Clinical Cohort of Memory Disorders

This observational clinical cohort links banked blood specimens with clinical and brain imaging data to support biomarker discovery and validation in memory disorders. The protocol specifies a multicenter design involving Severance Hospital, Gangnam Severance Hospital, and Yongin Severance Hospital. Planned enrollment is 1,550: 1,500 adults aged 50 years or older and 50 healthy controls aged 19-30 years (25 men and 25 women). Site targets are 550 at Severance Hospital, including the young controls, and 500 at each other site. The overall study period is 120 months from IRB approval.

Hospital attendees and young volunteers recruited through university notice boards and online advertisements will be enrolled by non-probability sampling after informed consent. Enrollment is independent of the specific medication received. For patients with limited consent capacity and MMSE scores below 15, additional family representative consent will be obtained under the approved consent procedures.

Prospective recruitment and specimen collection will be combined with collection of available clinical records, including records predating enrollment. Data include demographics, education, medical and family history, comorbidities, medication use, height, weight, waist circumference, laboratory findings, and cognitive and neuropsychological assessments. Measures described in the protocol include the Korean Mini-Mental State Examination, Seoul Neuropsychological Screening Battery, Clinical Dementia Rating, Global Deterioration Scale, and Short Geriatric Depression Scale. Available brain MRI and PET data will be collected and linked to clinical and biomarker findings. Additional diagnostic tests may be performed at the specialist's discretion when existing information is insufficient for diagnostic classification, with study support for the additional costs.

The target follow-up duration for the memory disorder cohort is 5 years. Available longitudinal clinical, cognitive, and imaging data will be collected; this target does not imply a uniform visit schedule or that every participant has already completed 5 years of follow-up. Additional blood sampling may be performed in treatment-related substudies according to the approved protocol and clinical course.

Young adult controls attend one visit for memory screening and blood collection. Assessments include demographics, height, weight, MMSE, Clinical Dementia Rating, Global Deterioration Scale, hematology, clinical chemistry, and APOE genotyping. Clinical chemistry includes liver and kidney function, glucose, and electrolytes to assess factors affecting biomarker interpretation.

At enrollment, a total of 6 mL of research blood will be collected for banking and separated into plasma and buffy coat aliquots for storage at -70°C in the designated freezer at the Avison Biomedical Research Center, Yonsei University College of Medicine, Seoul, South Korea. Buffy coat permits DNA extraction. Retention, secondary use, transfer, and disposal follow participant consent. Permission to use previously collected specimens will be reconfirmed and documented if consent is withdrawn.

Metabolomic and proteomic analyses will explore markers associated with diagnosis, severity, and clinical course using linked clinical and available imaging data. Candidate biomarkers may undergo further evaluation using immunoassays and biochemical or molecular methods, including cell or animal experiments where appropriate. Treatment effects and adverse effects may also be explored.

Data will be coded, with the identification key kept separately and access limited to authorized personnel. Paper records will be locked and electronic records password-protected. The principal investigator or a delegated investigator will monitor source documents, protocol adherence, and specimen management every 12 months. Procedure-related adverse events will be assessed and reported by the investigators.