Oana C. Lindner, Martin G. McCabe, Andrew Mayes, Alison Wearden, Deborah Talmi School of Psychological Sciences University of Manchester

Transcription

1 Oana C. Lindner, Martin G. McCabe, Andrew Mayes, Alison Wearden, Deborah Talmi School of Psychological Sciences University of Manchester

2 Background Our preliminary results: Cognitive functioning in pre-treatment patients and survivors Psycho-social assessmentin pre-treatment patients and survivors Linksbetween cognition and psycho-social variables in both types of cancer patients Summary and future directions

3 Chemo-brain: effect of cancer chemotherapy on cognitive functioning Psycho-social factors: quality of life, anxiety, depression, fatigue, subjective cognitive complaints, illness perceptions. Consensus on impairments: Memory Attention Executive functions

4 International Cancer and Cognition Taskforce 30 groups in 11 countries

5 Incidence varies 0-80% (Vardy, et al.,2008, Ann.Oncology) Toxicity differences: chemotherapy, corticosteroids, hormones (Ahles & Saykin, 2007, Nature; Fardell et al., 2011, Nature; Lupien et al., 2002, Psychoneuroendocrinology) Trajectory of decline (de Ruiter et al., 2011, HBM) Risk factors or predictors (Ahles & Saykin, 2007 Nature)

6 Survivors of childhood acute lymphoblastic leukaemia N=567, mean age = 33, mean time since diagnosis = 26 years. Impairment across all cognitive functions: from 28.6% to 58.9% 2SDs less on IQ tests (in longitudinal studies) Younger age at diagnosis, increased survival time, and female gender associated with more impairments. Krull et al., JCO,2013

7 Imaging studies (special issue December, Brain, Behaviour & Imaging) grey matter, white matter, hippocampalvolume, medial prefrontal cortex activations. No links with depression, anxiety, quality of life, etc. although higher in patients. Meta-analysis of 44 studies shows: Selective attention, verbal immediate, delayed, recognition memory Results very sensitive to design type, practice effects, participant matching (especially on IQ). Lindner et al.(2014).a meta-analysis of cognitive impairment following adult cancer chemotherapy. Neuropsychology (in press).

8 Studies to date overly focused on: Breast cancer -> older age (m=52). Leukaemia -> young children (m=10), no selfassessment measures. Younger or older patients or survivors -> potential confound of naturally occurring brain development changes, thus neurocognitive changes. Other cancer groups less studied

9 Studies to date overly focused on: Breast cancer -> older age (m=52). Leukaemia -> young children (m=10), no selfassessment measures. Younger or older patients or survivors -> potential confound of naturally occurring brain development changes, thus neurocognitive changes. Other cancer groups less studied

10 Part 1 pre-treatment cognitive problems in young adults treated for non-cns malignancies. Part 2 neurocognitiveissues in young adult survivors of lymphoma, germ cell tumour, sarcoma, and breast cancer. Part 3 the impact of chemo-brain on psycho-social functioning.

11 Part 1 pre-treatment cognitive problems in young adults treated for non-cns malignancies. Part 2 neurocognitive issues in young adult survivors of lymphoma, germ cell tumour, sarcoma, and breast cancer. Part 3 the impact of chemo-brain on psycho-social functioning.

12 Part 1 pre-treatment cognitive problems in young adults treated for non-cns malignancies. Part 2 neurocognitive issues in young adult survivors of lymphoma, germ cell tumour, sarcoma, and breast cancer. Part 3 the impact of chemo-brain on psycho-social functioning.

13 Psycho-social variables Attention Memory

14 28 pre-treatment patients versus 28 healthy matched controls

15 75 survivors versus 72 healthy matched controls 6months to 5 years post-treatment (mean=2.5 years)

16 12 neuropsychological tests (57 scores): Wechsler Test of Adult Reading, D2 Concentration, Stroop, Test of Memory Malingering, BirtMemory and Information Processing Battery, Digit span, Verbal fluency, DKEFS Trail Making Task 6 psycho-social measures (19 scores): EORTC Info, Quality of Life, Hospital Anxiety and Depression Scale, Subjective Cognitive Complaints Questionnaire, Illness Perception Questionnaire, Fatigue Scale.

17 Testing group differences: Two MANCOVAs (for pre-treatment and survivors versus their respective controls): 2 groups*57 neuropsychological scores 3 groups*19 psycho-social variables Covariates: Age, Sex, Cancer Attention

18 Preliminary test of the model: Multivariate regressions Psycho-social factors (IVs) relation with Attention and Memory (DVs) Attention and Memory (IVs) relation with Psychosocial variables (DVs) Link between of Attention (IV) and Memory (DV)

19 Patients perform worse than controls (F=855.93, p<.001) on 19 scores: Age and sex -no influence. Cancer effect (F=214.96, p<.01) -Hodgkin s lymphoma more affected than other groups. Attention effect - impairments disappear

20 600 ** Attention 25 Executive functions ** ** ** 400 Performance ** New patients Controls Attention without errors Scores Concentration 0 Verbal fluency F Verbal fluency A Verbal fluency S Tests **p<.001

21 Visuo-spatial abilitesand memory * ** ** Working memory ** 20 Performance ** ** New patients Controls Visuo-spatial abilities Figure immediate Figure delayed Test 0 Digit span F Digit span B Digit span total Score **p<.001, *p<.05

22 Survivors perform worse than controls (F=3.32, p<.001) on 27 scores. Effect of Cancer (F=1.69, P<.001): Hodgkin s and non-hodgkin s lymphoma perform the worst Germ cell tumour cancer patients perform slightly better than other groups. Age and sex no influence. Effect of Attention: increases group differences.

23 600 Attention ** 70 ** Executive functions Performance ** * * Survivors Controls Attention without errors Score Concentration 0 Stroop Interference Verbal fluency F Test Verbal fluency S **p<.001, *p<.05

24 Story memory 80 ** 70 ** List learning and word recognition Performance ** ** ** * Survivors Controls Story immediate Story delayed Test Retention 0 Total words Word recognition Source recognition Test **p<.001, *p<.05

25 Visu0-spatial abilities and memory ** * * 80 Performance Survivors Controls 20 0 **p<.001, *p<.05 Visuo-spatial abilities Figure immediate Test Figure delayed Retention

26 Group effect (F=14.77, p<.001) when comparing all patients versus controls. No differences between the two cancer groups.

27 EORTC measures ** ** Performance ** Controls Survivors New Quality of Life Physical Functioning Symptoms Scales **p<.001, Survivors versus Pre-treatment not significant

28 ** Cognitive complaints, fatigue, distress Scores ** * * ** ** Controls Survivors New patients 0.0 Cognitive complaints Total fatigue Physical fatigue Mental fatigue Anxiety Depression Scales **p<.001, *p<.05, Survivors versus Pre-treatment not significant

29 Illness perceptions ** ** 20.0 Scores Survivors New patients 0.0 Scales **p<.001

30 Cognitive functions Psycho-social variables Attention Memory

31 Psycho-social variables Attention Memory Physical functioning Symptoms Fatigue Depression Complaints Concentration 5-9% variance in Psycho-social functioning 5-45% variance in Memory Verbal immediate and delayed Visual immediate and delayed Word recognition

32 Psycho-social variables Visual abilities, memory and information processing Illness perceptions QoL Anxiety Depression Symptoms Complaints 30-80% variance in Memory Figure Copy Figure Immediate Figure Retention List B List T SIP Speed SIP Adjusted Psycho-social variables explain the variance in Memory. Concentration explains the variance in both Psycho-social and Memory performance.

33 Psycho-social variables Physical functioning Symptoms 5-7% variance in attention Attention Concentration Stroop interference Visual scanning 7-26% variance in memory Memory Verbal memory: Immediate, delayed Verbal recognition Source memory

34 Psycho-social variables Physical functioning Symptoms Anxiety Depression 3-9% variance in memory Illness perceptions QoL Anxiety Depression Symptoms Complaints 2-14% variance in psycho-social functioningdue to memory Memory and Visuo-spatial abilities Verbal memory: Immediate, delayed Verbal recognition Source memory Visual memory: Delayed Visuo-spatial abilities Psychosocial variables relate to both attention and memory issues. Attention issues related to memory performance.

35 Pre-treatment patients are impaired on less cognitive tests before treatment. Including attentionas a covariate makes group differences disappear. Fatigue, distress, QoL, and illness perceptions influence attention. Attention performance relates to memory performance..

36 Survivors are impaired on more cognitive tests after treatment, especially lymphoma patients. Including attentionas a covariate increases group differences. Physical functioningand symptomsrelate to attention. Attention, depression, and anxietyrelate to memory performance, which relates to illness perceptions and cognitive complaints.

37 1. Mediation analyses and causal inferences 2. Increase sample size 3. Clinical trials: CBT, Cognitive training, physical exercise 4. Extend to imaging and translational studies

38 Participants who took part in our study My supervisors (Dr.Martin McCabe, Prof.Andrew Mayes, Prof. Alison Wearden, and Dr. Deborah Talmi) My advisor: Prof. Linda McGowan MRC NHS Trusts (Manchester, Liverpool, Macclesfield, Wigan, Swindon) Students who contributed to this work: Parker, M., Shaughnessy, K., Valiji, A., Williams, E. Thank you for your attention!