Investigating the impact of loneliness on brain aging and pre-symptomatic Alzheimer's disease progression

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R01AG068563 Administrative Supplement (PI: Spreng R.N.) PROJECT SUMMARY. Feelings of loneliness in later life are associated with poor health outcomes including loss of cognitive ability, greater dementia risk, and higher mortality rates. Yet surprisingly little is known about how loneliness impacts the brain in older adulthood. Loneliness may be an antecedent or accelerant, promoting the advance of neuropathological changes and increasing dementia risk. The goal of the parent grant is to investigate the relationship between loneliness and brain structure and function in typical aging and in individuals at risk for AD. We are examining these associations in a large population dataset (UK Biobank, parent grant AIM 1) as well as in a local, longitudinally followed cohort of older adults at elevated risk for AD (parent grant AIM 2). However, pandemic-related social distancing restrictions were imposed between the two longitudinal datapoints for the parent grant, complicating our proposed analysis plan for AIM 2. We know that loneliness among older adults increased significantly during the pandemic. As these acute impacts of the pandemic are wholly coincident with our longitudinal study design, it is now challenging to isolate these from our originally hypothesized associations between loneliness and presymptomatic AD progression over time. The goal of the administrative supplement is to leverage the data collection infrastructure in place for the parent grant to collect an additional time point of data in this cohort. This will provide two post-pandemic timepoints of brain, behavior and loneliness data (Supplementary Aim 1), enabling us to model and isolate the acute and more chronic impacts of the pandemic from normal, longitudinal changes originally predicted in the parent grant. In addition, we will take advantage of recent innovations in plasma-based biomarkers of AD pathology to derive novel markers of AD- risk in our cohort (Supplementary Aim 2). Importantly, these markers of AD risk will be temporally aligned with proposed brain and behavioral data collection in Supplementary Aim 1. As described in the parent grant AIM 2, this program of research will advance our understanding of how loneliness interacts with brain structure and function in pre-symptomatic AD. The Administrative Supplement is critically necessary to achieve this goal, enabling us to measure, model and characterize the acute, and hopefully exceptional, impacts of the pandemic from normally occurring age- and disease-related changes that were the central focus of the parent grant. 1