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

Abstract

Alzheimer'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. An 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. Age (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. Concluding 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. 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.