AbstractBackgroundNeuropsychiatric symptoms (NPS) are risk factors for dementia. Mild behavioral impairment (MBI) is a neurobehavioral syndrome that refines NPS assessment to improve dementia prognostication by identifying later‐life emergent and persistent NPS specifically as the at‐risk group. Affective dysregulation contributes to dementia risk and is an MBI domain characterized by the inability to regulate emotions. Here, we investigate the longitudinal association of MBI‐affective dysregulation with incident dementia in dementia‐free older adults from the National Alzheimer Coordinating Centre (NACC).MethodNACC participants with no history of psychiatric, neurological, or neurodevelopmental disorders were included. MBI‐affective dysregulation status was determined based on Neuropsychiatric Inventory Questionnaire (NPI‐Q) depression, anxiety, and elation scores at two consecutive visits. The comparator group involved participants with no NPS prior to dementia. Participants with dementia at baseline were excluded from the study. Kaplan‐Meier curves of dementia‐free survival over ten years were generated for MBI‐affective dysregulation versus no NPS. Cox proportional hazard models were implemented to assess the risk of dementia, adjusted for age, sex, years of education, race, APOE e4 status, and clinical cognitive diagnosis. Potential interactions were further explored for relevant model covariates.ResultThe final sample consisted of 3,446 participants with no NPS (mean age 73.1; 63.0% female), and 1,156 with MBI‐affective dysregulation (mean age 75.1; 53.9% female). MBI‐affective dysregulation was associated with lower chance of dementia‐free survival (log rank, p<0.001) and 1.67 times greater risk of dementia compared to no NPS (CI:1.4‐2, p<0.001). Moderation analysis revealed that in participants with normal cognition (NC), those with MBI‐affective dysregulation were at 2.56 times greater risk of dementia than those with no NPS (CI:1.87‐3.49, p<0.001). In mild cognitive impairment (MCI), the risk associated with MBI‐affective dysregulation was 1.4 times greater than no NPS (CI:1.14‐1.72, p = 0.02).ConclusionThe emergence of persistent affective dysregulation symptoms in dementia‐free older adults is associated with substantial risk for dementia. When emerging in individuals with NC, these persistent affective symptoms represent a greater risk compared to those with no NPS, compared to emergence of these symptoms in MCI. MBI‐affective dysregulation is an important risk factor for dementia and should be considered in clinical assessments.