AbstractBackgroundMild behavioural impairment (MBI) is characterized by late‐life emergent and persistent neuropsychiatric symptoms (NPS). It is as an at‐risk state for incident cognitive decline and dementia. For some, MBI may be the first observable manifestation of a neurodegenerative process such as Alzheimer’s disease (AD).MethodsWe examined associations between MBI and established dementia imaging and CSF markers, in 789 participants with mild cognitive impairment (MCI). Study data were obtained from the French MEMENTO cohort study.Neuropsychiatric Inventory (NPI) scores were used to determine MBI scores using a published algorithm. NPI data at baseline and 6‐month visits were used to categorize patients into MBI+ (persistent NPS i.e., NPS at both time points) and MBI‐ (no NPS or NPS at either but not both time points). MRI and CSF measurements were completed at baseline. Linear regressions were fitted to assess if MBI status at 6 months was associated with reduced thickness or volume in each of the a priori selected regions associated with Braak stages 1‐5: entorhinal cortex, hippocampus, fusiform gyrus, inferior temporal cortex and frontal pole. To assess if MBI status was associated with CSF biomarkers (Aβ42, Aβ40, t‐tau, p‐tau, Aβ42/Aβ40, p‐tau/Aβ42 and t‐tau/Aβ42), seven linear regressions were conducted. All models controlled for age, sex, education, and mini‐mental state examination scores. Volume and thickness analysis further controlled for total intracranial volume.ResultsMBI+ (persistent NPS) status was associated with decreased entorhinal thickness and smaller hippocampal volume compared to MBI‐ (Table 1). There were no differences between MBI+ and MBI‐ groups in thickness of the Braak stage 3‐5 regions (Table 1). In the subset of MCI participants with CSF data (n=155), compared to MBI‐, MBI+ had lower CSF Aβ42 levels, higher CSF p‐tau/Aβ42 and t‐tau/Aβ42 ratios (Table 2).ConclusionIn a memory clinic sample of older adults with MCI, MBI was associated with AD markers and served as a proxy marker to capture AD changes in a non‐demented sample. These findings extend the literature linking MBI with known dementia biomarkers and emphasize the importance of appropriately ascertained NPS, in this case with respect to symptom persistence, in dementia detection and prognostication.