderly individuals is now recognized as a pre-mild cognitive impairment (pre-MCI) at-risk state of Alzheimer’s disease (AD) dementia. It will be a major target condition for AD prevention trials in the future. Recently, an international working group has consented a general research framework for SCD in the context of preclinical AD. Currently, however, comparability of SCD samples across different research sites is poor and the frequency of preclinical in SCD samples is highly divers. This is mainly due to the lack of a harmonized protocol for SCD definition and assessment. The design of a harmonized SCD protocol is therefore the crucial next step before applying the highly attractive condition of SCD in large scale AD prevention in trials and in health care. In this study, existing memory clinic samples of subjects with SCD and with available biomarkers for SCD from three European countries will be analyzed with regard to features of SCD that indicate preclinical AD evidenced by biomarkers. Based on these existing samples and on additional data from the literature a harmonized transnational protocol for SCD case definition and assesment will be created, which aims at achieving highly comparable rates of enrichment for preclinical AD in SCD subjects across different European sites. This protocol will be validated in a multicenter pilot study in the three participating countries with a total of n=90 SCD individuals. The enrichment rate for preclinical AD achieved by the harmonized protocol will be assessed with CSF AD biomarker and amyloid-PET imaging in these subjects. It is expected to generate a protocol for SCD case definition and assessment which achieves robust and comparable enrichment rates for preclinical AD across research sites in different European countries.

Individuals with SCD, who seek medical help, are particularly motivated to engage in dementia prevention actions. Most heath care systems, however, will not reimburse long term prevention interventions, if applied by professionals, in largely unimpaired individuals, such as subjects with SCD. Self-applied, personalized, web-based guides for lifestyle modification, however, are an attractive approach to provided structured dementia prevention to these subjects. In this proposal an internet platform will be designed, which provides a self-applied, personally tailored guide for lifestyle modification in SCD. The content will be generated by literature search and meta-analyses, but also by focus groups, which include SCD individuals. This will ensure that patient related needs, views and obstacles in usage of such tools are identified. The design of the internet platform will follow and iterative process with developers and users. This development process will include users from all three participating sites in order to identify and address language and culture specific aspects of relevance for successful impelmentation in the future. The internet platform will be offered to the participants of the SCD pilot trial (see above) at each site in oder to integrate their feedback on usability and acceptance in the development process.

The deliverables of the project are (1) a transnational harmonized protocol for SCD case definition, with predicable rates of enrichment for AD, which is the basis for transnational AD prevention trials in SCD, and (2) an internet platform for self-applied lifestyle modification with the aim of dementia prevention in subjects fulfilling the SCD criteria.

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