Cognitive Profiles in Early- and Late-Onset Alzheimer's Disease: The Role of Dementia Severity in Typical Amnestic Presentations Using the Addenbrooke's Cognitive Examination III.

INTRODUCTION: Early-Onset (EOAD) and Late-Onset Alzheimer's Disease (LOAD) are often described as presenting distinct cognitive phenotypes. However, reported differences are inconsistent and may reflect demographic and severity-related confounding rather than stable etiological distinctions.

MATERIALS AND METHODS: A retrospective analysis was conducted in 776 patients with clinically diagnosed Alzheimer's disease (EOAD, n = 175; LOAD, n = 601). Cognitive performance was assessed using the Addenbrooke's Cognitive Examination III (ACE-III) and the Mini-Mental State Examination (MMSE). Dementia severity was staged using the Functional Assessment Staging Tool (FAST). Cognitive outcomes were analysed using age- and severity-adjusted ANCOVA models including a diagnosis × age interaction. Severity-stratified and domain-level analyses were also performed.

RESULTS: Unadjusted analyses revealed limited EOAD-LOAD differences in the Attention and Visuospatial domains, with small effect sizes. After adjustment for demographic variables and dementia severity, no cognitive measure reliably differentiated EOAD from LOAD. Cognitive performance showed similar cross-sectional patterns across groups and was primarily determined by dementia severity.

DISCUSSION: Small, stage-dependent differences observed at mild and moderate stages did not persist in more advanced dementia and did not indicate stable cognitive dissociation between EOAD and LOAD.

CONCLUSIONS: After adjustment for demographic factors and dementia severity, EOAD and LOAD do not exhibit distinct cognitive profiles on ACE-III. Cognitive performance reflects disease stage rather than age at onset, supporting the use of ACE-III for staging cognitive impairment rather than for differentiating EOAD from LOAD in typical amnestic presentations.