Sex Moderates the Association between Frailty and Mild Behavioral Impairment

Background Frailty has been associated with cognitive markers of dementia but its relationship with behavioral markers of dementia are poorly understood. Objectives To investigate the association between frailty and mild behavioral impairment (MBI), and whether this association is moderated by sex. Design Cross-sectional observational study. Participants/Setting 219 non-dementia participants (cognitively normal and mild cognitive impairment) from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study. Measurements Frailty was measured using the frailty index (FI) with higher scores indicating more health deficits/greater frailty. MBI symptoms were derived from Neuropsychiatric Inventory Questionnaire scores using a published algorithm with a cut-off of >0 indicating MBI symptom presence and higher scores indicating greater severity. Multivariable logistic and linear regressions adjusted for age, sex, education, and cognitive diagnosis were used to test the association between FI and MBI symptom presence and severity, respectively, with MBI as the outcome variable. An FI-by-sex interaction term was included to test for sex-dependent effects. Results The FI mean and SD across the entire cohort was 0.14 +/- 0.06 (median = 0.14, IQR = 0.09-0.17, range = 0.02-0.38). Higher FI scores were associated with the presence of MBI symptoms both globally and in the domains of decreased motivation, affective dysregulation, and psychosis. Higher FI scores were also associated with more severe MBI symptoms in a sex-dependent manner: both sexes reported similarly low MBI symptom severity at low (-1 SD) levels of FI but males reported 1.9x higher MBI symptom severity relative to females at high (+1 SD) levels of FI. Conclusions The FI is associated with both the presence and severity of MBI, especially for males. This suggests that screening for early dementia risk should incorporate assessments of MBI for patients with frailty, and assessments of frailty for patients with MBI.