Supplementary Material for: Differentiating behavioural presentations of biomarker-confirmed Alzheimer’s disease from frontotemporal lobar degeneration using the Addenbrooke's Cognitive Examination-III

Introduction: Differentiating frontotemporal lobar degeneration (FTLD) from Alzheimer’s disease (AD), particularly when presenting with overlapping behavioural symptoms, remains clinically challenging. This study assessed the utility of Addenbrooke's Cognitive Examination-III (ACE-III)-derived ratios in distinguishing these conditions.

Methods: A retrospective cohort of 115 patients (n=52 biomarker-confirmed AD, n=63 FTLD) with overlapping behavioural symptoms was analysed. ACE-III scores and behavioural profiles were examined, and novel ratios were tested.

Results: The novel Phonemic Fluency/Orientation-Memory (PFOM) ratio outperformed existing ACE-III metrics, achieving an area under the curve (AUC) of 0.85 (sensitivity 84.1%, specificity 73.1%) for differentiating FTLD from AD. Notably, longer symptom duration in AD, but not in FTLD, was associated with worsening frontal and cognitive symptoms. Patients with AD were significantly older than those with FTLD.

Discussion: These novel ratios showed robust diagnostic performance, regardless of disease duration, and better reflects FTLD's cognitive profile. It may offer improved clinical utility over traditional ACE-III measures.