White matter hyperintensities and mild behavioral impairment: Findings from the MEMENTO cohort study

Background: White matter hyperintensities (WMH) contribute to cognitive decline and increase risk for dementia. Mild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by the emergence and persistence of neuropsychiatric symptoms (NPS) in later life as an at-risk state for incident cognitive decline and dementia. Both WMH and MBI are common in patients with mild cognitive impairment (MCI), but few studies have established the link between these two risk markers in this population. Methods: Participants were memory clinic patients with MCI from the French MEMENTO study. WMH volume was quantified using brain magnetic resonance imaging. Participants were categorized into MBI+ and MBIstatus based on NPS persistence, and the association between MBI status and domains with WMH volume was assessed with linear regression. Results: A total of 768 participants [mean age 72.8 (SD=8.00); 57% female] were included. MBI (i.e., persistent NPS) was present in 229 participants (29.8%). MBI+ status was significantly associated with lower MMSE score and male sex. Compared to MBI-, MBI+ status was associated with 9.4% higher WMH volume [p = 0.01 (95% CI 2.0% to 16.7%)]. In this model, MMSE score was not associated with WMH volume. None of the MBI domains individually predicted greater WMH volume, although emotional dysregulation, impulse dyscontrol, and apathy trended towards significance. Conclusions: In a memory clinic sample of older adults with MCI, MBI was associated with higher WMH volume. Global MBI status outperformed MMSE and individual MBI domains, supporting the utility of MBI, a multi-NPSdomain composite assessment, for predicting WMH volume.