Alzheimer's Disease biomarkers analysis in a cohort of normal elderly, elderly with subjective cognitive decline and elderly with exceptional performance memory

Abstract

Based on the amyloid cascade model, Alzheimer's disease preclinical stage would start by a stage of cerebral amyloidosis, after a stage of amyloidosis plus neurodegeneration and finally a stage of subtle cognitive decline. This subtle cognitive decline is characterized by individual experience of subjective deterioration in their cognitive performance, it not detected objectively by formal neuropsychological tests. Several epidemiological studies have shown that individuals with subjective decline have increased risk of progression to dementia from Alzheimer's disease. Additionally, there is evidence of a greater prevalence of positive biomarkers for amyloidosis and neurodegeneration. Consequently, these findings suggest that subjective cognitive complaints may be an early clinical marker of the disease. On the other hand, there are elderly whose aging is not accompanied by a decline in cognitive abilities. This group, known as "SuperAgers", constitutes octa and nonagenarian elderly whose performance in memory tests equates to individuals 20 to 30 years younger. Objectives: To analyze and compare the presence of Alzheimer's disease biomarkers in a cohort of normal elderly, elderly with subjective cognitive decline and elderly with exceptional memory performance ("SuperAgers"). Secondary objectives are to compare the longitudinal performance in neuropsychological tests, to analyze sensitivity of short-term memory binding as subjective cognitive decline marker, to compare the anatomic regions commonly more vulnerable to Alzheimer's disease as the cortical thickness, glycolytic metabolism and deposition of beta-amyloid peptide and, finally, to investigate the presence of E4 allele of APOE associated with increased prevalence of subjective cognitive decline. Methodology: The sample consists of healthy elderly subjects recruited from the Geriatrics Service of Clinical Hospital of the Medical School of the University of São Paulo. Volunteers will be divided into three groups: normal controls, elderly with subjective cognitive decline and octa / nonagenarian elderly with exceptional memory performance (or SuperAgers). The three groups will be followed longitudinally for three years and compared for the possibility or not of biomarkers (beta-amyloid peptide on PET-CT PiB and neuronal injury on PET-CT FDG and cortical atrophy on structural MRI) and for performance on formal neuropsychological testing. (AU)