The Role of Physical Fitness in Cognitive-Related Biomarkers in Persons at Genetic Risk of Familial Alzheimer’s Disease

Introduction: Nondemented people with a family history of Alzheimer’s disease (ADFH) and the ApoE-4 allele have been demonstrated to show a trend for a higher probability of cognitive decline and aberrant levels of cognitive-related biomarkers. However, the potential interactive effects on physical fitness have not been investigated. Purpose: The primary purpose of this study was to determine whether ADFH individuals with the ApoE-4 genotype show deviant brain event-related neural oscillatory performance and cognitively-related molecular indices. A secondary purpose was to examine the interactive effects on physical fitness. Methods: Blood samples were provided from 110 individuals with ADFH to assess molecular biomarkers and the ApoE genotype for the purpose of dividing them into an ApoE-4 group (n = 16) and a non-ApoE-4 group (n = 16) in order for them to complete a visuospatial working memory task while simultaneously recording electroencephalographic signals. They also performed a senior functional physical fitness (SFPF) test. Results: While performing the cognitive task, the ApoE-4 relative to non-ApoE-4 group showed worse accuracy rates (ARs) and brain neural oscillatory performance. There were no significant between-group differences with regard to any molecular biomarkers (e.g., IL-1β, IL-6, IL-8, BDNF, Aβ1-40, Aβ1-42). VO(2max) was significantly correlated with the neuropsychological performance (i.e., ARs and RTs) in the 2-item and 4-item conditions in the ApoE-4 group and across the two groups. However, the electroencephalogram (EEG) oscillations during visuospatial working memory processing in the two conditions were not correlated with any SFPF scores or cardiorespiratory tests in the two groups. Conclusions: ADFH individuals with the ApoE-4 genotype only showed deviant neuropsychological (e.g., ARs) and neural oscillatory performance when performing the cognitive task with a higher visuospatial working memory load. Cardiorespiratory fitness potentially played an important role in neuropsychological impairment in this group.