Establishing diagnostic thresholds for Alzheimer's disease in adults with Down syndrome: the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS)

Abstract

Background Diagnosis of prodromal Alzheimer's disease and Alzheimer's disease dementia in people with Down syndrome is a major challenge. The Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) has been validated for diagnosing prodromal Alzheimer's disease and Alzheimer's disease dementia, but the diagnostic process lacks guidance. Aims To derive CAMDEX-DS informant interview threshold scores to enable accurate diagnosis of prodromal Alzheimer's disease and Alzheimer's disease dementia in adults with Down syndrome. Method Psychiatrists classified participants with Down syndrome into no dementia, prodromal Alzheimer's disease and Alzheimer's disease dementia groups. Receiver operating characteristic analyses assessed the diagnostic accuracy of CAMDEX-DS informant interview-derived scores. Spearman partial correlations investigated associations between CAMDEX-DS scores, regional Aβ binding (positron emission tomography) and regional cortical thickness (magnetic resonance imaging). Results Diagnostic performance of CAMDEX-DS total scores were high for Alzheimer's disease dementia (area under the curve (AUC), 0.998; 95% CI 0.953–0.999) and prodromal Alzheimer's disease (AUC = 0.954; 95% CI 0.887–0.982) when compared with healthy adults with Down syndrome. When compared with those with mental health conditions but no Alzheimer's disease, CAMDEX-DS Section B scores, denoting memory and orientation ability, accurately diagnosed Alzheimer's disease dementia (AUC = 0.958; 95% CI 0.892–0.984), but were unable to diagnose prodromal Alzheimer's disease. CAMDEX-DS total scores exhibited moderate correlations with cortical Aβ (r ~ 0.4 to 0.6, P ≤ 0.05) and thickness (r ~ −0.4 to −0.44, P ≤ 0.05) in specific regions. Conclusions CAMDEX-DS total score accurately diagnoses Alzheimer's disease dementia and prodromal Alzheimer's disease in healthy adults with Down syndrome.