The Biological Intersection Between Chemotherapy-Related Cognitive Impairment and Alzheimer Disease

Abstract

Alzheimer disease (AD) is the most common type of dementia and one of the leading causes of death in elderly patients. The number of patients with AD in the United States is projected to double by 2060. Thus, understanding modifiable risk factors for AD is an urgent public health priority. In parallel with the number of patients with AD, the number of cancer survivors is estimated to increase significantly, and up to 80% of cancer patients treated with chemotherapy will develop cognitive deficits, termed chemotherapy-related cognitive impairment. This review discusses biologically plausible pathways underlying both disorders, with the goal of understanding why a proportion of chemotherapy patients may be at higher risk of developing AD. Highlighted are the E4 allele of the apolipoprotein E gene, neuroinflammation, oxidative stress, DNA damage, mitochondrial dysfunction, neuronal and synaptic loss, cellular senescence, brain-derived neurotrophic factor signaling, white matter damage, blood–brain barrier/vascular dysfunction, tau pathology, and transposable element reactivation.