Effects of race, baseline cognition, and APOE on the association of affective dysregulation with incident dementia: A longitudinal study of dementia-free older adults

Background: Affective symptoms are dementia risk factors. Mild behavioral impairment (MBI) is a neuro-behavioral syndrome that refines incorporation of psychiatric symptomatology into dementia prognostication by stipulating symptoms must emerge de novo in later life and persist for >= 6 months. Here, we investigated the longitudinal association of MBI-affective dysregulation with incident dementia. Methods: National Alzheimer Coordinating Centre participants with normal cognition (NC) or mild cognitive impairment (MCI) were included. MBI-affective dysregulation was operationalized as Neuropsychiatric In-ventory Questionnaire-measured depression, anxiety, and elation at two consecutive visits. Comparators had no neuropsychiatric symptoms (no NPS) in advance of dementia. Cox proportional hazard models were imple-mented to assess the risk of dementia, adjusted for age, sex, years of education, race, cognitive diagnosis, and APOE-epsilon 4 status, with interaction terms as appropriate. Results: The final sample included 3698 no-NPS (age:72.8; 62.7 % female), and 1286 MBI-affective dysregulation participants (age:75; 54.5 % female). MBI-affective dysregulation had lower dementia-free survival (p < 0.0001) and greater incidence of dementia (HR = 1.76, CI:1.48-2.08, p < 0.001) versus no NPS. Interaction analyses revealed that MBI-affective dysregulation was associated with higher dementia incidence in Black participants than White (HR = 1.70, CI:1.00-2.87, p = 0.046), NC than MCI (HR = 1.73, CI:1.21-2.48, p = 0.0028), and APOE-epsilon 4 noncarriers than carriers (HR = 1.47, CI:1.06-2.02, p = 0.0195). Of MBI-affective dysregulation con-verters to dementia, 85.5 % developed Alzheimer's disease, which increased to 91.4 % in those with amnestic MCI. Limitations: MBI-affective dysregulation was not stratified by symptom to further examine dementia risk. Conclusions: Emergent and persistent affective dysregulation in dementia-free older adults is associated with substantial risk for dementia and should be considered in clinical assessments.