Cognitive Flexibility as a Possible Index of Age-Related Cognitive Decline

Background Cognitive flexibility declines with age, disruptions are often observed in patients with dementia, including those with Alzheimer’s disease (AD), particularly in the early stages. In mice, we have recently reported that probiotic treatment with a mixture of Bifidobacterium animalis subsp. lactis LKM512 and arginine improved cognitive flexibility in young and middle-aged adult mice, by using originally developed behavioral task, indicating that probiotic treatment has a potential to prevent the aged-dependent cognitive decline and the onset of dementia. Aims & Objectives The aim of this study is to confirm cognitive flexibility can be a good index for the early symptom of dementia, and progress good test method for cognitive flexibility in human. In mice study, cognitive flexibility of AD model mice was assessed. In human preclinical study, we assessed aged dependent cognitive decline of paired-associate memory in which we suspect to reflect cognitive flexibility. Method In mice, cognitive flexibility was assessed using our established behavioral task paradigm in an IntelliCage system with the second-generation AD mouse model, AppNL-G-F mice. In human, we developed a Japanese modified version App of the FNAME test, originally developed by Dr. Rentz and co-workers (2011) which assesses face and name associative memory, and assessed in young, middle-aged and aged Japanese people. Results In mice study, older AppNL-G-F mice (14 months of age) were found to exhibit cognitive inflexibility, despite demonstrating comparable performance to that of control mice in spatial learning and behavioral sequencing learning tasks. In human study, we found age-dependent decrease in the score. Discussion & Conclusions The AD model mice showed cognitive inflexibility even at the time when they showed normal spatial memory ability, indicating that cognitive flexibility can be a good index at least in mice. In human, we found that the age-dependent decline in scores of the FNAME test, indicating that FNAME test can be a good index of the age-dependent cognitive decline. Further discussion and studies are needed to improve test methods in huma in terms of similarity and differences in task between mice and human.