Lifestyle factors may affect mental health and play a critical role in the development of neurodegenerative diseases including Alzheimer’s disease(AD).However,whether the temperatures of daily beverages have any impact on cognitive function and AD development has never been studied.In this study,we investigated the effects of daily drinking water temperatures on cognitive function and AD development and progression in mice and the underlying mechanisms.Cognitive function of mice was assessed using passive avoidance test,open field test,and Morris water maze.Wild-type Kunming mice receiving intragastric water(IW,10 mL/kg,2 times/day)at 0℃ for consecutive 15 days displayed significant cognitive defects accompanied by significant decrease in gain of body weight,gastric emptying rate,pepsin activity,and an increase in the energy charge in the cortex when compared with mice receiving the same amount of IW at 25 ℃(a temperature mimicking most common drinking habits in human),suggesting the altered neuroenergetics may cause cognitive decline.Similarly,in the transgenic APPwse/PS1De9 familial AD mice and their age-and gender-matched wild-type C57BL/6 mice,receiving IW at 0 ℃,but not at 25 ℃,for 35 days caused a significant time-dependent decrease in body weight and cognitive function,accompanied by a decreased expression of PI3K,Akt,the glutamate/GABA ratio,as well as neuropathy with significant amyloid lesion in the cortex and hippocampus.All of these changes were significantly aggravated in the APPwse/PS1De9 mice than in the control C57BL/6 mice.These data demonstrate that daily beverage at 0℃ may alter brain insulin-mediated neuroenergetics,glutamate/GABA ratio,cause cognitive decline and neuropathy,and promote AD progression.