Prevalence and Risk Factors of Open-Angle Glaucoma in an Adult Chinese American Population: The Chinese American Eye Study.

Alzheimer's disease (AD) is characterized by its distinct neuropathological changes, including the accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles, which serve as the basis for diagnosis and staging of disease severity. However, the clinical presentation of AD is highly heterogeneous, with individuals exhibiting a wide spectrum of clinical impairment, ranging from asymptomatic to various amnestic and non-amnestic dementia presentations. In 2012, the National Institute on Aging and the Alzheimer's Association introduced guidelines that formally distinguished the neuropathological definition of AD from its clinical manifestations. This paradigm shift recognized that evidence of AD pathology could exist in individuals without overt cognitive impairment, emphasizing the potential dissociation between neuropathological AD stage and clinical symptoms. The development of biomarkers for AD neuropathological changes has enabled the identification and staging of AD pathology in living individuals. In 2024, the Alzheimer's Association proposed an updated staging framework integrating biological and clinical disease staging systems. This revised model posits that clinical severity and biological AD stage are quasi-independent variables, acknowledging that their relationship is influenced by interindividual differences in co-pathologies, cognitive and brain reserve, and social determinants of health. Although biological AD stage and clinical severity are related, they are hypothesized not to progress in a fixed manner across all individuals, reflecting the inherent heterogeneity of the disease. Two recent studies in highly selected populations reported only limited concordance between biological AD stages and clinical severity. One study also used emerging biomarkers to examine the role of co-pathologies, such as α-synuclein and vascular disease, in clinical–biological associations. However, no study has yet investigated the influence of other pathologies associated with dementia, such as frontotemporal lobar degeneration (FTLD)-tau, FTLD-TDP-43 and limbic-predominant age-related TDP43 encephalopathy neuropathological change (LATE-NC), using gold-standard neuropathological assessments.