Sex as a moderator of the association between frailty and mild behavioral impairment

Abstract Background Frailty and mild behavioral impairment (MBI) are associated with dementia and sex differences are recognized in both. Each can facilitate early detection and treatment. This study investigated the association between frailty and MBI and whether this association is moderated by sex. Method Cross‐sectional data from 219 participants (48.9% female; mean and SD of age = 72.2 ± 6.5 years, and education = 15.8 ± 3.5 years) from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS‐ND) study was analyzed. No participants had dementia: 58 (26.5%) were cognitively normal and 161 (73.5%) had mild cognitive impairment. Frailty was measured using the frailty index (FI); higher scores indicate 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. As with the FI, greater MBI severity was indicated by higher scores. 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 in the linear regression model to test for sex‐dependent effects. Result 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). Approximately half (51.6%) showed MBI symptoms (mean and SD of severity = 1.8 ± 2.7). Higher FI scores were associated with the presence of MBI symptoms both globally and in the domains of decreased motivation, affective dysregulation, and psychosis (Table 1). 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 (Figure 1). Conclusion The FI is associated with both the presence and severity of MBI, especially for males. These findings suggest that patients with frailty should be assessed for MBI and that patients with MBI should be assessed for frailty.