Drawing a line: Differentiating mild from moderate dementia using the functional activities questionnaire.

Area of Science:

• Neurology
• Geriatrics
• Neuroscience

Background:

• Accurate differentiation between mild and moderate dementia is crucial for early intervention, especially with emerging amyloid-targeting therapies.
• Functional impairment in instrumental activities of daily living is a key indicator of dementia progression.
• The informant-based Functional Activities Questionnaire (FAQ) is widely used but lacks empirically validated cut-offs for distinguishing dementia severity.

Purpose of the Study:

• To establish empirically validated cut-off scores for the Functional Activities Questionnaire (FAQ) to differentiate mild from moderate dementia.
• To validate these cut-offs in independent, diverse patient cohorts.

Main Methods:

• Utilized a large discovery cohort (NACC, n=34,513) to derive optimal FAQ thresholds using receiver operating characteristic analyses.
• Validated the derived thresholds in two independent multicentric cohorts (ADNI, n=381; FTLDNI, n=74).
• Dementia staging was based on the Clinical Dementia Rating (CDR) global score; functional impairment assessed via the 10-item FAQ.

Main Results:

• The FAQ demonstrated excellent discrimination of moderate dementia in the NACC cohort (AUC=0.947).
• A cut-off of ≥18 provided high sensitivity (96%) and specificity (87%), while ≥23 improved specificity (92%) with maintained sensitivity (83%).
• Validation cohorts showed high sensitivity for the ≥18 threshold (ADNI: 92%, FTLDNI: 94%); older age and lower cognition were linked to misclassification.

Conclusions:

• The FAQ reliably differentiates mild from moderate dementia across different cohorts.
• A threshold of ≥18 maximizes sensitivity, while ≥23 maximizes specificity, allowing for context-dependent staging.
• Individuals with FAQ scores of 18-22 may require further detailed clinical evaluation for precise staging.