Neurological aging and cancer

Abstract

The effects of aging on the nervous system are widespread and come from changes on molecules, cells, vasculature, and gross morphology. The changes in the brain include decrease in volume, gray matter thinning, abnormalities in proteostasis, apparition of white matter lesions, nerve cell death, dendritic retraction and expansion, synapse loss and remodeling, and glial cell (astrocytes and microglia) reactivity. There are also changes in the autonomous and peripheral nervous system, such as lower sensibility of adrenergic receptors and lower recovery of function after peripheral nerve damage. The mentioned changes can have an impact in the functionality of the person. In general, said impact of these changes on a person’s functionality is discrete, but combined with other environmental factors such as vascular disease, diabetes, or cancer, it can lead the individual to true impairment. Altogether, even without a disease, these changes put the older individual at higher risk of neurotoxic effects of chemotherapy, such as encephalopathy, neuropathy, and cognitive decline. The risk of developing neurotoxicity is dependent on numerous factors, including dose intensity, baseline neurological deficits, drug interactions, and drug mechanism of action. Early recognition of adverse neurologic effects and differentiation from central nervous system progression of cancer is critical for timely and appropriate adjustments in dosing or discontinuation of the drug, in order to protect the functionality and independence of the older patient with cancer.