Key take-aways:
- Mild cognitive impairment (MCI) is a stage of decline in cognitive function greater than normal for a person's age and education, not severe enough to impair daily function – but it can progress.
- Around one third of people with cardiovascular disease (CVD) also have MCI, yet MCI is undiagnosed in 50-80% of these cases.
- The central aim of the EU's DORIAN GRAY project is to untangle this MCI-CVD connection, reduce the burden of disease at older ages and prolong survival.
Brescia, Italy – 27 February 2025: A major new project, DORIAN GRAY, funded by the European Union (EU) and led by the University of Brescia and partners including the European Society of Cardiology (ESC) – aims to uncover the links between cardiovascular disease (CVD) and mild cognitive impairment (MCI). The ambition of the DORIAN GRAY project aligns with the EU's Horizon Europe strategic plan for 2021-2024, emphasising a holistic approach to disease prevention and the promotion of physical and mental health.
DORIAN GRAY will last five years (with the official start date 1 January 2025) and has a budget of 11 million euros distributed across 24 partners. It will be formally launched with an event at the University of Brescia, Italy, on February 27.
Around one third of people living with CVD also have MCI, yet MCI is undiagnosed in an estimated 50-80% of these cases. The association between the two conditions extends beyond merely sharing well-established risk factors and implies that CVD itself may contribute to MCI, which refers to a stage of cognitive decline greater than normal for a person's age and education, but not severe enough to impair daily function. Conversely, dementia is characterised by a progressive decline in cognitive abilities and the ability to live independently.
The overarching ambition of DORIAN GRAY is to uncover the mechanisms bridging MCI and CVD, and develop an integrated approach, which aims to promote resilience and improve overall health in the ageing population. It will start with the analysis of data available in patients with CVD, such as heart failure (HF), in which mechanisms leading to MCI are enhanced, and thereafter the factors aggravating the onset and progression of cognitive impairment in the general population with cardiovascular risk factors (CVRF) will be defined.
"For years, Alzheimer's Disease (AD) and cerebrovascular dementia were viewed as separate entities. Recent research suggests they may represent a continuum, with overlapping pathways favouring either vascular or parenchymal β-amyloid deposition," explains DORIAN GRAY scientific coordinator Dr Riccardo Proietti of the University of Liverpool, UK. "CVD not only shares risk factors with cognitive impairment (CI) but may also contribute to it, through mechanisms like chronic hypoperfusion, infarcts, and arterial stiffness. However, a unifying theory remains elusive due to the lack of reliable biomarkers for early diagnosis and risk stratification in MCI patients with CVD. The goal of DORIAN GRAY is to develop a neurobiology-based hypothesis linking MCI to CVD, using biomarkers for clinical assessment to inform joint health policies for prevention, while also developing an innovative digital tool that can be used for cognitive enhancement."
The project will integrate real-world data from multiple sources (e. g., smartwatches, smartphones, tablets) and leverage artificial intelligence (AI) alongside with clinical variables to enable risk stratification and personalised treatment. This approach can be applied to primary prevention (risk stratification for MCI), secondary prevention (slowing progression toward dementia), and tertiary prevention (reducing the severity of MCI).
This will, in turn, enable the early identification of patterns or 'fingerprints' of potential MCI progression, and introduces a paradigm shift in healthcare, applicable to other non-communicable diseases. A groundbreaking feature of the project is the use of a medical avatar, an innovative technology with vast, yet largely untapped potential in healthcare. In DORIAN GRAY, avatar-based coaching exergaming (ABCE) — a technology-driven physical activity — will serve as both a cognitive enhancement tool in the exergame component and a lifestyle intervention in the coaching system. Instead of just offering explicit behavioural instructions, ABCE shapes all aspects of a user's life comprehensively increasing their awareness on physical and mental well-being, positively impacting healthy ageing.
Key parts of the project include:
- Use of data from over 300,000 individuals across six countries to develop an AI model for predicting MCI risk and predisposition
- Co-design and development of an effective digital coaching system (CS), to facilitate the adoption of healthy lifestyle changes
- Co-design and development of the avatar-based exergaming (ABE) solution, incorporating structured physical and cognitive exercises within a role-playing game-like environment
- Delivery of a pilot randomised-controlled trial (RCT) in patients with heart failure and MCI to test the feasibility and effectiveness of the avatar-based coaching exergaming ABCE intervention
- Generation of a Health Technology Assessment (HTA) report, based on the results of an implementation clinical study conducted in four clinical centres across Europe
- Communication of the project outcomes to patients, health care practitioners, health policymakers, and the scientific community, ensuring broad engagement with key stakeholders.
DORIAN GRAY will have a substantial impact on various subgroups of the European population, including patients with CVD and individuals at high risk of MCI. It will address needs for primary, secondary or tertiary prevention.
Assuming that the DORIAN GRAY intervention will lead to a 5-10% reduction in the prevalence of dementia risk factors— such as diabetes, hypertension, obesity, physical inactivity, depression, smoking and low educational attainment— the projected impact in the EU countries by 2050 is estimated to be 1–2 million fewer cases of dementia. Specifically, a 5% reduction in risk factor prevalence would result in 1 million fewer cases, while a 10% reduction would prevent 2 million cases.
