Biomarkers

Area of Science:

• Neuroscience
• Neurology
• Gerontology

Background:

• Neuropsychiatric symptoms are common in dementia, often appearing early.
• Mild behavioral impairment (MBI) in non-demented individuals shows variable links to neurodegeneration.
• This study examines MBI's relationship with brain glucose metabolism in autosomal-dominant Alzheimer's disease (AD).

Purpose of the Study:

• To investigate the association between Mild Behavioral Impairment (MBI) and cerebral glucose metabolism.
• To explore the role of MBI as a potential early indicator of neurodegeneration in autosomal-dominant Alzheimer's disease (AD).
• To determine if Alzheimer's disease pathology mediates the relationship between MBI and brain metabolism.

Main Methods:

• Utilized data from the Colombia-Boston (COLBOS) Biomarkers Study, including Presenilin-1 E280A mutation carriers and non-carriers.
• Assessed MBI using the MBI-Checklist (MBI-C) and measured cerebral glucose metabolism via 18F-fluorodeoxyglucose (FDG) PET in the precuneus.
• Conducted mediation analysis with amyloid and tau PET data to assess the role of AD pathology.

Main Results:

• MBI positivity was significantly higher in mutation carriers (68%) versus non-carriers (35%).
• Participants with MBI showed reduced precuneus glucose metabolism (FDG uptake), particularly among carriers.
• Alzheimer's disease pathology partially mediated the association between MBI and reduced FDG uptake.

Conclusions:

• MBI is associated with hypometabolism in early AD-related regions in mutation carriers, partly due to AD pathology.
• These findings suggest MBI may precede neurodegeneration and cognitive impairment, potentially serving as an early risk factor for AD progression.
• Further research with larger sample sizes is needed to validate MBI as a marker for identifying individuals at high risk for AD and for prevention strategies.