title: Cognitive Function in Patients With Colorectal Cancer Who Do and Do Not Receive Chemotherapy: A Prospective, Longitudinal, Controlled Study.
abstract: OBJECTIVE
  Cognitive dysfunction is reported in people with cancer. Therefore, we evaluated longitudinal changes in cognitive function and underlying mechanisms in people with colorectal cancer (CRC) and healthy controls (HCs).
  
  
  METHODS
  Participants completed cognitive assessments and questionnaires reporting cognitive symptoms, fatigue, quality of life, and anxiety/depression at baseline (before chemotherapy, if given) and 6, 12, and 24 months. Blood tests included cytokines, clotting factors, apolipoprotein E genotype, and sex hormones. Primary end point was overall cognitive function measured by the Global Deficit Score at 12 months.
  
  
  RESULTS
  We recruited 289 patients with localized CRC (173 received chemotherapy; median age, 59 years; 63% male), 73 patients with limited metastatic/recurrent CRC, and 72 HCs. Cognitive impairment was more frequent in patients with localized CRC than HCs at baseline (43% v 15%, respectively; P < .001) and 12 months (46% v 13%, respectively; P < .001), with no significant effect of chemotherapy. Attention/working memory, verbal learning/memory, and complex processing speed were most affected. Cognitive impairment was similar in patients with localized and metastatic CRC. Cytokine levels were elevated in patients with CRC compared with HCs. There was no association between overall cognitive function and fatigue, quality of life, anxiety/depression, or any blood test. Cognitive symptoms at 12 months were reported in 25% of patients with localized CRC versus 17% of HCs (P = .19). More participants who received chemotherapy had cognitive symptoms at 6 months (32%) versus those who did not (16%; P = .007), with no significant difference at 12 months (29% v 21%, respectively; P = .19). Objective cognitive function was only weakly associated with cognitive symptoms.
  
  
  CONCLUSIONS
  Patients with CRC had substantially more cognitive impairment at every assessment than HCs, with no significant added effect of chemotherapy. Mechanisms of cognitive impairment remain unknown.
authors.affiliation: Janette L. Vardy, Haryana M. Dhillon, Corrinne Renton, and Stephen Clarke, University of Sydney; Janette L. Vardy and Philip Beale, Concord Cancer Centre, Sydney, New South Wales, Australia; Janette L. Vardy, Anna Dodd, and Ian F. Tannock, Princess Margaret Cancer Centre, University of Toronto; Sean B. Rourke, Tsegaye Bekele, and Haibo Zhang, St Michael's Hospital, University of Toronto, Toronto; and Gregory R. Pond, McMaster University, Hamilton, Ontario, Canada. janette.vardy@sydney.edu.au.
authors.forename: Janette L
authors.initials: JL
authors.lastname: Vardy
authors.affiliation: Janette L. Vardy, Haryana M. Dhillon, Corrinne Renton, and Stephen Clarke, University of Sydney; Janette L. Vardy and Philip Beale, Concord Cancer Centre, Sydney, New South Wales, Australia; Janette L. Vardy, Anna Dodd, and Ian F. Tannock, Princess Margaret Cancer Centre, University of Toronto; Sean B. Rourke, Tsegaye Bekele, and Haibo Zhang, St Michael's Hospital, University of Toronto, Toronto; and Gregory R. Pond, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Haryana M
authors.initials: HM
authors.lastname: Dhillon
authors.affiliation: Janette L. Vardy, Haryana M. Dhillon, Corrinne Renton, and Stephen Clarke, University of Sydney; Janette L. Vardy and Philip Beale, Concord Cancer Centre, Sydney, New South Wales, Australia; Janette L. Vardy, Anna Dodd, and Ian F. Tannock, Princess Margaret Cancer Centre, University of Toronto; Sean B. Rourke, Tsegaye Bekele, and Haibo Zhang, St Michael's Hospital, University of Toronto, Toronto; and Gregory R. Pond, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.affiliation: Janette L. Vardy, Haryana M. Dhillon, Corrinne Renton, and Stephen Clarke, University of Sydney; Janette L. Vardy and Philip Beale, Concord Cancer Centre, Sydney, New South Wales, Australia; Janette L. Vardy, Anna Dodd, and Ian F. Tannock, Princess Margaret Cancer Centre, University of Toronto; Sean B. Rourke, Tsegaye Bekele, and Haibo Zhang, St Michael's Hospital, University of Toronto, Toronto; and Gregory R. Pond, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sean B
authors.initials: SB
authors.lastname: Rourke
authors.affiliation: Janette L. Vardy, Haryana M. Dhillon, Corrinne Renton, and Stephen Clarke, University of Sydney; Janette L. Vardy and Philip Beale, Concord Cancer Centre, Sydney, New South Wales, Australia; Janette L. Vardy, Anna Dodd, and Ian F. Tannock, Princess Margaret Cancer Centre, University of Toronto; Sean B. Rourke, Tsegaye Bekele, and Haibo Zhang, St Michael's Hospital, University of Toronto, Toronto; and Gregory R. Pond, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Tsegaye
authors.initials: T
authors.lastname: Bekele
authors.affiliation: Janette L. Vardy, Haryana M. Dhillon, Corrinne Renton, and Stephen Clarke, University of Sydney; Janette L. Vardy and Philip Beale, Concord Cancer Centre, Sydney, New South Wales, Australia; Janette L. Vardy, Anna Dodd, and Ian F. Tannock, Princess Margaret Cancer Centre, University of Toronto; Sean B. Rourke, Tsegaye Bekele, and Haibo Zhang, St Michael's Hospital, University of Toronto, Toronto; and Gregory R. Pond, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Corrinne
authors.initials: C
authors.lastname: Renton
authors.affiliation: Janette L. Vardy, Haryana M. Dhillon, Corrinne Renton, and Stephen Clarke, University of Sydney; Janette L. Vardy and Philip Beale, Concord Cancer Centre, Sydney, New South Wales, Australia; Janette L. Vardy, Anna Dodd, and Ian F. Tannock, Princess Margaret Cancer Centre, University of Toronto; Sean B. Rourke, Tsegaye Bekele, and Haibo Zhang, St Michael's Hospital, University of Toronto, Toronto; and Gregory R. Pond, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Dodd
authors.affiliation: Janette L. Vardy, Haryana M. Dhillon, Corrinne Renton, and Stephen Clarke, University of Sydney; Janette L. Vardy and Philip Beale, Concord Cancer Centre, Sydney, New South Wales, Australia; Janette L. Vardy, Anna Dodd, and Ian F. Tannock, Princess Margaret Cancer Centre, University of Toronto; Sean B. Rourke, Tsegaye Bekele, and Haibo Zhang, St Michael's Hospital, University of Toronto, Toronto; and Gregory R. Pond, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Janette L. Vardy, Haryana M. Dhillon, Corrinne Renton, and Stephen Clarke, University of Sydney; Janette L. Vardy and Philip Beale, Concord Cancer Centre, Sydney, New South Wales, Australia; Janette L. Vardy, Anna Dodd, and Ian F. Tannock, Princess Margaret Cancer Centre, University of Toronto; Sean B. Rourke, Tsegaye Bekele, and Haibo Zhang, St Michael's Hospital, University of Toronto, Toronto; and Gregory R. Pond, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Beale
authors.affiliation: Janette L. Vardy, Haryana M. Dhillon, Corrinne Renton, and Stephen Clarke, University of Sydney; Janette L. Vardy and Philip Beale, Concord Cancer Centre, Sydney, New South Wales, Australia; Janette L. Vardy, Anna Dodd, and Ian F. Tannock, Princess Margaret Cancer Centre, University of Toronto; Sean B. Rourke, Tsegaye Bekele, and Haibo Zhang, St Michael's Hospital, University of Toronto, Toronto; and Gregory R. Pond, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Clarke
authors.affiliation: Janette L. Vardy, Haryana M. Dhillon, Corrinne Renton, and Stephen Clarke, University of Sydney; Janette L. Vardy and Philip Beale, Concord Cancer Centre, Sydney, New South Wales, Australia; Janette L. Vardy, Anna Dodd, and Ian F. Tannock, Princess Margaret Cancer Centre, University of Toronto; Sean B. Rourke, Tsegaye Bekele, and Haibo Zhang, St Michael's Hospital, University of Toronto, Toronto; and Gregory R. Pond, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Tannock
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016022:Case-Control Studies; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009483:Neuropsychological Tests; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D011795:Surveys and Questionnaires; D055815:Young Adult