Survival In Darkness: The Risk of Cancer Treatments in Dementia

As the average age of the population continues to rise, the prevalence of both cancer and dementia increases significantly, particularly among the elderly. This overlap presents a growing challenge for healthcare systems worldwide [1]. The relationship between these two diseases can be explored through various approaches, such as the incidence of cancer in patients with dementia [2], mortality risk in individuals with both conditions [3], or the influence of cancer on survivors and their subsequent risk of developing dementia [4].

The latter relationship can be likened to a “perspectivedependent sculpture,” where the observed connection varies significantly depending on the study design, methodology, and analytical approach. While some studies suggest a reduced risk of dementia among cancer survivors [5], others point to an increased risk and try to explain it [6]. Notably, a study involving twins, where one experienced cancer and the other did not, highlighted an elevated risk of dementia following cancer survival [7].

Amidst the ongoing debate over whether cancer survivors face an increased or decreased risk of dementia, this review aims to explore the impact of pharmacological interventions on posttreatment survivors. Our focus is to take a deeper look at how medications prescribed during and after cancer treatment influence cognitive outcomes in cancer survivals.

Cancer treatments can directly impact the risk of dementia through various pathways. For instance, chemotherapy is known to induce cognitive impairment, often referred to as “chemo brain” [8]. Studies have shown that certain chemotherapy agents, such as doxorubicin can induce this phenomenon [9]. Hormonal therapies, such as those used in breast cancer or androgen deprivation therapy for prostate cancer, have also been linked to an increased risk of dementia due to their influence on hormone levels, which play a critical role in cognitive function [10].

In the case of radiation therapy, used for brain tumors or brain metastases, there is a significant risk of direct damage to neural integrity. This treatment can induce vascular damage, neuroinflammation, and disruption of the blood-brain barrier, all of which can contribute to cognitive dysfunction and potentially predispose survivors to dementia [11]. In addition, novel therapies, including immunotherapy, have revolutionized cancer treatment but may also pose neurocognitive risks. While data on these therapies are limited, case studies have reported cognitive side effects, such as confusion and memory deficits, necessitating further investigation into their long-term effects on the brain [12].

A cancer diagnosis and its treatment often result in significant psychological distress, including anxiety, depression, and posttraumatic stress disorder (PTSD) [13]. Mitchell et al. conducted a meta-analysis encompassing over 70 international studies and more than 10,000 cancer patients and revealed that depression, adjustment disorders and anxiety disorders were observed in 38.2% of this population [14]. Persistent psychological distress can accelerate cognitive decline, as depression and chronic stress are well-established risk factors for dementia [15].

Oncologists are among the primary prescribers of psychotropic medications to manage psychological distress in cancer patients [16]. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are frequently used to alleviate depressive symptoms; however, various other psychotropic drugs, including selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and benzodiazepines, are also commonly prescribed not only for psychological distress but also to manage cancer-related symptoms and treatment side effects [16]. While SSRIs are generally considered safer, TCAs [17], due to their anticholinergic properties, have been associated with cognitive decline, and prolonged benzodiazepine use has been linked to an increased risk of dementia, especially in older adults [18]. Given the growing population of cancer survivors, the role of psychotropic medications in long-term cognitive health must be carefully considered. Striking a balance between managing psychological disorders and mitigating the risk of cognitive dysfunction, such as dementia, is essential to ensuring both the quality and longevity of survival in cancer patients. Future studies must integrate psychotropic medication as a key factor in understanding dementia risk among cancer survivors.

Cancer survivorship extends beyond achieving remission; it must encompass a holistic approach that ensures a high quality of life. The intricate relationship between cancer treatments, psychological distress, and dementia risk necessitates comprehensive strategies to mitigate cognitive decline in survivors. Both the direct effects of cancer therapies-such as chemotherapy, hormonal treatments, and radiation-and the indirect impact of psychological distress and psychotropic medications contribute to the complexity of this issue.

To safeguard cognitive health, long-term, large-scale studies are crucial to elucidate the underlying mechanisms and refine treatment protocols that minimize neurocognitive risks. Until these relationships are fully understood, proactive measures-including routine cognitive assessments, neuropsychological evaluations, and multidisciplinary survivorship care-must be prioritized. By addressing both physical and cognitive well-being, healthcare providers can ensure that cancer survivors not only live longer but also lead meaningful, fulfilling lives post-treatment.

We would like to declare that we used AI to assist with text improvement and editing.

None.

No conflict of interest.

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