Intraindividual Variability as a Correlate of White Matter Decline

Aging and early-stage Alzheimer disease (AD) have been associated with increased reaction time intraindividual variability (IIV). In previous studies this age-related increase in IIV has been associated with white matter volumes and microstructure. However, the association between IIV and white matter has not been contextualized with other aspects of cognitive performance and neuroanatomical structure, in particular with median reaction time and estimates of gray matter. Using cognitive composites derived from three attentional tasks (Stroop, Simon, and CVOE switching), in conjunction with estimates of regional gray matter thickness and white matter volume, the present dissertation examined two aims on a group of cognitively normal and early-stage AD participants. Based on previous literature, the first aim examined evidence for a double dissociation between aspects of cognitive performance and neuroanatomical structure, such that the coefficient of variation (CoV, a measure of IIV) would uniquely be associated with white matter while median RT associated with gray matter thickness. The second aim examined evidence for a mediational role of CoV, such that this variable accounted for the association observed between regional white matter and performance on working memory and episodic memory tasks. Furthermore, Aim 2 examined whether CoV mediated the relationship between two genetic factors (Apolipoprotein and catechol-O-methyltransferase) and memory performance as well. No support was found for either aim. Discussion focuses on possible explanations for the lack of reliable associations. Based on observations from post-hoc analyses it is suggested that group differences (e.g., cognitively normal vs. early-stage AD) in the sensitivity of IIV to cognitive performance and white matter may be a factor in the association of IIV with neurocognitive measures