Cognitive effects of long-term androgen deprivation therapy in older men with prostate cancer.

OBJECTIVE: Androgen deprivation therapy (ADT) is a common treatment for prostate cancer (PCa), with increasing numbers of men on ADT for longer. Limited evidence suggests ADT impacts cognition. This study addressed gaps in the literature by focusing on older men with PCa and assessing ADT usage longer than 1 year. METHODS: This study of 133 men ≥65 years of age with PCa included two groups: (1) men on ADT for 1-3 years (ADT-exposed), and (2) a comparison group of men with PCa not on ADT (ADT-unexposed). Group comparisons on individual neuropsychological test scores are reported, as well as effect sizes (Cohen's d). RESULTS: Half (n = 67) of the sample was ADT-exposed and half (n = 66) were unexposed. The average age was 72 years, most were White, and over 50% had at least secondary education. There were no statistically significant differences between groups by age, race, or education. Unadjusted analyses showed the ADT-exposed group, compared with the ADT-unexposed group, performed significantly lower in domains of verbal learning (d = 0.45-0.52, p = 0.01 to <0.01), verbal recall (d = 0.33-0.54, p = 0.06 to <0.01), and possible effects in visuospatial construction (d = 0.33, p = 0.08 to 0.06). When controlling for age and education, similar patterns emerged. The ADT exposed-group performed significantly lower in domains of verbal learning (d = 0.45-0.52, p = 0.06 to 0.03) and verbal recall (d = 0.33-0.54, p = 0.11 to 0.03), and possible effects in visuospatial construction d = 0.33, p = 0.18 to 0.13. CONCLUSIONS: This study suggests long-term ADT exposure impacts verbal learning, verbal recall, and possibly visuospatial abilities in older men (≥65) with PCa. The potential cognitive effects of ADT should be discussed with older patients considering long-term use of ADT.

Exercise Associated with Cognitive Function in Older Men with Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: To examine associations between exercise and cognitive function in older men undergoing hormone therapy for prostate cancer. METHOD: Men ≥ 65 years old with prostate cancer, currently undergoing androgen deprivation therapy for ≥ 6 months (n = 50), completed the Godin-Shephard Leisure-Time Physical Activity Questionnaire, and standard neuropsychological tests. Pearson's correlations and linear regressions were used to examine associations between exercise and cognitive performance. RESULTS: Exercise was significantly positively correlated with performance on tests of memory, attention, and executive function. Linear regressions showed that when controlling for age and education, exercise remained a significant predictor of attention and executive function performance (p < 0.05), and showed moderate, but statistically non-significant effects on memory performance (p < 0.10). CONCLUSION: Greater exercise is associated with better functioning in multiple cognitive domains in men with prostate cancer undergoing hormone therapy, providing proof-of-concept evidence that exercise may be a feasible intervention to limit cognitive dysfunction in prostate cancer patients.

99mTechnetium pyrophosphate scintigraphy with cadmium zinc telluride cameras is a highly sensitive and specific imaging modality to diagnose transthyretin cardiac amyloidosis.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR) is a rare, but underdiagnosed, cardiomyopathy. Traditionally diagnosed invasively, ATTR can be diagnosed with non-invasive 99mTechnetium pyrophosphate (99mTc-PYP) planar scintigraphy. Non-planar imaging has not been validated for ATTR diagnosis. Here, we develop and validate a Cadmium Zinc Telluride (CZT) protocol for diagnosing ATTR. METHODS: Forty-three subjects (24 ATTR, 19 non-ATTR) were imaged with Philips Dual-Head Anger (planar) and General Electric CZT cameras. Myocardial uptake was quantified by heart-to-contralateral (H/CL) ratios. CZT scans were quantified by two readers blinded to planar H/CL, with one repeating blinded quantification. Using the previously validated diagnostic threshold (H/CL ≥ 1.5), sensitivity and specificity of CZT scintigraphy was measured. McNemar's test and Pearson's correlation coefficient were calculated. RESULTS: Among subjects (76.7% male, age 77 ± 9), there was no significant difference in proportion of ATTR-positive identification between modalities. There was high correlation between CZT and planar H/CL ratios (r = 0.92, P < 0.0001), with low intra- [ICC = 0.89 (0.80-0.94)] and inter-observer [ICC = 0.80 (0.65-0.89)] variability. CZT scintigraphy had 100% sensitivity and specificity for diagnosing ATTR. CONCLUSION: 99mTc-PYP CZT imaging is as highly sensitive and specific diagnosing ATTR as planar imaging. These findings are clinically salient given the emergence of disease-modifying ATTR therapies, as it could expand diagnostic capability.

Diagnosing Transthyretin Cardiac Amyloidosis by Technetium Tc 99m Pyrophosphate: A Test in Evolution.

OBJECTIVES: This study aimed to characterize trends in technetium Tc 99m pyrophosphate (99mTc-PYP) scanning for amyloid transthyretin cardiac amyloidosis (ATTR-CA) diagnosis, to determine whether patients underwent appropriate assessment with monoclonal protein and genetic testing, to evaluate use of single-photon emission computed tomography (SPECT) in addition to planar imaging, and to identify predictive factors for ATTR-CA. BACKGROUND: 99mTc-PYP scintigraphy has been repurposed for noninvasive diagnosis of ATTR-CA. Increasing use of 99mTc-PYP can facilitate identification of ATTR-CA, but appropriate use is critical for accurate diagnosis in an era of high-cost targeted therapeutics. METHODS: Patients undergoing 99mTc-PYP scanning 1 h after injection at a quaternary care center from 2010 to 2019 were analyzed; clinical information was abstracted; and SPECT results were analyzed. RESULTS: Over the decade, endomyocardial biopsy rates remained stable with scanning rates peaking at 132 in 2019 (p < 0.001). Among 753 patients (516 men, mean age 77 years), 307 (41%) had a visual score of 0, 177 (23%) of 1, and 269 (36%) of 2 or 3. Of 751 patients with analyzable heart to contralateral chest ratios, 249 (33%) had a ratio ≥1.5. Monoclonal protein testing status was assessed in 550 patients, of these, 174 (32%) did not undergo both serum immunofixation and serum free light chain analysis tests, and 331 (60%) did not undergo all 3 tests-serum immunofixation, serum free light chain analysis, and urine protein electrophoresis. Of 196 patients with confirmed ATTR-CA, 143 (73%) had genetic testing for transthyretin mutations. In 103 patients undergoing cardiac biopsy, grades 2 and 3 99mTc-PYP had sensitivity of 94% and specificity of 89% for ATTR-CA with 100% specificity for grade 3 scans. With respect to SPECT as a reference standard, planar imaging had false positive results in 16 of 25 (64%) grade 2 scans. CONCLUSIONS: Use of noninvasive testing with 99mTc-PYP scanning for evaluation of ATTR-CA is increasing, and the inclusion of monoclonal protein testing and SPECT imaging is crucial to rule out amyloid light chain amyloidosis and distinguish myocardial retention from blood pooling.

The use of serial cardiac 18F-fluorodeoxyglucose- positron emission tomography imaging to diagnose, monitor, and tailor treatment of cardiac sarcoidosis patients with arrhythmias: a case series and review.

BACKGROUND: Clinically evident cardiac involvement has been documented in 5% of sarcoidosis patients, primarily manifesting as heart block, ventricular arrhythmias, and heart failure. Heart Rhythm Society consensus guidelines recommend advanced cardiac imaging with fluorodeoxyglucose-positron emission tomography (FDG-PET) scan for diagnosis of cardiac sarcoidosis, given endomyocardial biopsy's low sensitivity. CASE SUMMARY: We describe four patients with cardiac sarcoidosis diagnosed with FDG-PET scan performed using a standardized imaging protocol for cardiac sarcoidosis. Serial FDG-PET scans were performed to monitor disease progression and response to therapy. Patients 1 and 2 presented with heart block, Patient 3 with heart failure and ventricular tachycardia (VT), and Patient 4 with VT. Patient 1 showed an initial decrease in standard uptake value (SUV) on immunosuppression, followed by an increase in SUV, necessitating steroid therapy. Patient 2's SUV decreased on immunosuppression. Patient 3 required 3.5 years of immunosuppression for the SUV to decrease to inactive disease levels, with SUV increasing and decreasing at different times during treatment, and subsequently developed VT. For Patient 4, areas of inflammation on the initial scan matched low voltage areas on the patient's EP study, confirming the arrhythmia's pathophysiological basis. DISCUSSION: Cardiac sarcoidosis progression and response to therapy are heterogeneous. Serial FDG-PET scans are useful to diagnose disease, tailor therapy, and monitor the clinical course of disease, allowing treatment decisions to be based on the quantitative level of inflammation seen on FDG-PET.