Linking the neural signature of response time variability to Alzheimer's disease pathology and cognitive functioning

Promising evidence has suggested potential links between mind-wandering and Alzheimer's disease (AD). Yet, older adults with diagnosable neurocognitive disorders show reduced meta-awareness, thus questioning the validity of probe-assessed mind-wandering in older adults. In prior work, we employed response time variability as an objective, albeit indirect, marker of mind-wandering to identify patterns of functional connectivity that predicted mind-wandering. In the current study, we evaluated the association of this connectome-based, mind-wandering model with cerebral spinal fluid (CSF) p-tau/Aβ ₄₂ ratio in 289 older adults from the Alzheimer's Disease NeuroImaging Initiative (ADNI). Moreover, we examined if this model was similarly associated with individual differences in composite measures of global cognition, episodic memory, and executive functioning. Edges from the high response time variability model were significantly associated with CSF p-tau/Aβ ratio. Furthermore, connectivity strength within edges associated with high response time variability was negatively associated with global cognition and episodic memory functioning. This study provides the first empirical support for a link between an objective neuromarker of mind-wandering and AD pathophysiology. Given the observed association between mind-wandering and cognitive functioning in older adults, interventions targeted at reducing mind-wandering, particularly before the onset of AD pathogenesis, may make a significant contribution to the prevention of AD-related cognitive decline.