DOI: 10.1002/alz.072704 ISSN: 1552-5260

A longitudinal multimodal biomarker study of memory clinic MCI patients with MBI – are there links to Alzheimer disease?

Zahinoor Ismail, Rebeca Leon, Hung‐ Yu Chen, Philippe Robert, Eric E. Smith
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Mild cognitive impairment (MCI) and mild behavioral impairment (MBI) are at‐risk states for incident dementia. MBI represents behavioral risk, and MCI represents cognitive risk. In memory clinic MCI patients, we interrogated the relationship between MBI status (+/‐), cerebral atrophy, cerebrospinal fluid (CSF) biomarkers, and incident all‐cause dementia and incident Alzheimer disease (AD) dementia.


MBI was operationalized as persistent neuropsychiatric symptoms (NPS) in MEMENTO study participants. MRI regions were selected a priori for Braak stages I‐V. CSF markers included amyloid‐β (Aβ), hyperphosphorylated‐tau (p‐tau), and tau. Linear regression models were fitted with regional thickness/volume or CSF markers as dependent variables, and MBI status as independent variable, adjusted for age, sex, and education. Logistic regression was conducted to investigate if MBI status was associated with amyloid‐β positivity (defined as <813 pg/mL), with MBI status as predictor, adjusting for age, sex, education and MMSE. Kaplan‐Meier curves were generated for dementia‐free survival out to 6 years. Cox proportional hazard regressions, adjusted for age, sex, education, MMSE score, and MCI subtype were utilized to investigate the rates of incident all‐cause dementia, as well as incident AD dementia, in MBI+ vs MBI‐ patients with MCI.


Of the 820 participants (mean age(±SD) 72.54(8.21), 57.80% female), 29.5% had MBI. Compared to MBI‐, MBI+ status was associated with lower entorhinal thickness (b = –0.066, p = 0.04) and smaller hippocampal volume (b = –0.069, p< 0.01). In the CSF subsample (n = 154, mean age = 69.6, 48.1% female), MBI predicted amyloid‐β positivity (odds ratio = 2.19, p = 0.05), and was associated with 7.4% lower Aβ42 level (p = 0.01), 17.8% higher CSF p‐tau/Aβ42 (p<0.01) and 18.9% higher t‐tau/Aβ42 ratio (p = 0.02). Longitudinally, MBI+ had lower dementia‐free survival (log rank test; p<0.0001), with adjusted hazard ratios (HRs) of 2.76 (95%CI 1.99‐3.8; p<0.001) for all‐cause dementia and 2.73 (95%CI 1.83‐4.07; p<0.001) for AD dementia.


MBI served as a clinical marker to identify a subgroup of MCI patients with Alzheimer disease‐related morphological changes in the entorhinal cortex and hippocampus, and CSF biomarkers consistent with AD. MCI with MBI had a greater incidence rate of AD dementia than MCI without MBI. MBI case status may be used to improve detection of prodromal AD in MCI.

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