Neural asymmetry during memory encoding and its association with markers of preclinical Alzheimers Disease

BackgroundAlzheimers Disease (AD) is the most common form of dementia and is characterized by cognitive dysfunction that impacts daily functioning. Beta-amyloid (A{beta}) is a cytotoxic protein that deposits in the brain many years prior to the onset of cognitive dysfunction. The preclinical period is a stage of AD in which significant pathology is present without clinical symptoms. A{beta} has been shown to deposit asymmetrically early in the AD trajectory, which has shown to have functional consequences (e.g., asymmetric hypometabolism). We aimed to investigate whether markers of AD and cognitive function were correlated with neural activation asymmetry during memory encoding tasks. MethodsWe recruited participants who were cognitively normal to undergo functional magnetic resonance imaging (fMRI), positron emission tomography (PET) imaging, and cognitive testing. We conducted analyses to identify regions of significant activation during a well-established face-name pair memory encoding task, and to identify regions of significant asymmetry. We then computed hemispheric asymmetry (negative/positive values indicate left/right asymmetry, respectively) and absolute asymmetry (greater values indicate greater asymmetry in either hemisphere) and investigated their associations with age, sex, education, global cerebral amyloid, global cerebral metabolism, memory encoding task performance, white matter hyperintensities, and multiple domains of cognitive function. ResultsWe identified expected regions of significant activation, including the hippocampus, and identified four regions with significant left-hemisphere asymmetry: superior medial frontal gyrus, middle frontal gyrus, supplemental motor area, and medial orbitofrontal gyrus, and two regions with significant right hemisphere asymmetry: putamen and ventral posterolateral nucleus of the thalamus. We found that greater left-hemisphere asymmetry in the middle frontal gyrus was correlated with greater global cerebral glucose metabolism. We also found that better performance in memory, learning, and executive attention was associated with greater absolute symmetry in the thalamus, while better visuospatial performance was associated with greater putamen absolute symmetry. DiscussionFunctional asymmetry is correlated with functional markers (e.g., glucose metabolism) in older cognitively normal adults and may reflect metabolic and cognitive changes. Longitudinal studies may help us better understand these associations and the causal impact of neural activation asymmetry.