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Alzheimer's disease (AD) has traditionally been considered solely a neurological condition. Therefore, numerous studies have been conducted to identify the existence of pathophysiological changes affecting the brain and the blood-brain barrier in individuals with AD. Such studies have provided invaluable insight into possible changes to the central nervous system exposure of drugs prescribed to individuals with AD. However, there is now increasing recognition that extra-neurological systems may also be affected in AD, such as the small intestine, liver, and kidneys. Examination of these peripheral pathophysiological changes is now a burgeoning area of scientific research, owing to the potential impact of these changes on the absorption, distribution, metabolism, and excretion (ADME) of drugs used for both AD and other concomitant conditions in this population. The purpose of this review is to identify and summarise available literature reporting alterations to key organs influencing the pharmacokinetics of drugs, with any changes to the small intestine, liver, kidney, and circulatory system on the ADME of drugs described. By assessing studies in both rodent models of AD and samples from humans with AD, this review highlights possible dosage adjustment requirements for both AD and non-AD drugs so as to ensure the achievement of optimum pharmacotherapy in individuals with AD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Older people are at a greater risk of medicine-induced toxicity resulting from either increased drug sensitivity or age-related pharmacokinetic changes. The scenario is further complicated with the two most prevalent age-related neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). With aging, AD and PD, there is growing evidence of altered structure and function of the blood-brain barrier (BBB), including modifications to tight junctions and efflux transporters, such as P-glycoprotein. The subsequent impact on CNS drug exposure and risk of neurotoxicity from systemically-acting medicines is less well characterized. The purpose of this review, therefore, is to provide an overview of the multiple changes that occur to the BBB as a result of aging, AD and PD, and the impact that such changes have on CNS exposure of drugs, based on studies conducted in aged rodents or rodent models of disease, and in elderly people with and without AD or PD., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)