The Healthy Brain Aging Lab studies changes in brain structure and function across the human lifespan, with particular emphasis on vascular and metabolic health factors and lifestyle behaviors that shape aging trajectories. Studies typically recruit community-dwelling adults of all ages to complete diverse cognitive testing, MRI, and bloodwork with the intent of multiple assessments over several years. In this manner, we evaluate and quantify individual differences as a means to study the organization of human cognition, its relation to the brain, and mechanism of their decline over long periods.

 

Contributions of Metabolic Dysfunction and Oxidative Stress to Cognitive Decline

Daugherty developed the Free-Radical Induced Energetic and Neural Decline in Senescence (FRIENDS) model of aging and disease (Raz & Daugherty, 2018). On-going studies in the lab evaluate the promises and limitations of brain iron accumulation, measured from non-invasive MRI, as a biomarker of future decline in brain structure and function. Brain iron accumulation is a proxy indicator of oxidative stress and metabolic dysfunction, which we use in observational studies to examine interactions with cardiovascular health, such as hypertension, metabolic syndrome and inflammation. We also consider possible protection from frequent aerobic exercise and high cardiorespiratory fitness. In multivariate analysis we use these multiple factors to examine correlations with longitudinal decline in brain structure and cognitive function.

Vulnerability of the Hippocampus and Dependent Memory Function

The hippocampus is superbly vulnerable to the effects of aging and decline in the structure is associated with typical decline in memory function, with even greater decline seen in disease such as mild cognitive impairment and Alzheimer’s disease. The hippocampus is a complex structure that is composed of several distinct regions, or subfields, which are defined by unique microstructure and function. With state-of-the-art protocols we can visualize the hippocampal subfields on MRI and use highly-reliable manual segmentation to extract volumes. On-going studies aim to understand differential aging trajectories of each region, their selective sensitivity to cardiovascular health risk and specific cognitive correlates. With additional collaborations, we extend this to evaluate lifespan development from childhood to late adulthood, as well as risk associated with late-life dementia. Dr. Daugherty serves on the leadership committee of the Hippocampal Subfield Segmentation Group—an international collaboration of over 200 researchers from 15 countries that is dedicated to the development, validation and dissemination of a harmonized protocol to segment medial temporal lobe regions on MRI.

Neural and Cognitive Correlates of Human Spatial Navigation Skill

Higher-order cognitive abilities are defined by the combined action of multiple neural cognitive systems—human spatial navigation is one example of this. Spatial navigation ability is necessary for independent, daily living and is vulnerable to declines in aging and related disease. We study human spatial navigation ability in a virtual adaptation of the Morris water maze and quantify navigation paths for efficiency and complexity. On-going studies aim to understand the contributions of different cognitive functions—e.g., episodic memory, working memory and procedural skill—and their neural correlates to successful human navigation, and specific correlates of age-related decline. With longitudinal study we can not only address questions about learning and immediate memory, but also long-term retention and adaptation.