Mild behavioral impairment is associated with sleep apnea, insomnia and brain white matter hyperintensity burden

Background Mild behavioral impairment (MBI) is a neurobehavioral syndrome associated with increased risk for Alzheimer’s disease (AD) and other neurodegenerative disorders. White matter hyperintensities (WMH) are brain lesions associated with cerebrovascular insult and contribute to cognitive decline across the cognitive spectrum (normal cognition, mild cognitive impairment (MCI) and dementia). Sleep disturbance is common among older adults with cognitive impairment and like MBI, is a modifiable AD risk factor that can affect brain structure including WMH. We sought to examine the prevalence of MBI and its relationship with sleep and WMH in a community cohort of older adults. Method Participants enrolled in the Wake Forest AD Research Center (ADRC) Clinical Core cohort (N = 633, mean age = 70.4 years) provided history of sleep apnea and insomnia, underwent neuropsychological assessment and neuropsychiatric symptom assessment, as reported by an informant on the Neuropsychiatric Inventory Questionnaire (NPI‐Q). MBI scores were derived from the NPI‐Q severity and included 10 symptoms reflecting affective dysregulation, impulse control, decreased motivation, social inappropriateness and abnormal perception or thought content, and excluded NPI‐Q questions on sleep and appetite. T1 and T2 FLAIR MRI were obtained; T1 and FLAIR were segmented to quantify WMH volume, which was scaled by head size and log transformed. Global cognitive status was assessed using the clinical dementia rating (CDR) global score. Result In our sample, 24% of participants had MBI. Normal cognition (CDR = 0) participants had significantly lower rates of MBI compared to both MCI (CDR = 0.5) and dementia (CDR ≥ 1, Figure 1, p<.001). MBI scores were also significantly higher in participants with than without sleep apnea (Fig. 2, p = 0.003) and insomnia (Figure 3, p = 0.043). Further, WMH volume was higher in participants with MBI (Figure 4, p<.001). Conclusion MBI increased in prevalence with cognitive impairment. Sleep disturbances and greater WMH burden in our MBI participants may increase their risk of cognitive decline for normal cognition and MCI groups and relate to poor behavioral and health outcomes in participants with dementia. Future studies will assess interactions of sleep, MBI and WMH across cognitive groups and their association with risk of conversion to MCI or AD.