Cognitive fatigability is an objective performance decrement that occurs over time during a task requiring sustained cognitive effort. Although cognitive fatigability is a common and debilitating symptom in multiple sclerosis (MS), there is currently no standard for its quantification. The objective of this study was to validate the Paced Auditory Serial Addition Test (PASAT) discrete and regression-based normative data for quantifying performance and cognitive fatigability in an Ontario-based sample of individuals with MS. Healthy controls and individuals with MS completed the 3″ and 2″ versions of the PASAT. PASAT performance was measured with total correct, dyad, and percent dyad scores. Cognitive fatigability scores were calculated by comparing performance on the first half (or third) of the task to the last half (or third). The results revealed that the 3″ PASAT was sufficient to detect impaired performance and cognitive fatigability in individuals with MS given the increased difficulty of the 2″ version. In addition, using halves or thirds for calculating cognitive fatigability scores were equally effective methods for detecting impairment. Finally, both the discrete and regression-based norms classified a similar proportion of individuals with MS as having impaired performance and cognitive fatigability. These newly validated discrete and regression-based PASAT norms provide a new tool for clinicians to document statistically significant cognitive fatigability in their patients.

Objectives: Generativity is the desire and actions to improve the well-being of younger generations. Generativity is associated with purpose in life, with both being shown to independently improve cognition in older adults. Our aims were to identify the neural substrates supporting generativity and determine the mechanism underlying the relationship between generativity and purpose in life in older adults. Method: Forty-three older adults (Mage = 70.33, 79.1% female) at risk for Alzheimers disease underwent resting-state functional magnetic resonance imaging and completed questionnaires assessing generativity, social support, and purpose in life. Seed-to-voxel analyses examined if resting-state functional connectivity (rsFC) of the ventromedial prefrontal cortex (vmPFC) and ventral striatum, key nodes at the intersection of subjective valuation and self-transcendence, were associated with generativity. Moderated mediation models examined if social support or rsFC mediated or moderated the association between generativity and purpose in life, respectively. Results: Generative desire was associated with enhanced rsFC between the vmPFC and right dorsolateral prefrontal cortex (rdlPFC). Affectionate social support fully mediated the relationship between generative desire and purpose in life, and rsFC between the vmPFC and rdlPFC significantly moderated this association. Discussion: This study is the first to examine the rsFC underlying generativity and provides mechanistic insight into how purpose in life is enhanced through generative desire. Generative desire is supported by rsFC implicated in value-based social decision making and is associated with purpose in life through enhanced love and affection from others. This knowledge contributes to future developments of personalized interventions that promote resilience in at-risk aging.