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Abstract
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.