Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by cognitive, functional, and behavioural decline. Despite a general trend of deterioration, substantial heterogeneity exists in progression patterns. Understanding this variability is critical for accurate diagnosis, prognosis, personalized care, caregiver support, and clinical trial design. This study aimed to characterize cognitive trajectories in AD and explore cross-national differences.
Methods: This retrospective, observational study analysed longitudinal data from medical chart reviews at 26 sites across France, Germany, Italy, Spain, and the UK. Patients over 55 years with probable AD and Mini-Mental State Examination (MMSE) score between 20 and 28 at diagnosis were included. Exclusion criteria were history of stroke or transient ischemic attack, Parkinson’s disease prior to or at AD onset, frontotemporal dementia, or probable Lewy body disease.
Data included demographics, comorbidities, clinical characteristics, AD diagnostic and treatment pathways, and longitudinal outcomes across cognitive, functional, and behavioural domains. Change-point analysis and latent class growth modeling (LCGM) were used to identify cognitive decline trajectories. Country-specific analyses assessed heterogeneity in patient profiles and disease progression.
Results: LCGM identified three cognitive decline trajectories—slow, moderate, and rapid—with a classification accuracy of 95.4%. The analysis included 800 patients with a median follow-up of 4.42 years. Cross-country differences were observed in diagnostic practices and assessment tools with over 32 instruments used across sites.
Conclusion: This multinational study highlights heterogeneity in cognitive trajectories and diagnostic practices in AD, emphasizing the need for harmonized assessments to standardized clinical care and trial design.