Maas_2026_Sci.Rep_16_

Early stages of Alzheimer's Disease (AD), commonly referred to as early AD (eAD), represent a critical phase for timely diagnosis and intervention. However, significant gaps remain in understanding real-world care of individuals initiating first-line treatment such as acetylcholinesterase inhibitors (AChE-I) in Germany. A retrospective study was conducted using the German InGef claims database with a pragmatic proxy approach, identifying de novo AChE-I initiators as individuals suspected of having eAD. Two cohorts were defined: a pre-cohort (2022) capturing eight-years prior to AChE-I initiation, and a post-cohort (2017), analyzing five-years following initiation. Patients were matched 1:1 to controls without AD based on demographic characteristics. Outcomes included comorbidities, risk factors, diagnostics, prescriptions, and survival. The study identified 1,994 (pre-cohort) and 2,051 (post-cohort) AChE-I initiators, and respective controls. Mobility disorders increased significantly (+ 55%) over the eight years preceding treatment. Eight years pre-initiation, 81.9% of initiators exhibited at least one modifiable risk factor compared to 76.2% in controls (p < 0.001). Advanced diagnostic procedures were underutilized (MRI: 39.0%, cerebrospinal fluid analysis: 9.2%, in year -1). Only 78.6% received an AD-specific diagnosis within the first year post-initiation. Extensive use of psycholeptics and psychoanaleptics was observed, with a notable decline in dementia-specific medications post-initiation. Post-initiation, initiators showed higher comorbidity burden (e.g., urinary incontinence: 40.2% vs. 10.7% by year 5) and higher observed, unadjusted mortality (53.3% vs. 21.7%, p < 0.001). This study highlights patterns suggestive of gaps in the management of AChE-I initiators in Germany, including underutilization of guideline-based diagnostics, high comorbidity burden, and higher observed mortality. Improved management strategies and the development of more precise diagnostic coding that reflects disease stages could help to address these issues.