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

Affective symptoms are dementia risk factors. Mild behavioral impairment (MBI) is a neurobehavioral 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.National Alzheimer Coordinating Centre participants with normal cognition (NC) or mild cognitive impairment (MCI) were included. MBI-affective dysregulation was operationalized as Neuropsychiatric Inventory 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 implemented to assess the risk of dementia, adjusted for age, sex, years of education, race, cognitive diagnosis, and APOE-ε4 status, with interaction terms as appropriate.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-ε4 noncarriers than carriers (HR = 1.47, CI:1.06-2.02, p = 0.0195). Of MBI-affective dysregulation converters to dementia, 85.5 % developed Alzheimer's disease, which increased to 91.4 % in those with amnestic MCI.MBI-affective dysregulation was not stratified by symptom to further examine dementia risk.Emergent and persistent affective dysregulation in dementia-free older adults is associated with substantial risk for dementia and should be considered in clinical assessments.