The role of loneliness in cognitive decline and risk for dementia

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PROJECT SUMMARY/ABSTRACT Loneliness is highly prevalent among older adults and is associated with substantially increased risk for dementia, particularly Alzheimer’s disease (AD). Recent evidence indicates that loneliness is associated with accelerated rates of cognitive decline and neurobiological changes including accumulation of AD neuropathology, neurodegeneration, and lower levels of brain-derived neurotrophic factor (BDNF). However, most prior studies have relied on cross-sectional designs or assessment of loneliness at a single timepoint, and thus are not able to examine the temporal ordering or directionality of relationships. As a consequence, it remains unclear whether loneliness is a risk factor for, or an indicator of, cognitive and neurobiological changes that are associated with dementia. In the proposed project we will address this critical gap by: examining the longitudinal bidirectional relationships between loneliness and cognitive function (Aim 1), and exploring neurobiological mechanisms linking loneliness with dementia risk (Aim 2). To address these aims, we will leverage intensive longitudinal data and biological samples from the established Einstein Aging Study (EAS), which includes a diverse sample of older adults (aged ≥70 years) recruited via systematic probability sampling from the Bronx County Registered Voter list. These participants have completed up to 4 annual assessment waves that include a 16-day ecological momentary assessment (EMA) burst, collection of blood samples, and in-clinic assessment for mild cognitive impairment (MCI). Blood samples from each assessment have been analyzed for biomarkers of AD neuropathology (amyloid-β, tau), neurodegeneration (neurofilament light [NfL]), and BDNF Val66Met genetic polymorphism. The proposed project will add to this by analyzing BDNF levels in plasma from each assessment wave. The outcomes of the project will be significant in informing whether loneliness is a sensitive early indicator of cognitive dysfunction or a viable target for intervention to reduce risk for cognitive decline and dementia. This will be the first study to examine the longitudinal relationships of loneliness and biomarkers of AD, neurodegeneration, and BDNF in humans, to identify neurobiological mechanisms contributing to increased cognitive decline and dementia risk of lonely individuals.