The role of Mild Behavioral Impairment in a future era of Alzheimer’s disease modifying treatments

Abstract

Early clinical risk markers of neurodegenerative diseases, such as Alzheimer’s disease (AD), can be considered fundamental in a new era with novel disease modifying treatments on the horizon. Mild Behavioral Impairment (MBI) is a diagnostic construct defined by the later-life emergence of persistent neuropsychiatric symptoms (e.g. apathy, anxiety, depression, amongst others) displayed by older adults, with the aim to identify individuals at increased risk of future dementia. According to established MBI criteria the syndrome can co-occur with mild cognitive impairment due to a neurodegenerative disease or even precede it, and in fact, MBI is most meaningful when reported in conjunction with cognitive status, as MBI-associated risk is moderated by cognitive status. MBI symptomatology has been reported prevalent among older adults, as well as in patients with early stages of neurodegenerative disease. Symptoms of MBI are further associated with several clinically negative outcomes, such as a reduced quality of life, increased caregiver burden and earlier institutionalization. In support of the MBI construct, several previous reports have demonstrated MBI to be predictive of future cognitive decline, dementia, or AD. The construct is also related to AD biomarkers including beta-amyloid, tau, and cerebral atrophy. Intriguingly, an earlier study indicates that MBI even can precede memory deficits in its association with early tau deposition in cognitively unimpaired elderly with confirmed amyloid-beta pathology, strengthening its position as an early marker of dementing biochemical processes. Despite this growing evidence of being both prevalent and an early prognostic marker, MBI is still only given diminutive consideration in contemporary clinical diagnostic criteria for AD. Perhaps so since the added value of MBI in such criteria has rarely been investigated. Consequently, cognitively unimpaired subjects with positive MBI and AD biomarker status face the risk of not being eligible for a future disease modifying AD treatment since they formally do not fulfill AD diagnostic criteria. Hence, studies exploring the added value of MBI in clinical diagnostic criteria for neurocognitive disorders are prompted.