Cognitive changes associated with ADT: a review of the literature.
ABSTRACT: The use of androgen deprivation therapy (ADT) has increased since the early 1990s after early detection efforts and greater use of the prostate-specific antigen (PSA) test. Although ADT is associated with favorable clinical outcomes, ADT has been associated with an increased risk for cardiovascular disease, increased serum cholesterol, triglycerides, insulin resistance, body mass index and fat body mass. Here we review findings from 11 clinical studies examining the effects of ADT on cognition as measured by standardized tests in cognitive domains such as verbal and spatial memory. Most of these studies have important limitations, including small sample sizes, suboptimal control groups and baseline group differences in confounding factors. Despite these limitations, the best designed studies, those comparing patients on ADT to healthy controls, generally suggest that spatial memory might be especially sensitive to the effects of ADT. Critically, to date there is only one study involving random assignment of ADT versus close clinical observation. That study revealed a decrease in verbal memory with ADT, but was limited in sample size and did not include a measure of spatial memory. A recent observational study revealed no substantial evidence of cognitive impairment with ADT, even in the domain of verbal memory. Like the randomized study, however, this large observational study lacked a measure of spatial memory. Overall, the studies with the best controls suggest a potential negative impact of ADT on spatial memory, and perhaps verbal memory, and a need for continued investigation of the impact of ADT on cognition, particularly in these two cognitive domains.
Project description:Many prostate cancer (PCa) patients are on androgen deprivation therapy (ADT) as part of their cancer treatments but ADT may lead to cognitive impairments. ADT depletes men of both androgen and estrogen. Whether estradiol supplementation can improve cognitive impairments in patients on ADT is understudied.To summarize data on the effects of estradiol treatment on cognitive function of androgen-deprived genetic male populations (PCa patients and male-to-female transsexuals) and castrated male animals.Publications were identified by a literature search on PubMed and Google Scholar.While some studies showed that estradiol improves cognitive function (most notably, spatial ability) for castrated rats, what remains uninvestigated are: 1) whether estradiol can improve cognition after long-term androgen deprivation, 2) how estradiol affects memory retention, and 3) how early vs. delayed estradiol treatment after castration influences cognition. For androgendeprived genetic males, estradiol treatment may improve some cognitive functions (e.g., verbal and visual memory), but the findings are not consistent due to large variability in the study design between studies.Future studies are required to determine the best estradiol treatment protocol to maximize cognitive benefits for androgen-deprived genetic males. Tests that assess comparable cognitive domains in human and rodents are needed. What particularly under-investigated is how the effects of estradiol on cognitive ability intersect with other parameters; sleep, depression and physical fatigue. Such studies have clinical implications to improve the quality of life for both PCa patients on ADT as well as for male-to-female transsexuals.
Project description:Social relationships, which are contingent on access to social networks, promote engagement in social activities and provide access to social support. These social factors have been shown to positively impact health outcomes. In the current systematic review, we offer a comprehensive overview of the impact of social activities, social networks and social support on the cognitive functioning of healthy older adults (50+) and examine the differential effects of aspects of social relationships on various cognitive domains.We followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, and collated data from randomised controlled trials (RCTs), genetic and observational studies. Independent variables of interest included subjective measures of social activities, social networks, and social support, and composite measures of social relationships (CMSR). The primary outcome of interest was cognitive function divided into domains of episodic memory, semantic memory, overall memory ability, working memory, verbal fluency, reasoning, attention, processing speed, visuospatial abilities, overall executive functioning and global cognition.Thirty-nine studies were included in the review; three RCTs, 34 observational studies, and two genetic studies. Evidence suggests a relationship between (1) social activity and global cognition and overall executive functioning, working memory, visuospatial abilities and processing speed but not episodic memory, verbal fluency, reasoning or attention; (2) social networks and global cognition but not episodic memory, attention or processing speed; (3) social support and global cognition and episodic memory but not attention or processing speed; and (4) CMSR and episodic memory and verbal fluency but not global cognition.The results support prior conclusions that there is an association between social relationships and cognitive function but the exact nature of this association remains unclear. Implications of the findings are discussed and suggestions for future research provided.PROSPERO 2012: CRD42012003248 .
Project description:Prior research examining the impact of androgen deprivation therapy (ADT) for prostate cancer on cognitive performance has found inconsistent relationships. The purpose of this study was to systematically review the existing literature and determine the effect of ADT on performance across seven cognitive domains using meta-analysis.A search of PubMed Medline, PsycINFO, Cochrane Library, and Web of Knowledge/Science databases yielded 157 unique abstracts reviewed by independent pairs of raters. Fourteen studies with a total of 417 patients treated with ADT were included in the meta-analysis. Objective neuropsychological tests were categorized into seven cognitive domains: attention/working memory, executive functioning, language, verbal memory, visual memory, visuomotor ability, and visuospatial ability.Separate effect sizes were calculated for each cognitive domain using pairwise comparisons of patients who received ADT with (1) prostate cancer patient controls, (2) noncancer controls, or (3) ADT patients' own pre-ADT baselines. Patients treated with ADT performed worse than controls or their own baseline on visuomotor tasks (g =?-0.67, p =?.008; n = 193). The magnitude of the deficits was larger in studies with a shorter time to follow-up (p =?.04). No significant effect sizes were observed for the other six cognitive domains (p =?.08-.98).Prostate cancer patients who received ADT performed significantly worse on visuomotor tasks compared to noncancer control groups. These findings are consistent with the known effects of testosterone on cognitive functioning in healthy men. Knowledge of the cognitive effects of ADT may help patients and providers better understand the impact of ADT on quality of life.
Project description:Objective: To evaluate associations between depression and individual cognitive domains and how changes in depressive symptoms relate to cognition three years later in the context of Mexico, a developing country experiencing rapid aging.Method: Data comes from the 2012 and 2015 waves of the Mexican Health and Aging Study (n?=?12,898, age 50+). Depression is ascertained using a modified Center for Epidemiologic Studies - Depression Scale. Cognition is assessed using verbal learning, verbal memory, visual scanning, verbal fluency, visuospatial ability, visual memory, and orientation tasks. Depressive symptoms and cognitive functioning were both measured in 2012 and 2015. Scores across cognitive domains are modeled using ordinary least squares regression, adjusting for demographic, health, and economic covariates.Results: When depression and cognition were measured concurrently in 2015, depression exhibited associations with all cognitive domains. When considering a respondent's history of depression, individuals who had elevated depressive symptoms in 2012 and recovered by 2015 continued to exhibit poorer cognitive function in 2015 in verbal learning, verbal memory, visual scanning, and verbal fluency tasks compared to individuals who were neither depressed in 2012 nor 2015.Conclusions: Depression was associated with cognition across cognitive domains among older Mexican adults. Despite improvements in depressive symptomatology, formerly depressed respondents continued to perform worse than their counterparts without a history of depression on several cognitive tasks. In addition to current mental health status, researchers should consider an individual's history of depression when assessing the cognitive functioning of older adults.
Project description:Despite a lack of consensus regarding effectiveness, androgen deprivation therapy (ADT) is a common treatment for non-metastatic, low-risk prostate cancer. To examine a particular clinical concern regarding the possible impact of ADT on cognition, the current study combined neuropsychological testing with functional magnetic resonance imaging (fMRI) to assess both brain activation during cognitive performance as well as the integrity of brain connectivity.In a prospective observational cohort analysis of men with non-metastatic prostate cancer at a Veterans Affairs medical center, patients receiving ADT were compared with patients not receiving ADT at baseline and at 6?months. Assessments included fMRI, the N-back task (for working memory), the stop-signal task (for cognitive control), and a quality of life questionnaire.Among 36 patients enrolled (18 in each group), 30 completed study evaluations (15 in each group); 5 withdrew participation and 1 died. Results for the N-back task, stop-signal task, and quality of life were similar at 6?months vs. baseline in each group. In contrast, statistically significant associations were found between ADT use (vs. non use) and decreased medial prefrontal cortical activation during cognitive control, as well as decreased connectivity between the medial prefrontal cortex and other regions involved with cognitive control.Although ADT for 6?months did not affect selected tests of cognitive function, brain activations during cognitive control and functional brain connectivity were impaired on fMRI. The long-term clinical implications of these changes are not known and warrant future study.
Project description:Electric Extradural Motor Cortex Stimulation (EMCS) is a neurosurgical procedure suggested for treatment of patients with advanced Parkinson's disease (PD). We report two PD patients treated by EMCS, who experienced worsening of motor symptoms and cognition 5 years after surgery, when EMCS batteries became discharged. One month after EMCS restoration, they experienced a subjective improvement of motor symptoms and cognition. Neuropsychological assessments were carried out before replacement of batteries (off-EMCS condition) and 6 months afterward (on-EMCS condition). As compared to off-EMCS condition, in on-EMCS condition both patients showed an improvement on tasks of verbal episodic memory and backward spatial short-term/working memory task, and a decline on tasks of selective visual attention and forward spatial short-term memory. These findings suggest that in PD patients EMCS may induce slight beneficial effects on motor symptoms and cognitive processes involved in verbal episodic memory and in active manipulation of information stored in working memory.
Project description:A study was undertaken to relate dietary fat types to cognitive change in healthy community-based elders.Among 6,183 older participants in the Women's Health Study, we related intake of major fatty acids (saturated [SFA], monounsaturated [MUFA], total polyunsaturated [PUFA], trans-unsaturated) to late-life cognitive trajectory. Serial cognitive testing, conducted over 4 years, began 5 years after dietary assessment. Primary outcomes were global cognition (averaging tests of general cognition, verbal memory, and semantic fluency) and verbal memory (averaging tests of recall). We used analyses of response profiles and logistic regression to estimate multivariate-adjusted differences in cognitive trajectory and risk of worst cognitive change (worst 10%) by fat intake.Higher SFA intake was associated with worse global cognitive (p for linear trend = 0.008) and verbal memory (p for linear trend = 0.01) trajectories. There was a higher risk of worst cognitive change, comparing highest versus lowest SFA quintiles; the multivariate-adjusted odds ratio (OR) with 95% confidence interval (CI) was 1.64 (1.04-2.58) for global cognition and 1.65 (1.04-2.61) for verbal memory. By contrast, higher MUFA intake was related to better global cognitive (p for linear trend < 0.001) and verbal memory (p for linear trend = 0.009) trajectories, and lower OR (95% CI) of worst cognitive change in global cognition (0.52 [0.31-0.88]) and verbal memory (0.56 [0.34-0.94]). Total fat, PUFA, and trans-fat intakes were not associated with cognitive trajectory.Higher SFA intake was associated with worse global cognitive and verbal memory trajectories, whereas higher MUFA intake was related to better trajectories. Thus, different consumption levels of the major specific fat types, rather than total fat intake itself, appeared to influence cognitive aging.
Project description:The effects of testosterone (T) and estradiol (E(2)) on cognition in men are confounded in extant studies. This randomized, placebo-controlled trial was undertaken to investigate the possible effects of E(2) on cognition in older men. Twenty-five men with prostate cancer (mean age: 71.0+/-8.8 years) who required combined androgen blockade treatment were enrolled. Performance on cognitive tests was evaluated at pre-treatment baseline and following 12 weeks of treatment with a gonadotropin-releasing hormone analog and the nonsteroidal antiandrogen bicalutamide to determine whether specific cognitive functions would decline when the production of both T and E(2) were suppressed. In the second phase of the study, either micronized E(2) 1mg/day or an oral daily placebo was randomly added to the combined androgen blockade for an additional 12 weeks to determine whether E(2) would enhance performance in specific cognitive domains (verbal memory, spatial ability, visuomotor abilities and working memory). Compared to pretreatment, no differences in scores occurred on any cognitive test following 12 weeks of combined androgen blockade. In the add-back phase of the study (Visit 3), the placebo-treated men, but not the E(2)-treated men, exhibited a trend towards improvement in their scores on both the immediate (p=.075) and delayed recall (p=.095) portions of a verbal memory task compared to baseline. Moreover, at Visit 3, placebo-treated men performed significantly better than the E(2)-treated men on both the immediate (p=.020) and delayed recall (p=.016) portions of the verbal memory task. Thus, combined androgen blockade plus add-back E(2) failed to improve short- or long-term verbal memory performance in this sample of older men being treated for prostate cancer.
Project description:Little is known about the cognitive factors associated with adherence to antiestrogen therapy. Our objective was to investigate the association between domain-specific cognitive function and adherence among women in a clinical prevention trial of oral antiestrogen therapies. We performed a secondary analysis of Co-STAR, an ancillary study of the STAR breast cancer prevention trial in which postmenopausal women at increased breast cancer risk were randomized to tamoxifen or raloxifene. Co-STAR enrolled nondemented participants ?65 years old to compare treatment effects on cognition. The cognitive battery assessed global cognitive function (Modified Mini-Mental State Exam), and specific cognitive domains of verbal knowledge, verbal fluency, figural memory, verbal memory, attention and working memory, spatial ability, and fine motor speed. Adherence was defined by a ratio of actual time taking therapy per protocol ?80% of expected time. Logistic regression was used to evaluate the association between cognitive test scores and adherence to therapy. The mean age of the 1,331 Co-STAR participants was 67.2 ± 4.3 years. Mean 3MS score was 95.1 (4.7) and 14% were nonadherent. In adjusted analyses, the odds of nonadherence were lower for those with better scores on verbal memory [OR (95% confidence interval): 0.75 (0.62-0.92)]. Larger relative deficits in verbal memory compared with verbal fluency were also associated with nonadherence [1.28 (1.08-1.51)]. Among nondemented older women, subtle differences in memory performance were associated with medication adherence. Differential performance across cognitive domains may help identify persons at greater risk for poor adherence.
Project description:Studies of Alzheimer's disease risk-weighted polygenic risk scores (PRSs) for cognitive performance have reported inconsistent associations. This inconsistency is particularly evident when PRSs are assessed independent of APOE genotype. As such, the development and assessment of phenotype-specific weightings to derive PRSs for cognitive decline in preclinical AD is warranted. To this end a episodic memory-weighted PRS (emPRS) was derived and assessed against decline in cognitive performance in 226 healthy cognitively normal older adults with high brain Aβ-amyloid burden participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. The effect size for decline in a verbal episodic memory was determined individually for 27 genetic variants in a reference sample (n = 151). These were then summed to generate a emPRS either including APOE (emPRSc̅APOE) or excluding APOE (emPRSs̅APOE ). Resultant emPRS were then evaluated, in a test sample (n = 75), against decline in global cognition, verbal episodic memory and a pre-Alzheimer's cognitive composite (AIBL-PACC) over 7.5 years. The mean (SD) age of the 226 participants was 72.2 (6.6) years and 116 (51.3%) were female. Reference and test samples did not differ significantly demographically. Whilst no association of emPRSs were observed with baseline cognition, the emPRSc̅ APOE was associated with longitudinal global cognition (-0.237, P = 0.0002), verbal episodic memory (-0.259, P = 0.00003) and the AIBL-PACC (-0.381, P = 0.02). The emPRSs̅ APOE was also associated with global cognition (-0.169, P = 0.021) and verbal episodic memory (-0.208, P = 0.004). Stratification by APOE ε4 revealed that the association between the emPRS and verbal episodic memory was limited to carriage of no ε4 or one ε4 allele. This was also observed for global cognition. The emPRS and rates of decline in AIBL-PACC were associated in those carrying one ε4 allele. Overall, the described novel emPRS has utility for the prediction of decline in cognition in preclinical AD. This study provides evidence to support the further use and evaluation of phenotype weightings in PRS development.