Mild behavioral impairment is associated with progression to Alzheimer's disease: A clinicopathological study

Abstract

Introduction: Mild behavioral impairment (MBI) is characterized by later-life emergence of neuropsychiatric symptoms. Investigating its relationship with progression to Alzheimer's disease (AD) would provide insight on its importance as a predictor of AD.

Methods: Cognitively normal participants (N = 11,372) from the National Alzheimer's Coordinating Center were stratified by MBI status, using the Neuropsychiatric Inventory-Questionnaire. We investigated whether MBI and its domains were predictors of progression to clinically-diagnosed AD. MBI as a predictor of progression to neuropathology-confirmed AD was also investigated in those with neuropathological data.

Results: Six percent (N = 671) of participants progressed to AD. MBI (N = 2765) was a significant predictor of progression to clinically-diagnosed (hazard ratio [HR] = 1.75) and neuropathology-confirmed AD (HR = 1.59). MBI domains were also associated with clinically-diagnosed AD, with psychosis having the greatest effect (HR = 6.49).

Discussion: These findings support the biological underpinnings of MBI, emphasizing the importance of later life behavioral changes in dementia detection and prognostication.

Keywords: Alzheimer's disease; mild behavioral impairment; neuropathology; neuropsychiatric symptoms.

Figure 1:

Survival curve to progression of AD based on presence or absence of MBI.

Figure 2:

Hazard ratios and 95% CIs for progression to AD for each MBI domain, after adjusting for covariates. MBI-1: Decreased Drive/Motivation HR=1.77, 95%CI: 1.47–2.14, Wald X2=35.22, p=.001(N=59 (14%) of MBI-1 progressed to AD) MBI-2: Emotional Dysregulation HR=1.35, 95% CI: 1.18–1.54, Wald X2: 18.45, p<.001 (N=144 (8%) of MBI-2 progressed to AD) MBI-3 Impulse Dyscontrol HR=2.01, 95% CI 1.75–2.32, Wald X2: 97.07, p<.001 (N=124 (9%) of MBI-3 progressed to AD) MBI-4: Social Inappropriateness HR=2.25, 95% CI: 1.67–3.03, Wald X2: 28.60, p<.001 (N=25 (11%) of MBI-4 progressed to AD) MBI-5: Psychosis HR=6.49, 95% CI: 4.51–9.34, Wald X2: 101.47, p<.001. (N=14 (17%) of MBI-5 progressed to AD)