General and Supportive Care
Cognitive dysfunctions in elderly cancer patients: A new challenge for oncologists

https://doi.org/10.1016/j.ctrv.2014.03.003Get rights and content

Abstract

While chemotherapy is more commonly proposed to the elderly population with cancer, little is known about the impact of therapy on cognitive functions and the way of managing such dysfunctions in clinical practice among this population. Aging by itself is associated with cognitive modifications, comorbidities and functional decline, which may have a significant impact on the autonomy. In elderly patients with cancer, several factors like the biologic processes underlying the disease and therapies will contribute to favor the cognitive decline. The chemobrain phenomenon, referring to the chemotherapy-induced impairment of memory, executive function or information processing speed has been extensively described in patients with breast cancer, and the few studies available in older patients suggest that the impact could be more pronounced in patients with pre-existing troubles.

Because cognitive dysfunction may impact the quality of life as well as compliance to treatment, assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice as it should influence the choice of the most appropriate therapy, including oral drugs. In that respect, geriatric assessment in oncology should include more sensitive screening tests than Mini Mental State Examination (MMSE) and if needed they have to be completed with a more detailed assessment of subtle disorders.

Introduction

Due to the overall increase in life expectancy coupled with a more appropriate therapeutic management, elderly cancer patients are expected to live longer and in better conditions [1]. The prognosis among this population has been particularly improved because of the possibility of curative treatments through various modalities (surgery, radiotherapy, chemotherapy and targeted therapies). The indications of adjuvant chemotherapy after surgery are becoming wider and age is no longer a limiting parameter. Furthermore, treatments of advanced disease, like palliative chemotherapy, are more frequently proposed to elderly. Nevertheless, older adults are poorly represented in most oncology clinical trials and only a small number of studies have focused on patients of advanced biological age, so clinical results are extrapolated to elderly.

Aging often correlates with frailty and the toxicity of antitumoral agents is a major issue in elderly patients [2]. Among these side-effects, difficulty with memory, attention and concentration defined as “chemobrain” [3], in reference to chemotherapy-induced cognitive impairments, has been particularly studied among middle aged and women treated with chemotherapy for breast cancer. These cognitive impairments have been shown to be moderate and most often transient, but they can sometimes persist for several years after the end of therapy [4]. Nevertheless, cytotoxic drugs are not the only factors involved in the occurrence of cognitive dysfunction. Indeed, hormone therapies could be associated with increased risk of cognitive changes in some breast cancer patients [5] and among men undergoing androgen deprivation treatment for prostate cancer [6]. Furthermore, postoperative dysfunctions, psychological distress related to the announcement of diagnosis, fatigue and genetic factors could be involved. The biological adverse effects of cancer itself, know as the cancerbrain concept, could also play a role through increased inflammation, dysregulation of cytokines or oxidative stresses, which notably suggests the impact of cancer itself on cognitive functions [7], [8], [9], [10], [11].

The impact of cancer and chemotherapy on cognitive functioning and quality of life is supposed to depend on various factors including baseline cognitive functions, which are expected to be reduced in older compared with younger patients. Yet, little is known regarding the effect of treatment on the older patient’s cognition [12] and whether chemotherapy-associated cognitive changes affects the older patient’s ability to perform daily activities required to maintain functional independence or not.

Aging by itself is associated with some cognitive dysfunctions, comorbidities and functional decline, which may have a significant impact on the patient’s autonomy. Those alterations are expected to be enhanced by cancer, so initial cognitive status could influence the choice of treatment and the modality of administration. Treatments also influence the functional status and functional decline is associated with a worse prognosis. Additionally, elderly population is characterized by an increased consumption of medications, which may further contribute to impact adherence to cancer treatment.

The aim of this paper is to present a state of the art regarding cancer-induced cognitive impairment in elderly patients, and to propose assessment tools adapted to this population in clinical routine. Studies including batteries of neuropsychological tests are discussed from a systematic review of the literature. This review was based on medline-indexed articles including ‘cancer’, ‘elderly’ and ‘cognition’ as keywords in the title or the abstract, and published in the past decade. The aim is to define the role of age as a risk factor per se, the impact of cancer treatments on cognition by considering explanatory mechanisms and the possible consequences on quality of life and adherence to treatment. Finally, some recommendations are given regarding the evaluation of cognitive assessment in older cancer patients and the feasibility of its management in practice.

Section snippets

Cognition, depression and cognitive reserve

Elderly people are particularly at risk to develop cognitive decline that may sometimes degenerate into true dementia symptoms. In normal aging, many effects of age have been demonstrated on cognitive functioning like a slowdown in processing speed [13], a reduced efficiency of inhibitory control (mechanisms preventing non-relevant information from interfering with current task) and a decrease in performance related to working memory (responsible for temporary maintenance and manipulation of

Dementia risk in patients with cancer

The increasing rate of comorbidity with age [24] may affect life expectancy, risk of subsequent functional decline and the development of cognitive impairment or dementia. Dementia criteria are based on multiple cognitive deficits, with significant impact in social or occupational functioning, resulting in a significant decline from a previous level of functioning, with a gradual onset and a continuing cognitive decline. These impairments may not be due to other central nervous system

Impact of cancer treatments on cognition in elderly

While chemotherapy is expected to induce a long-term risk of dementia syndrome, early troubles specific to some cognitive domains may be observed. In that respect, chemobrain refers to impairments of episodic memory, working memory, executive functions, attention and information processing speed [32], [33], [34], and recent neuroimaging studies revealed a fronto-subcortical effect of chemotherapy [35], [36], [37], [38]. In practice, patients experience difficulties regarding memory information

Cognitive evaluation in elderly cancer patients and recommendations regarding assessment

Oncogeriatric assessment, which could be proposed to patients over 70 years, aims to screen frail patients. A number of epidemiological studies performed outside the field of oncology have reported that frailty increased the risk of future cognitive decline and that cognitive impairment increased the risk of frailty, suggesting that cognition and frailty interact within a cycle of decline associated with ageing [75]. In geriatric oncology, a diagnosis of cognitive impairment may also alter

Conclusion

Aging is associated with some cognitive modifications, comorbidities and functional decline which, in case of large deficits, may have an impact on the autonomy. There is a growing body of evidence that cancer therapy may impact cognitive function, but few studies have focused on older adults [100]. Nevertheless, the results available suggest that elderly cancer patients would be at greater risk for increased age-related brain changes and also of dementia secondary to cancer and cancer

Conflict of interest statement

The authors have declared no conflicts of interest.

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