No abstract

We confirmed the value of Ga-PSMA PET/CT in restaging PCa patients with BCR, highlighting its superior performance and safety compared with choline PET/CT. Higher PSApet was associated with a higher relapse detection rate.

Background: Family history of Alzheimer’s disease (AD) is associated with increased dementia-risk. Objective: The Israel Registry for Alzheimer’s Prevention (IRAP) is a prospective longitudinal study of asymptomatic middle-aged offspring of AD patients (family history positive; FH+) and controls (whose parents have aged without dementia; FH–) aimed to unravel the contribution of midlife factors to future cognitive decline and dementia. Here we present the study design, methods, and baseline characteristics. Methods: Participants are members of the Maccabi Health Services, 40–65 years of age, with exquisitely detailed laboratory, medical diagnoses and medication data available in the Maccabi electronic medical records since 1998. Data collected through IRAP include genetic, sociodemographic, cognitive, brain imaging, lifestyle, and health-related characteristics at baseline and every three years thereafter. Results: Currently IRAP has 483 participants [mean age 54.95 (SD = 6.68) and 64.8% (n = 313) women], 379 (78.5%) FH+, and 104 (21.5%) FH–. Compared to FH–, FH+ participants were younger (p = 0.011), more often males (p = 0.003) and with a higher prevalence of the APOE E4 allele (32.8% FH+, 22% FH–; p = 0.040). Adjusting for age, sex, and education, FH+ performed worse than FH–in global cognition (p = 0.027) and episodic memory (p = 0.022). Conclusion: Lower cognitive scores and higher rates of the APOE E4 allele among the FH+ group suggest that FH ascertainment is good. The combination of long-term historical health-related data available through Maccabi with the multifactorial information collected through IRAP will potentially enable development of dementia-prevention strategies already in midlife, a critical period in terms of risk factor exposure and initiation of AD-neuropathology.

No abstract

No abstract

Background Prostate cancer is a common malignancy of the elderly, and with the aging of the population, the need is growing for therapies suitable for this age group. Lutetium‐177–prostate‐specific membrane antigen (Lu‐PSMA), a radiolabeled small molecule, binds with high affinity to prostate‐specific membrane antigen, enabling beta particle therapy targeted to metastatic castration‐resistant prostate cancer (mCRPC). In a recent single‐arm phase II trial and a subsequent expansion cohort, a prostate‐specific antigen (PSA) decline of ≥50% was observed in approximately 60% of patients receiving Lu‐PSMA. Taking into account the specific challenges and potential toxicities of Lu‐PSMA administration in elderly men, we sought to retrospectively analyze the safety and activity of Lu‐PSMA in men aged older than 75 years with mCRPC. Patients and Methods The electronic medical records of 24 patients aged older than 75 years treated with Lu‐PSMA “off‐trial” were reviewed, and clinical data were extracted. Clinical endpoints were toxicity and activity, defined as a PSA decline ≥50%. Descriptive statistics were performed using Excel. Results The median age at treatment start was 81.7 years (range 75.1–91.9). The median number of previous treatment lines was four. The number of treatment cycles ranged from one to four; the mean administered radioactivity was 6 GBq per cycle. Treatment was generally tolerable; side effects included fatigue (n = 8, 33%), anemia (n = 7, 29%), thrombocytopenia (n = 5, 21%), and anorexia/nausea (n = 3, 13%). Clinical benefit was observed in 12 of 22 patients (54%); PSA decline above 50% was observed in 11 patients (48%) and was associated with significantly longer overall survival. Conclusion Our results indicate that Lu‐PSMA is safe and active in elderly patients with mCRPC. Implications for Practice Lutetium‐177–prostate‐specific membrane antigen (Lu‐PSMA), a radiolabeled small molecule, binds with high affinity to prostate‐specific membrane antigen, enabling beta particle therapy targeted to metastatic castration‐resistant prostate cancer (mCRPC). The recently published single‐arm phase II trial with Lu‐PSMA, describing its safety and activity, did not include patients aged older than 75 years. In this study, Lu‐PSMA activity was retrospectively analyzed in patients aged older than 75 years and results indicate that treatment was tolerable and similarly active in this age group, with no new emerging safety signals. Despite the small cohort size, this analysis suggests that Lu‐PSMA can serve as an advanced palliative treatment line in mCRPC in elderly patients.

No abstract

Introduction Type 2 diabetes (T2D) is a risk factor for dementia. Ischemia due to vascular pathology is hypothesized to be an underlying mechanism for this association. Hyperbaric oxygen therapy (HBOT) is a treatment in which oxygen‐enriched air (up to 100%) is administered to patients in a chamber at a pressure above one atmosphere absolute. HBOT is approved for the treatment of T2D ischemic non‐healing wounds. Evidence from animal studies and small clinical trials suggests that HBOT improves hypoxic/ischemic brain injuries, consequently inducing brain angiogensis, leading to cognitive improvement. Methods We present the design of the first double‐blind, placebo‐controlled, clinical trial on brain and cognitive outcomes in elderly (n = 154) with T2D and mild cognitive impairment to compare the effects of HBOT versus sham (normal air with 1.1 ATA pressure in the first and last 5 minutes of the session). Eligible candidates are randomized with equal probability to HBOT and sham. Outcomes are assessed before and after treatment, and at 6‐ and 12‐month follow‐up. The primary cognitive outcome is global cognitive change, indexed by a composite sum of z‐scores of four executive functions and four episodic memory tests. The primary neurobiological outcome is cerebral blood flow (CBF; via arterial spin labeling magnetic resonance imaging [ASL‐MRI]) and cerebral glucose utilization via fluorodeoxyglucose positron emission tomography (FDG‐PET). Secondary outcome measures are specific cognitive domains (executive function and episodic memory) and functional measures (Clinical Dementia Rating sum of boxes, activities of daily living). Efficacy analyses will be performed for the intent‐to‐treat sample. Discussion Recent studies suggest that HBOT induces neuroplasticity and improves cognition in post‐stroke and traumatic brain injury patients. However, its effect on cognition, cerebral blood flow, and brain glucose utilization in T2D patients at high dementia risk is yet to be determined. If effective, this study may provide strong evidence for the brain and cognitive benefits of HBOT in this population.