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-ß, 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.