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An improved understanding of the interaction of cerebrovascular damage with AD is crucial for the development of therapeutic approaches. Herein, we investigated the effects of chronic cerebral hypoperfusion (CCH) in a 5XFAD transgenic (Tg) mouse model of AD. We established CCH conditions in both Tg and non-Tg mice by inducing unilateral common carotid artery occlusion (UCCAO). Cognitive performance in mice was evaluated, and their brain tissue was examined for amyloid-beta (A\u03b2) pathology to elucidate possible mechanisms. We found that UCCAO-operated Tg mice showed impaired cognitive flexibility in the reversal phase of the hidden-platform water maze task compared to sham-operated Tg mice. Interestingly, UCCAO-operated Tg mice used fewer spatial cognitive strategies than sham-operated Tg mice during reversal learning. These cognitive deficits were accompanied by increased A\u03b2 plaque burden and A\u03b242 levels in the hippocampus and prefrontal cortex, 2 regions that play essential roles in the regulation of cognitive flexibility. Furthermore, changes in cognitive flexibility are strongly correlated with the expression levels of enzymes related to A\u03b2 clearance, such as neprilysin and insulin-degrading enzymes. These findings suggest that, in 5XFAD mice, impaired cognitive flexibility is related to CCH, and that A\u03b2 clearance might be involved in this process.<\/jats:p>","DOI":"10.1093\/gerona\/glab075","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T06:19:21Z","timestamp":1615529961000},"page":"1169-1178","source":"Crossref","is-referenced-by-count":16,"title":["Impaired Cognitive Flexibility Induced by Chronic Cerebral Hypoperfusion in the 5XFAD Transgenic Mouse Model of Mixed Dementia"],"prefix":"10.1093","volume":"76","author":[{"given":"Min-Soo","family":"Kim","sequence":"first","affiliation":[{"name":"Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea"},{"name":"Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul, South 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