ALZHEIMER'S DISEASE BIOMARKERS IN ELDERLY PATIENTS SUBMITTED TO ELECTIVE SURGERIES UNDER SPINAL ANESTHESIA: CONTRIBUTION TO THE STUDY OF POSTOPERATIVE COGNITIVE DYSFUNCTION AND EARLY DIAGNOSIS OF DEMENTIA

• Grant number: 24/02946-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2024
• Effective date (End): August 31, 2025
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Maria José Carvalho Carmona
• Grantee: Matheus Bravo Martinez
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia in the elderly.It begins with Mild Cognitive Impairment (MCI) but can progress to a high degree of brain degeneration, includingsymptoms such as amnesia (a typical symptom) and behavioral changes such as depression, anxiety, psychomotoragitation, and sleep disturbances. In advanced stages, the disease necessitates assistance for basic functions. Inparallel, Postoperative Cognitive Dysfunction (POCD) is a condition resulting from anesthesia-surgical trauma,measurable through neuropsychological tests administered before and after surgeries, and is associated with a morepronounced cognitive decline than expected for age. Recent research has shown the possibility of diagnosing AD inasymptomatic individuals through laboratory tests (cerebrospinal fluid biomarkers) and/or molecular imaging methods('amyloid-' and 'tau-PET'). This study is a cross-sectional analysis of a cohort comprising 894 individuals undergoingelective surgical procedures under spinal anesthesia or general anesthesia associated with subarachnoid puncture forpostoperative analgesia. The study participants are from the Urology, Orthopedics, and Gynecology services atHCFMUSP. The study aims to: (1) determine the concentrations of AD cerebrospinal fluid biomarkers (A²1-42 peptideand Tau protein) in elderly individuals undergoing spinal anesthesia for elective surgical procedures, stratified by thepresence of memory complaints and overall cognitive functioning level (normal cognition, MCI, or dementia); (2) assessthe correlation between the positivity of these biomarkers (indicating patterns suggestive of AD) and the occurrence ofsymptoms and/or cognitive deficits in the evaluated individuals; (3) exploratorily determine a set of peripheral bloodbiological markers (candidate biomarkers) and their potential correlations with biomarker concentrations in individualswith normal cognitive function, those with biomarker positivity, characterizing pre-clinical AD cases; and (5) investigatewhether the identification of cognitive alterations and the presence of cerebrospinal and serum markers for AD correlatewith the incidence of POCD. Baseline neurocognitive status will be inferred through 10-CS, Clock Drawing Test, MoCA,verbal fluency test (phonemic and semantic), GDS-15, and Hamilton scale (HAM-D 21), performed in the surgical riskoutpatient clinic the day before the procedure. Initially, 40ml of blood will be collected after venous function.Subsequently, cerebrospinal fluid will be collected from sedated patients (Fentanyl 10 to 50 mcg), with venous access,in a seated position. After asepsis with alcoholic chlorhexidine, a median or paramedian puncture will be performed atthe level of the lumbar vertebrae L2-L3, L3-L4, or L4-L5, using a 25G Quincke needle, and 3 ml of cerebrospinal fluidwill be collected without blood residues. For the analysis of the collected samples, the commercially available Milliplex kit(Merk-Millipore) will be used to determine the concentrations of A²1-42, T-Tau, and P-Tau proteins, and TaqmanGenotyping PCR assays (Life Technologies) will be used for the rs429358 and rs7412118 polymorphisms - APOEgenotyping. After 30 days, neurocognitive tests will be repeated