Repeated Performance of Spatial Memory Tasks Ameliorates Cognitive Decline in APP/PS1 Mice

Background: Alzheimer's disease (AD) is a burden on the public health system because it is a neurodegenerative disease that is incurable and for which there is no successful treatment. AD patients suffer from symptoms for many years, with progressive loss of cognitive and functional abilities. In addition to the features of AD, described as amyloid plaques and neurofibrillary tangles, neuroinflammatory processes, genetic factors, and lifestyle also play important roles. Increasing evidence for lifestyle factors includes possible changes due to smoking, social engagement, and physical activity.

Methods: Morris water maze behavioral tasks were performed to analyze the formation of spatial memory. APPswe/PS1dE9 mice with a remarkable increase in amyloid-β production associated with certain behavioral abnormalities comparable to AD symptoms and age-matched wild-type littermates were trained several times at 3, 6, 9, and 12 months of age and compared with untrained groups at 9 and 12 months of age. Performance during the acquisition phase, in the reference memory test, and in searching strategies were analyzed.

Results: 9- and 12-month-old APP/PS1 mice showed cognitive impairment, especially in the reference memory test and searching strategies. This cognitive deterioration was reversed in 9- and 12-month-old APP/PS1 mice that had been previously trained several times. Even in the reversal test, in which memory formation must be adapted to the new platform position, several trained APP/PS1 mice performed better.

Conclusion: Repeated spatial memory training in the water maze showed positive effects on memory formation in APP/PS1 mice. Interestingly, the cohort that had been previously trained several times was able to use increased hippocampus-dependent strategies, similar to the WT mice. This may suggest that cognitively demanding and physically active tasks can improve cognitive function.