Current Diagnostic Pathways for Alzheimer’s Disease: A Cross-Sectional Real-World Study Across Six Countries

Abstract

Background: Diagnostic pathways for patients presenting with cognitive complaints may vary across geographies. Objective: To describe diagnostic pathways of patients presenting with cognitive complaints across 6 countries. Methods: This real-world, cross-sectional study analyzed chart-extracted data from healthcare providers (HCPs) for 6,744 patients across China, France, Germany, Spain, UK, and the US. Results: Most common symptoms at presentation were cognitive (memory/amnestic; 89.86%), followed by physical/behavioral (87.13%). Clinical/cognitive tests were used in > 95%, with Mini-Mental State Examination being the most common cognitive test (79.0%). Blood tests for APOE ɛ4/other mutations, or to rule out treatable causes, were used in half of the patients. Clinical and cognitive tests were used at higher frequency at earlier visits, and amyloid PET/CSF biomarker testing at higher frequency at later visits. The latter were ordered at low rates even by specialists (across countries, 5.7% to 28.7% for amyloid PET and 5.0% to 27.3% for CSF testing). Approximately half the patients received a diagnosis (52.1% of which were Alzheimer’s disease [AD]). Factors that influenced risk of not receiving a diagnosis were HCP type (higher for primary care physicians versus specialists) and region (highest in China and Germany). Conclusion: These data highlight variability in AD diagnostic pathways across countries and provider types. About 45% of patients are referred/told to ‘watch and wait’. Improvements can be made in the use of amyloid PET and CSF testing. Efforts should focus on further defining biomarkers for those at risk for AD, and on dismantling barriers such low testing capacity and reimbursement challenges.

Blood‐based biomarkers in Alzheimer's disease: Future directions for implementation

“…The parallel qualitative study performed 32 revealed that a higher rate of diagnosis among patients presenting to a specialist versus a PCP (∼60% vs. ∼30%).…”

“…The advisory boards noted that symptomatic patients with a negative blood test still need to be referred, as AD is not the only cause of cognitive impairment (although the most common 43 ). Data suggesting that many patients have inconclusive outcomes such as "watch and wait" 32 support the role of a simple BBBM test to detect amyloid pathology and create a consistent and efficient pathway to confirmatory PET/CSF testing.…”

“…This is supported by the literature, with minority ethnic groups presenting to therapeutic and diagnostic services at a late stage in their illness, 41 with an additional delay of ≤7 years between first symptoms and physician consultation. 42 The parallel qualitative study performed 32 revealed that a higher rate of diagnosis among patients presenting to a specialist versus a PCP (∼60% vs. ∼30%).…”

Clinical application of plasma P-tau217 to assess eligibility for amyloid-lowering immunotherapy in memory clinic patients with early Alzheimer’s disease

“…4 Remaining sample size after removal of 5 intermediate cases. 5 Site-speci c cutoffs identi ed 3 Aβ positive and 3 Aβ negative participants in the intermediate "gray zone" (6/50 = 12%).…”

“…The recent Food and Drug Administration (FDA) approval of amyloid-lowering immunotherapies, such as aducanumab and lecanemab, necessitates the optimization of screening techniques for Aβ pathology, as biomarker con rmation of Aβ status is required prior to treatment (3,4). This important requirement represents a major barrier to treatment access for many patients due to current reliance on invasive and expensive positron emission tomography (PET) or cerebrospinal uid (CSF) testing (5), and may compound existing racial and ethnic inequalities in AD treatment (6-9). The development of a minimally invasive and costeffective screening method to facilitate early detection and intervention is, therefore, of high clinical importance in expanding equitable access to new and forthcoming treatments for early AD (1,10).…”