Predicting continuous amyloid PET levels with CSF and plasma brain-derived p-tau217.

Loneliness is a subjective, distressing experience resulting from a discrepancy between desired and actual social relationships [, ]. It is distinct from social isolation, which refers to an objective lack of social contact []. Loneliness and social isolation are recognised as major global public health challenges, with substantial implications for mental, physical and social wellbeing. Extensive research demonstrated strong associations between loneliness and adverse health outcomes, including depression, anxiety, cognitive decline, cardiovascular disease, hypertension and increased mortality risk [, , –]. Recognising the growing burden, the World Health Organisation (WHO) identified social isolation and loneliness as critical determinants of health, highlighting the need for evidence-based interventions and policy responses [, ]. Beyond individual wellbeing, the economic burden of loneliness is equally profound, contributing to higher healthcare utilisation, lost workplace productivity and increased demand for social care services. In the United Kingdom (UK) [], loneliness costs employers up to £3.7 billion annually or at least £9,976 per person per year [, ]. Loneliness is not confined to older adults as earlier studies identified a life-course distribution, often described as U-shaped, with peaks in adolescence and later life []. Young adults (16–25 years) consistently report high levels of loneliness [], possibly due to academic stress, employment insecurity and increased digital socialisation, which may not always translate into meaningful social bonds [, ]. Meanwhile, in older populations, loneliness is frequently associated with bereavement, declining health and reduced social participation [].