Mild behavioral impairment is associated with amyloid, tau and neurodegeneration in mild cognitive impairment

Abstract Background Mild behavioural impairment (MBI) is a dementia at‐risk syndrome using later‐life neuropsychiatric symptoms (NPS) to determine risk. For some, MBI may be a non‐cognitive marker of neurodegeneration. A hallmark criterion of MBI is symptom persistence. We examined associations between NPS and Alzheimer’s disease (AD) proteins for amyloid, tau, and neurodegeneration in participants with mild cognitive impairment (MCI), comparing groups with persistent, transient, and no NPS. Method ADNI participant data was used for this study including Neuropsychiatric Inventory (NPI) scores for baseline and one‐year visits and CSF measures for β‐amyloid (Aβ42), phospho‐tau (p‐tau), and total tau (t‐tau). MBI status was derived from the NPI using a published algorithm. For each visit MBI+ was defined as an MBI score >0 and MBI‐ as MBI=0. Participants with MBI+ at both baseline and 1‐year visits were classified as having persistent NPS (i.e., MBI). An MBI+ score at only one visit was considered as transient NPS not consistent with MBI, and two consecutive MBI‐ visits were classified as no NPS. CSF protein values were log transformed due to skewness. Linear regressions were fitted to assess the association between NPS status and CSF biomarkers (Aβ42, p‐tau, t‐tau, and the derived measures p‐tau/Aβ42 and t‐tau/Aβ42), controlling for age, sex, education, and mini‐mental state examination. Result The sample of 480 participants had a mean age of 72.6 (SD 7.6); 195 (40.6%) were female. Compared to participants with no NPS, persistent NPS (i.e., MBI) was associated with lower CSF Aβ42 levels (p=0.02), higher CSF p‐tau (p=0.01) and t‐tau levels (p=0.026), and higher p‐tau/Aβ42 (p=0.002) and t‐tau/Aβ42 ratios (p=0.003) in adjusted models. Transient symptoms had CSF measures that did not differ from the no NPS group (Table 1). Conclusion In older adults with MCI, MBI was associated with abnormal CSF biomarkers of amyloid, tau and neurodegeneration. In this sample, MBI served as a marker to capture a group with greater AD neuropathological burden, extending the literature linking MBI with higher risk for AD. The findings emphasize the importance of appropriately ascertained NPS, in this case with respect to symptom persistence, in dementia detection and prognostication.

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