Acarbose improves cognitive function in a mouse model of normal aging but not Alzheimer's disease

Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSDeclines in function occur in both "normal" aging (in the absence of disease) and age-related pathological contexts, like Alzheimers disease (AD). Whether "anti-aging" interventions (that extend lifespan) also promote cognitive function in aging and AD remains unexplored. METHODSWe assessed the effect of acarbose (1000 ppm from 4 months of age) on spatial learning and memory using the Morris water maze in young adult (6 mo), mid-aged (12 mo), or aged (24 mo) cohorts of normal aging (Ntg-HET3) and AD-relevant (5xFAD-HET3) genetically heterogeneous mice. RESULTSIn mid-aged and aged Ntg-HET3 mice, acarbose treatment resulted in performance equivalent to young adults. Conversely, acarbose failed to ameliorate age-related deficits in 5xFAD-HET3 mice. DISCUSSIONThis work demonstrates that anti-aging interventions can also promote cognitive longevity in normal aging. Further, it reinforces that AD is not simply accelerated aging and requires therapies beyond anti-aging interventions that target its unique molecular and cellular drivers.