Association of protein-based indices with brain volume and cognition in the Baltimore Longitudinal Study of Aging (BLSA)
Gulzar Daya1, Heather Dark1, Michael Duggan1, Zhongsheng Peng1, Ann Zenobia Moore2, Toshiko Tanaka2, Julián Candia2, Keenan Walker1
11Multimodal Imaging of Neurodegenerative Disease (MIND) Unit, 2Longitudinal Studies Section (LSS), National Institutes of Aging
Objective:
Determine whether proteomic indicators of peripheral (non-neurologic) health are associated with change in cognition and brain volume.
Background:
Numerous peripheral diseases have been associated with brain health. Changes in the plasma proteome related to physical health and disease status likely contribute to cognitive and structural brain changes. Plasma proteomic changes may therefore be leveraged to study the link between peripheral health and brain health.
Design/Methods:
We used plasma samples from participants of the Baltimore Longitudinal Study of Aging (BLSA) to assess 7000+ proteins using SomaScan assay. Brain health was assessed using in BLSA participants with concurrent 3T brain MR imaging to assess total brain volume (TBV). Using SomaLogic’s SomaSignal Test (SST) algorithm, we generated protein-based measures of cardiovascular risk, kidney disease, resting energy rate, body composition, and other health indicators. Linear mixed effects models were used to examine the relationship between SST protein-based health indicators and longitudinal change in TBV and memory.
Results:
The analysis included 1220 participants (mean age: 68.1 [14.3 SD]; 99% cognitively normal).We evaluated 14 unique protein-based health indices (SSTs). None were associated with longitudinal brain volume loss. At baseline, the protein-based indicator of liver fat was associated with better memory. Protein-based indicators of lower V02 max and kidney disease risk were associated with longitudinal declines in memory.
Conclusions:
Protein-based health indicators can be used to understand how facets of peripheral health and disease risk influence brain health in cognitively healthy older adults. Our findings implicate cardiovascular, pulmonary, and kidney health in brain structure or function.