Cognitive impairment after cancer treatment: mechanisms, clinical characterization, and management

Abstract

Cognitive impairment is a debilitating side effect experienced by patients with cancer treated with systemically administered anticancer therapies. With around 19.3 million new cases of cancer worldwide in 2020 and the five year survival rate growing from 50% in 1970 to 67% in 2013, an urgent need exists to understand enduring side effects with severe implications for quality of life. Whereas cognitive impairment associated with chemotherapy is recognized in patients with breast cancer, researchers have started to identify cognitive impairment associated with other treatments such as immune, endocrine, and targeted therapies only recently. The underlying mechanisms are diverse and therapy specific, so further evaluation is needed to develop effective therapeutic interventions. Drug and non-drug management strategies are emerging that target mechanistic pathways or the cognitive deficits themselves, but they need to be rigorously evaluated. Clinically, consistent use of objective diagnostic tools is necessary for accurate diagnosis and clinical characterization of cognitive impairment in patients treated with anticancer therapies. This should be supplemented with clinical guidelines that could be implemented in daily practice. This review summarizes the recent advances in the mechanisms, clinical characterization, and novel management strategies of cognitive impairment associated with treatment of non-central nervous system cancers.

Long‐term survivorship care after CAR‐T cell therapy

“…[40][41][42] However, it is unclear to what extent these heterogenous neuropsychiatric symptoms are attributable to CAR-T cell therapy versus the pre-existing burden of toxicities, mental health disorders, and cognitive difficulties associated with the underlying disease, comorbidities, and prior cancer treatment. 43 Reassuringly, recent studies incorporating longitudinal neuropsychological testing have concluded that most CAR-T cell recipients recover with no permanent neurocognitive deficits or with similar or only slight deterioration in neurocognitive performance compared to baseline. 39,44,45 Nevertheless, continued decline in perceived cognitive functioning has been reported by up to 25% of patients, particularly among those with severe ICANS or higher levels of baseline fatigue, anxiety, and depression.…”

“…Nevertheless, continued decline in perceived cognitive functioning has been reported by up to 25% of patients, particularly among those with severe ICANS or higher levels of baseline fatigue, anxiety, and depression 42 . Long‐term survivors of CAR‐T cell therapy may thus benefit from continued monitoring and support of neurocognitive health as they re‐integrate into their family and societal roles, including measures to promote physical activity, nutrition, sleep, and cognitive exercise 43 …”

“…In addition, persistent neurologic and/or psychiatric symptoms including mood disorders, cognitive impairment, cerebrovascular accidents, and neuropathy have been reported in 10%–48% of CAR‐T cell recipients for up to 1–5 years 40–42 . However, it is unclear to what extent these heterogenous neuropsychiatric symptoms are attributable to CAR‐T cell therapy versus the pre‐existing burden of toxicities, mental health disorders, and cognitive difficulties associated with the underlying disease, comorbidities, and prior cancer treatment 43 . Reassuringly, recent studies incorporating longitudinal neuropsychological testing have concluded that most CAR‐T cell recipients recover with no permanent neurocognitive deficits or with similar or only slight deterioration in neurocognitive performance compared to baseline 39,44,45 .…”

“…42 Long-term survivors of CAR-T cell therapy may thus benefit from continued monitoring and support of neurocognitive health as they re-integrate into their family and societal roles, including measures to promote physical activity, nutrition, sleep, and cognitive exercise. 43 Emerging forms of late-onset neurotoxicity have been identified…”

Progress in cancer neuroscience

“…174 Traditional cancer therapies, including chemotherapies and radiation, have long-lasting lethal impacts on nervous system activities, evident as cancer therapy-associated cognitive disruption (impaired memory, attention, multitasking, and sometimes enhanced anxiety) and as peripheral neuropathies (motor weakness, sensory loss, or pain). 174 Similar prolonged nervous system impact by novel targeted and cancer immune therapies require attention. Cancer therapies differentially influence cognition and the nerve types impacted in chemotherapy-induced peripheral neuropathy.…”