Mild Behavioral Impairment as a Marker of Cognitive Decline in Cognitively Normal Older Adults

This is the author accepted manuscript. the final version is available from Elsevier via the DOI in this recordObjective: Mild Behavioral Impairment (MBI) is a neurobehavioural syndrome characterized by later life emergent neuropsychiatric symptoms (NPS) which represent an at-risk state for incident cognitive decline and dementia in people with Mild Cognitive Impairment. We undertook a study to determine whether MBI was associated with progressive changes in neuropsychological performance in people without significant cognitive impairment. Methods: 9,931 older adults enrolled in the PROTECT study who did not have MCI or dementia undertook a comprehensive neuropsychological battery measuring attention, reasoning, executive function and working memory at baseline and one year. MBI was ascertained using self-administration of the MBI-C at one year, and participants grouped according to MBI status: no symptoms, intermediate neuropsychiatric symptoms and MBI. All assessments were completed online and data analyzed using MMRM ANOVA. Results: 949 (10%) people had MBI. These individuals had significantly worse cognitive performance at baseline and significantly greater decline over one year in the four composites cognitive scores measuring attentional intensity (F(2,8578)=3.97,p=0.019), sustained attention (F(2,8578)=18.63, p<.0001), attentional fluctuation (F(2,8578)=10.13, p=<.0001) and working memory F(2,9895)=13.1, p<.0001. Conclusions: Our novel findings show that MBI is associated with faster decline in attention and working memory in this cognitively normal sample. MBI may be an earlier marker of neurodegenerative disease than MCI, captured at the stage of SCD or before, raising the possibility that MBI represents a novel target for dementia clinical trials or prevention strategies.National Institute for Health Research (NIHR