The complexities of diagnosing young-onset Alzheimer's dementia and the need for swift identification

Young-onset Alzheimer's disease (YOAD), defined by symptom onset before 65 years, represents a distinct subtype of Alzheimer's disease with important diagnostic and therapeutic implications. Compared with late-onset Alzheimer's disease (LOAD), YOAD shows greater phenotypic heterogeneity, more frequent atypical non-amnestic presentations, and a stronger genetic contribution, leading to a delay in diagnosis and a substantial psychosocial burden.

This review summarizes the current evidence on epidemiology, genetics, clinical phenotypes, and diagnostic strategies. YOAD differs from LOAD in terms of broader differential diagnoses and atypical cognitive syndromes. Advances in biomarker-based diagnostics, neuroimaging, and blood-based markers, are discussed, with an emphasis on early detection, patient stratification, and relevance for emerging disease-modifying therapies. A systematic PubMed literature search covering the years 2010 to 2026, used search terms related to YOAD, clinical phenotypes, biomarkers, neuroimaging, and genetic factors.

YOAD remains underrecognized and diagnostically challenging, limiting timely access to targeted therapies. The integration of multimodal biomarkers and genetic testing is essential for early diagnosis, as is the need for a comprehensive neuropsychological assessment to capture atypical phenotypes. Future neurotherapeutic strategies also require age-specific approaches and the adaptation of health care systems to address the distinct clinical and socioeconomic needs in YOAD.