Anxiety in Alzheimer's disease rats is independent of memory and impacted by genotype, age, sex, and exercise

Abstract

AbstractINTRODUCTIONAlzheimer's disease (AD) is characterized by cognitive impairments; however, heightened anxiety often accompanies and, in some cases, exacerbates cognitive its. The present study aims to understand the influence of multiple variables on anxiety‐like behavior in TgF344‐AD rats and determine whether anxiety impacts memory performance.METHODSAn elevated plus maze was used to assess anxiety‐like behavior in the established colony (n = 107). Influences of age, sex, genotype, and exercise on anxiety were evaluated via multiple linear regression. Correlation analysis evaluated the relationship between anxiety and memory performance.RESULTSAge (P < 0.05) and AD genotype (P < 0.001) were associated with increasing anxiety, while exercise (P < 0.05) was associated with decreasing anxiety. Female AD animals displayed more anxiety‐like behavior versus wild‐type female (P < 0.001) and AD male (P < 0.05) littermates.DISCUSSIONConcluding that while factors such as age, sex, AD genotype, and training status can impact anxiety levels in the TgF344‐AD model, anxiety level did not impact memory performance.Highlights Increased anxiety‐like behavior in TgF344‐AD rats does not correlate with declines in memory performance. Predictors of higher anxiety‐like behaviors in the TgF344‐AD rat include age, Alzheimer's disease (AD) genotype, and sex with female AD animals experiencing greater anxiety compared to female wild‐type or male AD. Exercise training leads to decreased anxiety‐like behaviors in the TgF344‐AD rat.