MBI symptoms predict progression to Alzheimer's disease independent of neuropathology.

Abstract

Mild behavioural impairment (MBI), characterized by the emergence of neuropsychiatric symptoms (NPS) in late-life, has been associated with cognitive decline and an increased risk of dementia. We investigated the effect of MBI symptoms and AD neuropathology on the risk of progression to mild cognitive impairment (MCI) and Alzheimer's disease (AD) in cognitively normal (CN) elderly over five years. Participants from the National Alzheimer's Coordinating Center (NACC) neuropathology dataset, with low/intermediate/high AD neuropathologic change (ADNC), who were CN five years prior to death, and who had a diagnosis of CN, MCI, or AD at death were included. Neuropsychiatric Inventory-Questionnaire items were clustered into MBI domains (MBI-1: drive/motivation, MBI-2: emotional regulation, MBI-3: impulse control, MBI-4: social inappropriateness, and MBI-5: psychotic symptoms). Using a multinomial regression, we investigated the effect of ADNC and MBI+ status, and MBI domains, on progression to MCI, and AD, compared to CN stable. Covariates included age, Mini-Mental Status Examination (MMSE) score, and presence of APOE e4 allele. MBI-4 and -5 were not investigated as each group had N=3 and N=1, respectively. Of the 349 participants who met criteria for inclusion (mean±SD age=85±8, 39% male), 55% (N=192) were CN stable, 25% (N=87) progressed to MCI, and 20% (N=70) progressed to AD prior to death. Intermediate/high ADNC predicted progression to MCI (OR: 1.05 95%CI .15-.83, p=.02) and AD (OR: 2.91, 95%CI .01-.22, p<.001). MBI+ status independently predicted progression to AD only (OR: 1.32, 95% CI .10-.70, p=.01). In each MBI domain model, intermediate/high ADNC predicted progression to MCI and AD (all, p<.05). MBI-1 (OR: 2.07, 95% CI .02-.66, p=.01), MBI-2 (OR: 1.06, 95% CI .13-.94, p<.04), and MBI-3 (OR: 1.51, 95% CI .06-.80, p=.02) each independently predicted progression to AD only. In CN individuals, intermediate/high ADNC pathology was significantly associated with progression to MCI and AD up to five years later. However, MBI+ status and MBI domains independently predicted progression to AD, and not MCI. These findings suggest that the effect of MBI symptoms on progression to AD may be independent of AD neuropathology.