Cancer-related Cognitive Impairment
Conditions
Keywords
Cancer-related Cognitive Impairment, Cognitive Dysfunction, Cognition Disorders, Neurocognitive Disorder, Testosterone, Endocrinology, Testicular Cancer, Prostate Cancer
Brief summary
The primary aim of the study is - in a prospective controlled design - to examine whether treatment-induced decreases in testosterone acts as a mechanism of cancer-related cognitive impairment (CRCI) in testicular and prostate cancer patients. Secondary aims are 1) to explore whether decreases in testosterone interacts with increasing age to cause more severe CRCI in older patients, 2) to explore underlying neurophysiological (brain morphology) mechanisms of CRCI, and 3) to evaluate selected genetic variants as possible moderators of CRCI.
Detailed description
The study will include three groups with a total of 120 participants: A) Forty testicular cancer patients will be included and examined 1) shortly after orchiectomy and prior to any further treatment and 2) at 6 months' follow- up. B) Forty prostate cancer patients will be included and examined at two time-points: 1) prior to initiation of medical castration and radiotherapy and 2) at 6 months' follow- up. C) Forty age- and education-matched healthy controls will be included and assessed at a similar time-interval, i.e., at an initial examination and at a 6 month follow-up. Measures include a battery of neuropsychological/ cognitive tests, questionnaires, blood samples, and Magnetic Resonance Imaging (MRI). Primary hypothesis 1. Treatment-induced decreases in testosterone will be associated with decline in global cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients. Secondary hypotheses 2. Treatment-induced decreases in testosterone will be associated with decline in individual cognitive domains (i.e., processing speed, attention, verbal fluency, executive functioning, working memory, verbal learning and memory, visuospatial learning and memory, and visuospatial ability) from baseline to 6 months' follow- up in both testicular and prostate cancer patients. 3. Decline in cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients will correspond to changes in grey matter as measured by T1-weighted MRI. 4. Decline in cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients will correspond to changes in brain white matter as measured with diffusion-weighted MRI. 5. Treatment-induced decreases in testosterone will be more strongly associated with decline in cognitive functioning in prostate cancer patients compared with testicular cancer patients due to more advanced age in the former group. 6. Treatment-induced decreases in testosterone will be more strongly associated with decline in cognitive functioning in both testicular and prostate cancer patients carrying the the Apolipoprotein E (APOE) ε4 allele, the Val catechol-O-methyltranferase (COMT) allele, the Val/Val Brain- derived neurotrophic factor (BDNF) genotype, and a short polymorphic CAG repeat length of the Androgen Receptor (AR) gene. 7. Treatment-induced decreases in testosterone will be associated with increases in neurobehavioral symptoms (i.e., apathy, executive dysfunction, and disinhibition) from baseline to 6 months' follow- up in both testicular and prostate cancer patients. 8. Treatment-induced decreases in testosterone will be associated with decreases in health-related quality of life from baseline to 6 months' follow- up in both testicular and prostate cancer patients. 9. Treatment-induced decreases in testosterone will be associated with decreases in perceived cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients.
Interventions
None listed
Sponsors
Aarhus University Hospital
University of Aarhus
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Confirmed diagnosis of testicular cancer * Confirmed diagnosis of prostate cancer and prescription of medical castration and radiotherapy
Exclusion criteria
* Previous cancer disease * Previous central nervous system disease * Brain metastases * Severe psychiatric disease (e.g., schizophrenia, major depressive disorder) * Insufficient Danish proficiency for neuropsychological testing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global cognitive functioning | Baseline and 6 months' follow-up | Changes in global cognitive composite score as measured with neuropsychological tests specified under Secondary Outcome Measures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visuospatial ability | Baseline and 6 months' follow-up | Changes in visuospatial ability as measured with WAIS-IV Matrix Reasoning. |
| Processing speed | Baseline and 6 months' follow-up | Changes in processing speed as measured with Trail Making Test A. |
| Attention | Baseline and 6 months' follow-up | Changes in attention as measured with WAIS-IV Digit Span Forwards. |
| Executive functioning | Baseline and 6 months' follow-up | Changes in executive functioning as measured with Trail Making Test B. |
| Working memory | Baseline and 6 months' follow-up | Changes in working memory as measured with WAIS-IV Digit Span Sequencing. |
| Verbal fluency | Baseline and 6 months' follow-up | Changes in verbal fluency as measured with Controlled Oral Word Association Test. |
| Verbal learning and memory | Baseline and 6 months' follow-up | Changes in verbal learning and memory as measured with Hopkins Verbal Learning Test-Revised. |
| Visuospatial learning and memory | Baseline and 6 months' follow-up | Changes in visuospatial learning and memory as measured with WMS-III Visual Memory. |
| Testosterone levels | Baseline and 6 months' follow-up | Changes in testosterone levels as measured with liquid chromatography tandem mass spectrometry (LC-MS/MS). |
| Brain grey matter | Baseline and 6 months' follow-up | Changes in grey matter as measured with T1-weighted MRI. |
| Brain white matter | Baseline and 6 months' follow-up | Changes in brain white matter as measured with diffusion-weighted MRI. |
| Moderator: APOE genotype | Baseline | Genotype of the APOE gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphisms. |
| Moderator: COMT genotype | Baseline | Genotype of the COMT gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphism. |
| Moderator: BDNF genotype | Baseline | Genotype of the BDNF gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphism. |
| Moderator: CAG repeat length of the AR gene | Baseline | CAG repeat lenght of the AR gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphism. |
| Neurobehavioral symptoms (i.e., apathy, executive dysfunction, and disinhibition) | Baseline and 6 months' follow-up | Changes in neurobehavioral symptoms as measured with The Frontal Systems Behavior Scale (FrsBe). |
| Perceived cognitive functioning | Baseline and 6 months' follow-up | Changes in perceived cognitive functioning as measured with The Patient Assessment of Own Functioning Inventory (POAFI). |
| Health-related quality of life | Baseline and 6 months' follow-up | Changes in health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life questionnaire for cancer patients (EORTC QLQ-C30). |
| Health-related quality of life - Prostate Cancer | Baseline and 6 months' follow-up | Changes in disease specific health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life Prostate Cancer Module (EORTC QLQ-PR25). |
| Health-related quality of life - Testicular Cancer | Baseline and 6 months' follow-up | Changes in disease specific health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life Testicular Cancer Module (EORTC QLQ-TC25). |
Countries
Denmark
Outcome results
None listed