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Mild Cognitive Impairment in Men Following Androgen Deprivation Therapy for Prostate Cancer: a Longitudinal fMRI and qEEG Pilot Study.

50 Years
90 Years
Not Enrolling
Prostate Cancer

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Trial Information

Mild Cognitive Impairment in Men Following Androgen Deprivation Therapy for Prostate Cancer: a Longitudinal fMRI and qEEG Pilot Study.

Changes in cognitive function related to altered serum sex hormone levels are
well-recognised but poorly understood. Mild cognitive impairment (MCI) with aging is thought
in part to be related to reduction in serum androgen level and international studies are
on-going to prevent age-related MCI using androgen replacement therapy. Reduction in
cognitive function often leads to morbidity and reduction in quality of life. The commonest
therapeutically induced reduction in sex hormone level in men is in the treatment of
prostate cancer. As prostate cancer is androgen dependent for growth, androgen-deprivation
therapy (ADT) to suppress serum testosterone level to castration levels (< 1.7mM) is the key
therapeutic intervention for advanced disease. Up to 1 million men worldwide are estimated
to have been prescribed ADT for prostate cancer, mostly using luteinising hormone releasing
hormone agonists (LHRHa). ADT is now also used to treat some early prostate cancer and as
early asymptomatic prostate cancer is increasingly being diagnosed and treated following
screening with serum PSA measurement, estimates suggest that eventually up to 4% of all
Caucasians will be castrated.

MCI is a recognized side effect of ADT but little work has been done to quantify the effect,
understand the mechanism, predict which patients will be affected and determine ways of
reducing this side effect. Researching relationships of sex hormones and MCI should improve
understanding and interventions for slowing/preventing MCI in PCa survivors. Hormone
replacement therapy (HRT) in women slows the development of MCI. Alternatives for ADT
include parenteral oestrogens. The PATCH clinical trial comparing transdermal oestrogen with
LHRHa offers an opportunity to assess oestrogen as preventative for male MCI. Functional
magnetic resonance imaging (fMRI), quantitative electroencephalography (qEEG) and
neuropsychological tests will be used to test this hypothesis. Insight into the effect of
changes in serum sex hormones on MCI may provide a guide to improving MCI in aging and
improve the quality of life of prostate cancer survivors.

This study aims to (i) measure cognitive changes in prostate cancer patients receiving ADT
with either LHRHa or transdermal oestrogen and (ii) relate MCI to changes in serum hormone
levels. Simultaneous high-resolution fMRI of the brain and 64-channel qEEG will be used for
the first time in this patient group. MCI will be investigated by assessing changes in
parietal lobe activation to mental rotation tasks and changes in global resting-state fMRI
and qEEG activity and comparisons will be made with the cognitive assessment carried out by
neuropsychological tests.

Inclusion Criteria:

- Male patients between the ages 50 to 90 years beginning ADT with LHRHa or PATCH
participants randomised to either LHRHa or transdermal oestrogen for either newly
diagnosed advanced prostate cancer or previously treated with radical radiotherapy or
surgery and now having a rising prostate specific antigen will be included in the

Exclusion Criteria:

- Patients with a known history of dementia will be excluded as well as those patients
who have received any prior hormone therapy for localised prostate cancer.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label

Outcome Measure:

Objective evaluation of mild cognitive impairment on parietal fMRI signals

Outcome Description:

The primary outcome measure is the development of MCI following ADT with LHRHa, as evaluated by fMRI. The group change in the parietal blood oxygen level-dependent echoplanar imaging (BOLD EPI) fMRI signal associated with a three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Paul D Abel, ChM, FRCS

Investigator Role:

Study Chair

Investigator Affiliation:

Imperial College London and Imperial College Healthcare NHS Trust


United Kingdom: Research Ethics Committee

Study ID:




Start Date:

October 2012

Completion Date:

March 2014

Related Keywords:

  • Prostate Cancer
  • Mild cognitive impairment
  • Androgen deprivation therapy
  • Prostatic Neoplasms
  • Cognition Disorders