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Tumor Discovery The mechanism of cancer-related cognitive decline

(MCI) and dementia were as high as 15.5% and 6.0%, establishes a link with the central nervous system (CNS)
respectively . With the continuous improvements in in the pathological process of eliciting cognitive decline
[2]
cancer diagnosis and treatment, the mortality rate has and psychobehavioral abnormalities. Therefore, this article
declined significantly; the total cancer mortality rate aims to summarize the research results published in the
declined by 27% from 1991 to 2016, and those for men and recent decade, reviews, and collates the research progresses
women declined annually by 1.8% and 1.4%, respectively, on the potential pathogenesis of CRCI, and provides
[3]
from 2007 to 2016 . Nonetheless, the increase in the life ideas for exploring early intervention and comprehensive
span of cancer patients is accompanied by the increased management strategies.
rates of sequelae and adverse reactions associated with
cancer and its treatment. Since 1990s, several studies 2. Direct neurotoxic effects of cancer
have confirmed the existence of cancer-related cognitive
impairment (CRCI) [4,5] . Cognitive impairment can 2.1. Immunoinflammatory response
occur at any stages of cancer, especially during and after Recent studies have shown that the patients with hemato-
chemotherapy, which seriously affects the quality of life logic malignancies and breast cancer experienced cognitive
and functional independence of patients and heavily decline prior to receiving any adjuvant therapy [13,14] .
burdens their families and the society . At present, CRCI Cross-sectional studies revealed that magnetic resonance
[6]
mainly refers to impairment in the cognitive domains of imaging of patients with breast cancer and several other
the short-term and working memory, attention, executive types of systemic cancers, with or without chemotherapy,
functions, and/or processing speed in the patients with showed significant reduction in the cortical surface area
systemic cancer following chemotherapy . A nationwide or thickness of multiple brain regions . These studies
[7]
[15]
prospective cohort study in China showed that the suggested that cancer might have some biological impacts
incidence of cognitive impairment within 6 months after on the cognitive function. The tumor microenvironment
chemotherapy in breast cancer patients was significantly (TME) is a complex network comprising tumor cells, tissue
higher than that in age-matched non-cancer patients, stroma, and infiltrating immune cells. All of these can
which might be associated with anxiety, depression, and produce inflammatory factors, mainly interleukin (IL)-6,
reduced cognitive reserve at baseline (pre-chemotherapy) IL-1β, IL-2, IL-8, IL-17, TNF-α, and granulocyte colony-
[8] . It is also reported that 30 – 40% of cancer patients stimulating factor (CSF) . Analysis of the inflammatory
[16]
have CRCI before treatment, up to 75% may experience markers in 174 newly diagnosed breast cancer patients
cognitive decline during chemotherapy, and 60% may revealed significant elevated levels of serum IL-1 receptor
experience cognitive decline after adjuvant therapy [6,9] . antagonist as compared to the control participants without
This suggests that both cancer and its adjuvant therapy cancer (88 cases) . A longitudinal cohort study showed
[17]
may affect the cognitive function of patients. that the levels of 17 cytokines in 75 early-stage breast
Despite evidence of the existence and adverse effects cancer patients who were on chemotherapy at that time
of CRCI, the underlying biological mechanisms remain fluctuated over the period of 24 months, and the alterations
poorly understood. Moreover, it is unclear whether were associated with specific cognitive domains. This
cognitive decline is caused exclusively by cancer, its association reveals that prototypical cytokines, such as
treatment, or psychological factors. A systematic review IL-6, TNF-α, and IL-1β, as well as cytokines from multiple
revealed that chemotherapeutic drugs induce the classes may contribute to the inflammatory environment
[18]
production of superoxide radicals in the peripheral blood related to cognitive impairment . The cancer itself and its
that oxidatively modify apolipoprotein A1. Apolipoprotein microenvironment can produce inflammatory factors due
A1 elevates the pro-inflammatory tumor necrosis factor to local oxidative stressor environmental stimuli. These
alpha (TNF-α) levels in the peripheral blood, which inflammatory factors enter the brain tissue by directly
induces oxidative stress in brain parenchyma through crossing the blood-brain barrier (BBB) or through the
multiple pathways, thereby inducing apoptosis and highly permeable capillaries of the circumventricular
affecting the cognitive function [10,11] . It is also known organs (CVOs) . They activate the glial cells, thus inducing
[19]
that reactive oxygen species-mediated oxidative stress pro-inflammatory signaling cascade or directly interfering
in the brain tissue is one of the important pathogenic with important neuronal circuits [20-22] . Consequently,
mechanisms of Alzheimer’s disease (AD), suggesting that the homeostasis and cognitive function are affected,
it could be the underlying pathophysiological mechanism thereby establishing a link with the CNS. Moreover,
of CRCI. However, some studies have demonstrated the inflammatory factors activate the macrophages and
that the sources of oxidative stress are not identical in dendritic cells in and around the blood vessels of the
these two diseases . It is unclear how systemic cancer choroid plexus and meninges before entering the brain
[12]

Volume 1 Issue 1 (2022) 2 https://doi.org/10.36922/td.v1i1.46