Clinical Manifestations.

Abstract

Impulse dyscontrol, i.e., excessive motor activity and/or physical and verbal aggression is common in dementia. However, impulse dyscontrol can also emerge in advance of dementia, but is often normalized due to age, or framed as a psychiatric condition. Thus, the association between these symptoms and incident dementia is unclear. Mild behavioral impairment (MBI) leverages risk associated with later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a high-risk group for incident dementia. Impulse dyscontrol is one of five MBI domains. Here, in dementia-free participants, we assessed risk of progression to dementia in MBI-impulse dyscontrol and conventionally-measured impulse dyscontrol symptoms (Conv-ID). Dementia-free National Alzheimer Coordinating Centre participants were included. Neuropsychiatric Inventory Questionnaire irritability, agitation, and aberrant motor behavior items were used to identify impulse dyscontrol. MBI-impulse dyscontrol was operationalized by symptom presence at more than two-thirds of pre-dementia study visits (symptom persistence criterion) in those with no history of psychiatric disorders (symptom emergence criterion). Conv-ID required symptoms only at baseline without consideration of past psychiatric history. Kaplan-Meier survival curves and Cox proportional hazards models, adjusted for age, sex, education, race, and APOE-e4 status, were generated to compare survival probability and dementia incidence rates of MBI-impulse dyscontrol and Conv-ID to No-NPS. The sample comprised 1,884 MBI-impulse dyscontrol (age = 74.5±9.7; 40.9% female), 3,676 Conv-ID (age = 71.0±9.4; 47.0% female), and 6,362 No-NPS participants (age = 71.0±10.3; 64.7% female) (Table 1). MBI-impulse dyscontrol had lower dementia-free survival (p<0.0001) and 2.23-fold greater dementia incidence compared to No-NPS (CI:1.99-2.50, p<0.001, Figure 1(A)); Conv-ID had lower dementia-free survival (p<0.0001) and 1.39-fold greater dementia incidence compared to No-NPS (CI:1.25-1.54, p<0.001, Figure 1(B)). Compared with a conventional approach to assess agitated and impulsive behaviors, MBI-impulse dyscontrol was associated with greater dementia incidence. Applying the MBI criteria of later-life emergence and persistence of symptoms provides a more specific approach to identify those at risk for incident dementia, who might otherwise be dismissed due to normalization of these behaviors in older persons or labelled with a psychiatric condition. This approach may allow for earlier implementation of preventative measures, pharmacological and non-pharmacological, improving outcomes and quality of life for patients and their caregivers.