Exploring dementia: From molecular mechanisms to clinical manifestations

Dementia is a multifactorial syndrome characterized by progressive functional decline and increasing dependency among older adults. This thesis investigates dementia from multiple perspectives, including motor function, cardiovascular and immune pathways, gut-related metabolites, and genetic regulatory mechanisms, with the overarching goal of identifying opportunities for prevention and intervention.

The first part of this thesis focuses on identifying individuals in the prodromal stages of dementia, including mild cognitive impairment (MCI) and motoric cognitive risk syndrome (MCRS). The findings highlight the importance of combining cognitive and functional markers, such as gait speed, to improve dementia risk stratification. Furthermore, estimates of life expectancy among individuals with MCI provide insight into future care needs and the potential impact of cognitive impairment on patients and their families.

A central focus of this thesis is the relationship between cardiovascular health and neurodegeneration. The studies show that subclinical cardiac dysfunction, even before the onset of overt cardiovascular disease, is associated with adverse brain outcomes. In addition, this thesis explores the role of amyloid pathology beyond the brain. Additional studies investigate circulating biomarkers, including microRNAs and immunoglobulins, highlighting their potential to reveal biological pathways involved in dementia while emphasizing the challenges of translating molecular signals into clinical applications.

Finally, this thesis sheds light on protein misfolding as a shared mechanism across common and rare forms of dementia, including Creutzfeldt-Jakob disease. Together, these findings emphasize that dementia can only be fully understood by considering processes across multiple levels, from molecular mechanisms to population-level determinants.