Early Cognitive Training Rescues Remote Spatial Memory but Reduces Cognitive Flexibility in Alzheimer’s Disease Mice

Abstract

Background: Spatial memory dysfunction has been demonstrated in mouse models of Alzheimer's disease (AD) which is consistent with the clinical finding that the early signature of AD includes difficulties in the formation and/or storage of a memory. A stored memory-a long term memory-can be modulated via process called as memory retrieval that can either lead toward memory reconsolidation or even memory extinction. Objective: We aim to shed light on the fate of the spatial memory during memory reactivation and memory extinction using a water maze task. Methods: In Setup I, we trained 3-month-old mice (wild-type mice and mice with cerebral ␤-amyloidosis) and assessed the fate of remote memory after four months of retention interval (RI). In Setup II, we performed an early-extensive training at 2 months of age, retrained the same mice at 3 months of age, introduced four months of RI, and finally assessed remote spatial memory at 7 months of age. Results: We find in ␤-amyloidosis mice that memory reactivation problems were detectable at 7 months of age and were alleviated by cognitive overtraining. Similarly, forgetting of remote spatial memory was also minimized by cognitive overtraining. Finally, we show that the cognitive training facilitates the recovery of the reactivated spatial memory while reducing the ability to form new spatial memory in AD mice. Conclusion: This result may explain the rationality behind the cognitive reserve observed in AD patients and elderly with severe ␤-amyloidosis not corresponding to the actual low dementia symptoms.

Detection and Prediction of Mild Cognitive Impairment in Alzheimer’s Disease Mice

“…Finally, we used a simple logistic regression algorithm as a tool for predictive analysis of a mouse into APPtg or APPwt. Because of small animal size (total 49 mice), some animals had to be included in this study from a previous study (9 APPwt and 10 APPtg were also included in this data analysis from Set-up I experiment [ 15 ]). Again, we used repeated k-folds cross-validation on training datasets to handle small datasets.…”

“…The number of animals in each group are summarized in Table 1 . Importantly, nine APPwt and ten APPtg mcie were also included in the data analysis of 1 min ITI groups from Set-up I experiment of [ 15 ].…”

“…A spatial intensity is a function of the spatial location [ 23 ]. The point pattern map of mice trajectories was previously applied in similar experiments and details can be found elsewhere [ 15, 23 ].…”

“…The average WM performance was assessed for each mouse per day. The statistical evaluation was performed using a linear mixed model for repeated measures longitudinal data [15,18] in which proximity is a function of day and group. A day was considered a categorical variable and an animal's variation was considered a random effect.…”

“…However, the cognitive loss in this animal model was reported to be detectable only from 6.5 months of age in the water maze task [ 14 ], months after the first Aβ deposition in the hippocampus. Recently, we reported that early cognitive training rescues remote spatial memory but reduces cognitive flexibility in this model [ 15 ].…”