Abstract
INTRODUCTION: Despite advances in biomarker assessment, molecular neuroimaging, and disease-modifying therapies for cognitive disorders, China lacks well-characterized clinical cohorts integrating comprehensive clinical assessments and multimodal biomarkers. METHODS: The Shanghai Memory Study (SMS), an ongoing hospital-based cohort, enrolled participants undergoing clinical/neuropsychological assessments, genotyping, multimodal imaging, and biospecimen collection. RESULTS: From 2012 to 2024, 2001 participants were enrolled: 115 cognitively unimpaired (CU), 938 with mild cognitive impairment (MCI), and 948 with dementia. Positron emission tomography (PET) scan revealed A+/T+ positivity rates of 15.8% in CU, 51.2% in MCI, and 100% in Alzheimer's disease dementia (ADD). Plasma tau phosphorylated at threonine 181 (p-tau181) level increased gradually across the AD continuum. Blood p-tau181 and 18F-Florzolotau PET showed comparable utility for amyloid status identification. In a subcohort of 251 amnestic MCI (aMCI) patients, low Aβ42/Aβ40 and elevated p-tau181 predicted 4.7-year ADD risk. DISCUSSION: By offering an integrated framework, SMS will facilitate the exploration of AD pathogenesis and the understanding of cognitive disorders. HIGHLIGHTS: The SMS is an ongoing prospective cohort study based on a memory clinic in China. The SMS has established a relatively large-scale dataset that includes clinical data, biofluid markers, MRI and PET imaging, and novel biomarkers. By offering an integrated framework, SMS aims to facilitate the exploration of AD pathogenesis and deepen our understanding of cognitive disorders.