Drawing a Line: Differentiating Mild from Moderate Dementia Using the Functional Activities Questionnaire - 19/06/26
, Lukas Preis 1, 2, Aykut Aktuz 4, 1, Louise Droste 1, 2, 3, Akin Erman 1, 3, Daria Gref 1, 2, 3, Katharina Sophie Strentz 1, 2, 3, Julian Hellmann-Regen 1, 2, 3for the
Alzheimer’s Disease Neuroimaging Initiative* and the Frontotemporal Lobar Degeneration Neuroimaging Initiative**
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Highlights |
• | The FAQ distinguishes mild from moderate dementia with high sensitivity. |
• | Two clinically interpretable cut-offs (≥18 and ≥23) are proposed. |
• | Thresholds were validated across independent multicenter cohorts. |
Abstract |
BACKGROUND |
Accurate differentiation between mild and moderate dementia is increasingly important, particularly as amyloid-targeting therapies are restricted to early disease stages. Functional impairment in instrumental activities of daily living is a hallmark of progression beyond mild dementia. The informant-based Functional Activities Questionnaire (FAQ) is widely used, but empirically validated cut-offs distinguishing mild from moderate dementia remain insufficiently defined.
METHODS |
The optimal cut-off score was derived from the entire National Alzheimer’s Coordinating Center (NACC) Uniform Data Set as a discovery cohort (n = 34,513) and validated in two independent multicentric cohorts (Alzheimer’s Disease Neuroimaging Initiative (ADNI) n = 381 and Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) n = 74). The dementia staging was based on the Clinical Dementia Rating (CDR) global score. Functional impairment was assessed using the 10-item FAQ. Receiver operating characteristic analyses in NACC identified optimal thresholds, which were applied unchanged in validation cohorts. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated, and discordant cases were examined to identify factors associated with misclassification.
RESULTS |
In NACC, the FAQ demonstrated excellent discrimination of moderate dementia (AUC=0.947, 95% CI 0.944–0.949). A cut-off value of ≥18 maximized discrimination (sensitivity 96%, specificity 87%). A higher threshold of ≥23 improved specificity (92%) while maintaining 83% sensitivity. In ADNI and FTLDNI, the ≥18 threshold yielded sensitivities of 92% and 94%, respectively. The ≥23 threshold increased specificity across cohorts with acceptable sensitivity. Moreover, older age and lower cognitive performance were associated with higher odds of misclassification.
CONCLUSIONS |
The FAQ robustly differentiates mild from moderate dementia across diverse cohorts. A threshold of ≥18 prioritizes sensitivity, whereas ≥23 favors specificity, supporting context-dependent functional staging in clinical and research settings. Individuals with FAQ scores between 18 and 22 may benefit from more detailed clinical staging.
Il testo completo di questo articolo è disponibile in PDF.Keywords : Functional Activities Questionnaire, dementia staging, instrumental activities of daily living, Alzheimer's disease
Mappa
| *Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: ADNI_Acknowledgement_List . pdf |
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| **Data used in preparation of this article were obtained from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) database. The investigators at NIFD/FTLDNI contributed to the design and implementation of FTLDNI and/or provided data, but did not participate in analysis or writing of this report (unless otherwise listed). The FTLDNI investigators included the following individuals: Howard Rosen; University of California, San Francisco (PI); Bradford C. Dickerson; Harvard Medical School and Massachusetts General Hospital; Kimoko Domoto-Reilly; University of Washington School of Medicine; David Knopman; Mayo Clinic, Rochester; Bradley F. Boeve; Mayo Clinic Rochester; Adam L. Boxer; University of California, San Francisco; John Kornak; University of California, San Francisco; Bruce L. Miller; University of California, San Francisco; William W. Seeley; University of California, San Francisco; Maria-Luisa Gorno-Tempini; University of California, San Francisco; Scott McGinnis; University of California, San Francisco; Maria Luisa Mandelli; University of California, San Francisco |
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