Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation

Abstract

PURPOSE To use functional magnetic resonance imaging (fMRI) to prospectively examine pre-treatment predictors of post-treatment fatigue and cognitive dysfunction in women treated with adjuvant chemotherapy for breast cancer. Fatigue and cognitive dysfunction often co-occur in women treated for breast cancer. We hypothesized that pre-treatment factors, unrelated to chemotherapy per se, might increase vulnerability to post-treatment fatigue and cognitive dysfunction. METHODS Patients treated with (n=28) or without chemotherapy (n=37) and healthy controls (n=32) were scanned coincident with pre- and one-month-post-chemotherapy during a verbal working memory task (VWMT) and assessed for fatigue, worry, and cognitive dysfunction. fMRI activity measures in the frontoparietal executive network were used in multiple linear regression to predict post-treatment fatigue and cognitive function. RESULTS The chemotherapy group reported greater pre-treatment fatigue than controls and showed compromised neural response characterized by higher spatial variance in executive network activity than the non-chemotherapy group. Also, the chemotherapy group reported greater post-treatment fatigue than the other groups. Linear regression indicated that pre-treatment spatial variance in executive network activation predicted post-treatment fatigue severity and cognitive complaints, while treatment group, age, hemoglobin, worry, and mean executive network activity levels did not predict these outcomes. CONCLUSIONS Pre-treatment neural inefficiency (indexed by high spatial variance) in the executive network, which supports attention and working memory, was a better predictor of post-treatment cognitive and fatigue complaints than exposure to chemotherapy per se. This executive network compromise could be a pre-treatment neuromarker of risk, indicating patients most likely to benefit from early intervention for fatigue and cognitive dysfunction.

Association of Fatigue Intensification with Cognitive Impairment during Radiation Therapy for Prostate Cancer

“…The previous lit erature has mostly focused on cognitive impairment in fatigued cancer patients after receiving chemotherapy or adjuvant therapy [9, 11, 12]. For example, cancer survivors often report posttreatment cognitive difficulties which tend to be diffuse in the domains of attention, concentration, verbal and visual memories, as well as processing speed, and working memory [8, 11, 13]. In addition, fatigue, cognitive impairment, and depression often co-occur in cancer patients after receiving chemotherapy, possibly due to chemotherapeutic agent-related systemic toxicity as well as direct neurotoxicity [13-15].…”

Mulheres Submetidas à Quimioterapia e suas Funções Cognitivas

“…A maioria dos estudos explorou, além das funções executivas, outros domínios cognitivos e sintomas concomitantes ao processo da avaliação (Ando-Tanabe, 2014, Askren et al, 2014Chen et al, 2013;Dumas, 2013;Ganz et al, 2003;Jansen, 2011;Kam et al, 2016;Kesler et al, 2011;Koppelmans et al, 2012;Lyon et al, 2016;McDonald et al, 2013;Miao et al, 2016;Park et al, 2015;Piccirillo, et al, 2015;Yao et al, 2016;Zheng et al, 2014). Apenas Kam et al (2016), Miao et al (2016) e McDonald et al (2013) delimitaram-se à investigação e discussão aos aspectos relevantes do funcionamento executivo.…”

“…Corroborando com esses dados, Askren et al (2014), Dumas (2013), Kam et al (2016), Kesler (2011;, Miao et al (2016), McDonald et al (2013) e Piccirillo et al (2015, ao examinarem imagens de ressonância magnética, observaram alterações em ligações funcionais nas redes cerebrais no que se refere à função executiva.…”

“…E, embora a avaliação neuropsicológica não tenha o propósito de conhecer qualquer tipo de função pura- Poucos artigos encontrados nessa revisão dedicaram-se à avaliação neuropsicológica para investigação exclusiva de aspectos das funções executivas (Kam et al, 2016, Miao et al, 2016, McDonald et al, 2013. Como demonstrado, a grande maioria apenas limita-se ao exame de poucos aspectos associados ao funcionamento executivo, o que pode limitar o rastreio das funções executivas, demonstrando uma necessidade por maior aprofundamento do tema (Lyon et al, 2016;Yao et al, 2016;Park et al, 2015;Zheng et al, 2014;Ganz et al, 2003;Chen X et al, 2014;Koppelmans, 2012;Piccirillo, et al, 2015;Askren et al, 2014;Dumas, 2013;Kesler, 2013;Kesler et al, 2011;Ando-Tanabe, 2014, Chen et al, 2013, Jansen, 2011. Esses estudos, apesar de avaliarem uma diversidade de domínios cognitivos, foram selecionados nesse trabalho por incluíremem instrumentos de avaliação de subdomínios das funções executivas podendo fornecer informações -não menos importantes -sobre o impacto da quimioterapia em pacientes com câncer de mama.…”

“…Algumas pesquisas levantadas destacaram determinadas alterações do funcionamento executivo as quais tiveram relação significativa direta entre comorbidades como fadiga (Askren et al, 2014), depressão (Ando-Tanabe, 2014; Ganz et al, 2003) e outras condições como recebimento da terapia hormonal (Ganz et al, 2003). Todavia, a correlação com a depressão somente não foi corroborada por Koppelmans (2012).…”