Androgen deprivation and cognition in prostate cancer

Abstract

Androgen deprivation (AD) is commonly used in neoadjuvant and adjuvant setting with prostate cancer (PC) radiotherapy. This prospective study assessed whether cognitive functioning is impaired during 12 months of AD therapy. Longitudinal testing of 25 patients treated with AD and curative radiotherapy was undertaken at baseline, and at 6 and 12 months. CogniSpeed r software was used for measuring attentional performances. Other cognitive performances were evaluated using verbal, visuomotor and memory tests. The Beck depression inventory was employed to evaluate depressive mood and EORTC QLQ-C30 for quality of life (QoL). During longitudinal testing of the AD group, no impairment in cognitive performances was found. Instead, improvement was observed in object recall (immediate, P ¼ 0.035; delayed, Po0.001), and in semantic memory (P ¼ 0.037). In QoL, impairment in physical function was observed. Androgen deprivation of 12 months appears to be associated with preserved cognitive functioning, although physical impairment occurs. These results have implications for counseling and psychosocial support of patients in the context of treatment options in PC.

Cognitive changes associated with ADT: a review of the literature

“…The search revealed a total of 11 studies examining ADT in relation to objective cognitive performance. [40][41][42] Our primary focus was effects on specific cognitive domains including verbal memory (e.g., memory for word lists), visual memory (e.g., memory for geometric designs), spatial memory (e.g., route memory), spatial abilities (e.g., mental rotations), attention, verbal fluency, processing speed, executive function (e.g., planning and mental flexibility) and working memory. Additionally, when available, we report findings based on a Reliable Change Index (RCI) calculation or a similar approach.…”

“…We review three studies with that simple design. [40][41][42] A better study design is one where the patient groups are tested at baseline and after treatment and compared to a control group tested at two sessions spaced at equal intervals. Such a design allows an estimation of change in performance related to ADT given what would be expected in the absence of ADT.…”

“…Salminen et al 40 conducted a prospective observational study of 23 men (mean age: 65 years) with non-metastatic prostate cancer receiving LHRH analog (leuprolid 11, 25 mg subcutaneously, four times a year for 3 months) and concurrent radiotherapy. Fifty-two controls were also tested at baseline only, so the effects of ADT on cognition could not be ascertained in relation to what would be expected in the absence of ADT and prostate cancer.…”

“…40,42 Observational studies comparing patients versus healthy controls over time Cherrier et al 47 conducted a prospective observational study involving a group of 19 men with non-metastatic prostate cancer in biochemical relapse treated with intermittent ADT (I-ADT) and a group of 15 healthy men (mean age of groups: 65 years). Patients were treated for 2 weeks with flutamide (250 mg, three times daily) or bicalutamide (50 mg daily) if intolerant of flutamide followed by the addition of leuprolide (7.5 mg intramuscular) for a total of nine monthly doses.…”

Psychological distress in men with prostate cancer receiving adjuvant androgen-deprivation therapy

“…Low testosterone levels may, in fact, alter serotonin neurotransmission [8], negatively affecting mood as demonstrated in animal models [9]. Also, testosterone deficiency may decrease cerebral perfusion in the brain regions involved in memory, reasoning, judgment, and emotions [10], leading to a deterioration in mental and overall wellbeing [11,12]. Studies in elderly subjects and non-cancer patients have reported a clear association between testosterone levels and depressive symptoms [13]: lower testosterone levels in older men have been associated with more depressive symptoms [14,15], which seem to disappear with testosterone hormone treatment [16,17].…”