Introduction: Simple markers are required to recognize older adults at higher risk for neurodegenerative disease. Mild behavioural impairment (MBI) and plasma β-amyloid (Aβ) have been independently implicated in the development of incident cognitive decline and dementia. Here we studied the associations between MBI and plasma Aβ42/Aβ40. Methods: Participants with normal cognition (n = 86) or mild cognitive impairment (n = 53) were selected from the Alzheimer’s Disease Neuroimaging Initiative. MBI scores were derived from Neuropsychiatric Inventory items. Plasma Aβ42/Aβ40 ratios were assayed using mass spectrometry. Linear regressions were fitted to assess the association between MBI total score as well as MBI domain scores with plasma Aβ42/Aβ40. Results: Lower plasma Aβ42/Aβ40 was associated with higher MBI total score ( p = 0.04) and greater affective dysregulation ( p = 0.04), but not with impaired drive/motivation ( p = 0.095) or impulse dyscontrol ( p = 0.29) MBI domains. Conclusion: In persons with normal cognition or mild cognitive impairment, MBI was associated with low plasma Aβ42/Aβ40. Incorporating MBI into case detection may help capture preclinical and prodromal Alzheimer’s disease.

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IntroductionSimple markers are required to recognize older adults at higher risk for neurodegenerative disease. Mild behavioural impairment (MBI) and plasma β-amyloid (Aβ) have been independently implicated in the development of incident cognitive decline and dementia. Here we studied the associations between MBI and plasma Aβ42/Aβ40.MethodsParticipants with normal cognition (n = 86) or mild cognitive impairment (n = 53) were selected from the Alzheimer’s Disease Neuroimaging Initiative. MBI scores were derived from Neuropsychiatric Inventory items. Plasma Aβ42/Aβ40 ratios were assayed using mass spectrometry. Linear regressions were fitted to assess the association between MBI total score as well as MBI domain scores with plasma Aβ42/Aβ40.ResultsLower plasma Aβ42/Aβ40 was associated with higher MBI total score (p = 0.04) and greater affective dysregulation (p = 0.04), but not with impaired drive/motivation (p = 0.095) or impulse dyscontrol (p = 0.29) MBI domains.ConclusionIn persons with normal cognition or mild cognitive impairment, MBI was associated with low plasma Aβ42/Aβ40. Incorporating MBI into case detection can help capture preclinical and prodromal Alzheimer’s disease.

Background: Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterized by the onset and persistence of neuropsychiatric symptoms (NPS) in later life. While the ATN framework provides a robust overview of Alzheimer's pathology, it does not fully capture the impact of small-vessel cerebrovascular disease in the pathogenesis of dementia. White matter hyperintensities (WMH) may independently contribute to the development of Alzheimer's dementia and predict risk of incident dementia in mild cognitive impairment (MCI). Few studies have established the link between NPS and WMH in MCI populations. Method:We included 760 participants from the French MEMENTO study with MCI and WMH data. WMH volumetry on T 2 -weighted fluid attenuated inversion recovery images was identified using WHASA software, visually verified with the Fazekas and Schmidt scale, and expressed in cm 3 . Mean age was 72.7 (SD 8.0) and 57.9% of participants were female. Neuropsychiatric Inventory items were transformed to MBI domains using a published algorithm. MBI status was based on symptom persistence: NPS at both baseline and 6-months was considered MBI+ (n = 227), whereas nonpersistent NPS (i.e., NPS at either time point but not both) or no NPS at either baseline or 6-months was considered MBI-(n=549). We investigated the association between MBI status and the outcome variable, WMH, using a linear regression model adjusted for age, sex, education, Mini-Mental Status Exam (MMSE) score, and total intracranial volume.Result: MBI was present in 29.9% of participants (n = 227). MBI+ (i.e., persistent NPS) was significantly associated with lower MMSE score (p < 0.001) and male sex (p = 0.025). Compared to MBI-, MBI+ was associated with 9.9% higher WMH volume [p = 0.006 (95% CI 2.8% to 18%), Table 1]. Conclusion:In a memory clinic sample of older adults with MCI, MBI+, operationalized as persistent NPS, is associated with higher WMH. These findings extend the evidence base linking MBI with known dementia biomarkers and raise the possibility that some forms of MBI can be caused by vascular brain injury.