The endurance of medication overload: Rethinking the medication review process

Elderly mice with history of acetaminophen intoxication display worsened cognitive impairment and persistent elevation of astrocyte and microglia burden

“…First, frequent APAP intake can promote age-related deleterious effects in the brain and periphery 11 , 27 , 55 . Second, recurrent APAP exposure can occur starting at any age 3 , 14 , 38 , 39 , which is particularly concerning for elderly hosts due to compounding risk factors that include the increased susceptibility to overmedication 18 and the age-related impairment in hepatic and cerebral functions 19 , 20 . Thus, there is need for experimental efforts that query the neurological effects of recurrent APAP intoxication while accounting for yet evaluated, but translationally relevant parameters such as elderly subjects.…”

“…APAP intoxication can occur intentionally (suicide effort) or unintentionally (therapeutic misuse and/or unsupervised prolonged/frequent administration) 3,35,36 , which is notable because the latter type is also a key driver of the medication overload that plagues elderly populations 18,37 . In this sense, such individuals are at relevant risk of exposure to the metabolite and yet, to our knowledge, have not been evaluated in the context of associated cerebral abnormalities under experimental conditions.…”

“…The link between APAP and neurological impairments remains poorly understood, bolstering the growing concern over the metabolite’s enormous pharmaceutical prevalence and ease of access to populations that include the elderly 6 . It is important to highlight that elderly persons are at notable risk of the medication overload that elevates the likelihood of APAP exposure 18 , the compromised liver function that facilitates accumulation of toxic metabolites 19 , and the aging-associated disorders, such as Alzheimer’s disease (AD), that elevate the brain’s susceptibility to and severity of dyshomeostasis events 20 .…”

“…To our knowledge, experimental studies so far have examined rodent brains only up to adult life stages (typically, ≤ 6 months of age). And thus, there is desperate need to elucidate the neurological effects of APAP in elderly hosts, who are likely to be exposed since an earlier age 6 , 33 , 34 and correspond to the subgroup at highest risk of various relevant factors as noted earlier (APAP overexposure 18 , NAPQI accumulation 19 , and vulnerable to brain abnormalities 20 ).…”