Abstract

With the aging population rapidly increasing worldwide, preventive measures and treatments for age-related cognitive decline and dementia are of utmost importance. We have previously demonstrated that the consumption of iso-α-acids (IAA), which are hop-derived bitter compounds in beer, prevents the formation of disease pathology in a transgenic mouse model of Alzheimer’s disease (AD). However, the effect of IAA consumption on age-related cognitive decline is unknown. In the present study, we examined the effect of long-term and short-term dietary consumption of IAA, on age-related memory impairments and inflammation in the hippocampus of aged mice. When compared with young mice, aged mice showed impairment in spatial working memory during the Y-maze spontaneous alternation test, impairment in object recognition memory during the novel object recognition test (NORT), a pro-inflammatory hippocampal microglial phenotype with increased CD86 expression and inflammatory cytokine production, increased levels of glutamate and amyloid β1–42, and decreased levels of dopamine (DA). In aged mice fed IAA for 3 months, the age-related alterations in memory, microglial inflammation, and glutamate, amyloid β1–42, and DA levels were all significantly attenuated. Additionally, the oral administration of IAA for 7 days in aged mice with memory impairment, also improved spatial and object recognition memory. These results suggest that IAA consumption prevents inflammation in the hippocampus and ameliorates age-related cognitive decline.

Highlights

  • The increasing burden of dementia and cognitive impairment in rapidly expanding aging populations is shouldered by patients and their families and by national healthcare systems

  • Our study demonstrated that the consumption of IAA reduced inflammation in the brain and prevented the cognitive impairment associated with normal aging in mice

  • Aged mice displayed microglial inflammation in the hippocampus and impairments in spatial working memory and object recognition memory; but both the inflammation and the cognitive impairments were reduced by long-term dietary administration of IAA

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Summary

Introduction

The increasing burden of dementia and cognitive impairment in rapidly expanding aging populations is shouldered by patients and their families and by national healthcare systems. Etiological studies on lifestyle suggest that low to moderate consumption of alcohol, such as wine and beer, may reduce the risk of cognitive decline and the development of dementia. Iso-α-acids Attenuate Age-Related Cognitive Decline risk of developing a neurodegenerative disease than those who either abstained from alcoholic beverages or drank heavily (Matsui et al, 2011; Neafsey and Collins, 2011; Horvat et al, 2015). These risk-reducing effects are thought to be because of the profile of compounds found in alcoholic beverages. Beer has remained the most-consumed alcoholic beverage in the world for more than a thousand years; to date there are few reports on which constituents of beer could be beneficial for preventing cognitive decline

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