Brain free‐water increases in mild behavioral impairment

Abstract

AbstractBackgroundMild behavioural impairment (MBI) is proposed as a diagnostic construct to identify dementia‐free individuals with sustained neuropsychiatric symptoms as an early manifestation of dementia. Our previous study has demonstrated that MBI predicts faster cognitive decline and progression to dementia. Other studies have shown that MBI was associated with Alzheimer’s disease biomarkers for Aβ and tau. However, cerebrovascular disease (CeVD), which is another critical pathology in dementia, has not been investigated in MBI. Here, we sought to test brain free‐water (FW) alterations, a marker for CeVD, in MBI compared with non‐MBI participants and their associations with longitudinal changes in cognition, function, and neuropsychiatric symptoms.MethodLongitudinal global cognitive scores, clinical dementia rating sum‐of‐boxes (CDR‐SoB), neuropsychiatric inventory (NPI) scores, over 5 years were reported in 281 dementia‐free participants (40 MBI and 241 non‐MBI). MBI was diagnosed using established criteria. All participants underwent T1‐weighted structural and diffusion MRI at baseline. FW imaging method was applied to derive individual‐level white matter (WM) and grey matter (GM) FW maps from diffusion MRI. We compared baseline GM‐FW and WM‐FW between non‐MBI and MBI subjects. We then tested the associations of MBI‐related FW increase with baseline and longitudinal changes in global cognition, CDR‐SB, and NPI scores using linear regression models.ResultMBI had greater GM‐FW in executive control (prefrontal), motor sensory (precentral), attention (insula) and memory (left temporal and right cingulate and cuneus) networks and widespread higher WM‐FW compared with non‐MBI (Fig‐1). Both higher GM‐FW and WM‐FW were associated with lower global cognition, higher CDR‐SB, and higher NPI scores across all participants at baseline (Table‐1). There was no interaction effect of MBI status on such association. Moreover, higher baseline GM‐FW and WM‐FW were associated with longitudinal worsening in global cognition, CDR‐SB, and NPI scores (Table‐2). Interestingly, such associations were greater in MBI than in non‐MBI (Fig‐2).ConclusionThis study demonstrated that MBI was associated with increased brain FW, which may have contributed to the relationship between persistent neuropsychiatric disturbances and clinical and cognitive outcomes. Early detection of cerebrovascular‐related FW alteration may allow for timely management of MBI individuals before development of dementia.