Brain-behavior investigation of potential cognitive markers of Alzheimer’s disease in middle age: a multi-modal imaging study

Early detection of Alzheimer’s disease remains a challenge, and the development and validation of novel cognitive markers of Alzheimer’s disease is critical to earlier disease detection. The goal of the present study is to examine brain-behavior relationships of translational cognitive paradigms dependent on the medial temporal lobes and prefrontal cortices, regions that are first to undergo Alzheimer’s-associated changes. We employed multi-modal structural and functional MRI to examine brain-behavior relationships in a healthy, middle-aged sample (N = 133; 40–60 years). Participants completed two medial temporal lobe-dependent tasks (virtual Morris Water Task and Transverse Patterning Discriminations Task), and a prefrontal cortex-dependent task (Reversal Learning Task). No associations were found between various MRI measures of brain integrity and the Transverse Patterning or Reversal Learning tasks ( p ’s > .05). We report associations between virtual Morris Water Task performance and medial temporal lobe volume, hippocampal microstructural organization, fornix integrity, and functional connectivity within the executive control and frontoparietal control resting state networks (all p’s < 0.05; did not survive correction for multiple comparisons). This study suggests that virtual Morris Water Task performance is associated with medial temporal lobe integrity in middle age, a critical window for detection and prevention of Alzheimer’s disease, and may be useful as an early cognitive marker of Alzheimer’s disease risk.