Measuring loneliness at a national scale: The measuring loneliness in England (INTERACT) study's approach and initial findings.

Dementia is a devastating neurological syndrome characterized by progressive cognitive decline, memory loss and behavioral changes. Dementia remains one of the significant health challenges that affects millions of people worldwide and is projected to grow significantly due to aging populations [, ]. It is a major cause of disability among older adults and is associated with significant socio-economic burden with higher cost of health care and long-term care for dementia patients []. The most common cause of dementia is Alzheimer’s disease that accounts for over 60% of dementia cases. Other cases of dementia include vascular dementia, Lewy body dementia and frontotemporal lobar dementia [, ]. Currently, there is no cure for dementia. Dementia is a multifactorial syndrome involving several risk factors including aging, life style, environmental factors, comorbidities and genetics []. Although the precise mechanisms underlying the onset of dementia are not yet clear, inflammation has emerged as one of the central processes underlying its pathogenesis [–]. Inflammation is a defensive process crucial for host defense against injury and infection as well as homeostasis maintenance. However, dysregulated inflammation can be detrimental to health. In the brain, persistent activation of microglia and astrocytes triggers the release of pro-inflammatory cytokines, which can cause neuronal injury and synaptic dysfunction [, , ]. This sustained neuroinflammatory response not only accelerates amyloid deposition and tau hyperphosphorylation but also interferes with neuronal repair and neurogenesis [–]. In addition, systemic inflammation, such as microbial infections or chronic systemic conditions like obesity and diabetes have been associated with increased levels of circulating cytokines that can exacerbate neurodegenerative processes by altering the permeability of blood–brain barrier and allowing bidirectional crosstalk between peripheral and central nervous system [–]. Collectively, these studies suggest inflammation as a potentially modifiable risk factor for neurodegeneration.