Isabel Elaine Allen

Importance: Growing evidence suggests an association between sleep-disordered breathing (SDB) and cognitive decline in elderly persons. However, results from population-based studies have been conflicting, possibly owing to different methods to assess SDB or cognitive domains, making it difficult to draw conclusions on this association. Objective: To provide a quantitative synthesis of population-based studies on the relationship between SDB and risk of cognitive impairment. Data Sources: PubMed, EMBASE, and PsychINFO were systematically searched to identify peer-reviewed articles published in English before January 2017 that reported on the association between SDB and cognitive function. Study Selection: We included cross-sectional and prospective studies with at least 200 participants with a mean participant age of 40 years or older. Data Extraction and Synthesis: Data were extracted independently by 2 investigators. We extracted and pooled adjusted risk ratios from prospective studies and standard mean differences from cross-sectional studies, using random-effect models. This meta-analysis followed the PRISMA guidelines and also adhered to the MOOSE guidelines. Main Outcomes and Measures: Cognitive outcomes were based on standard tests or diagnosis of cognitive impairment. Sleep-disordered breathing was ascertained by apnea-hypopnea index or clinical diagnosis. Results: We included 14 studies, 6 of which were prospective, covering a total of 4 288 419 men and women. Pooled analysis of the 6 prospective studies indicated that those with SDB were 26% (risk ratio, 1.26; 95% CI, 1.05-1.50) more likely to develop cognitive impairment, with no evidence of publication bias but significant heterogeneity between studies. After removing 1 study that introduced significant heterogeneity, the pooled risk ratio was 1.35 (95% CI, 1.11-1.65). Pooled analysis of the 7 cross-sectional studies suggested that those with SDB had slightly worse executive function (standard mean difference, -0.05; 95% CI, -0.09 to 0.00), with no evidence of heterogeneity or publication bias. Sleep-disordered breathing was not associated with global cognition or memory. Conclusions and Relevance: Sleep-disordered breathing is associated with an increased risk of cognitive impairment and a small worsening in executive function. Further studies are required to determine the mechanisms linking these common conditions and whether treatment of SDB might reduce risk of cognitive impairment.

Importance: Few health systems have adopted effective dementia care management programs. The Care Ecosystem is a model for delivering care from centralized hubs across broad geographic areas to caregivers and persons with dementia (PWDs) independently of their health system affiliations. Objective: To determine whether the Care Ecosystem is effective in improving outcomes important to PWDs, their caregivers, and payers beyond those achieved with usual care. Design, Setting, and Participants: A single-blind, randomized clinical trial with a pragmatic design was conducted among PWDs and their caregivers. Each PWD-caregiver dyad was enrolled for 12 months between March 20, 2015, and February 28, 2017. Data were collected until March 5, 2018. Study interventions and assessments were administered over the telephone and internet by clinical and research teams in San Francisco, California, and Omaha, Nebraska. Of 2585 referred or volunteer PWD-caregiver dyads in California, Iowa, or Nebraska, 780 met eligibility criteria and were enrolled. A total of 512 PWD-caregiver dyads were randomized to receive care through the Care Ecosystem and 268 dyads to receive usual care. All eligible PWDs had a dementia diagnosis; were enrolled or eligible for enrollment in Medicare or Medicaid; and spoke English, Spanish, or Cantonese. Analyses were intention-to-treat. Intervention: Telephone-based collaborative dementia care was delivered by a trained care team navigator, who provided education, support and care coordination with a team of dementia specialists (advanced practice nurse, social worker, and pharmacist). Main Outcomes and Measures: Primary outcome measure: Quality of Life in Alzheimer's Disease based on caregiver's rating of 13 aspects of PWD's well-being (including physical health, energy level, mood, living situation, memory, relationships, and finances) on a 4-point scale (poor to excellent). Secondary outcomes: frequencies of PWDs' use of emergency department, hospitalization, and ambulance services; caregiver depression (score on 9-Item Patient Health Questionnaire; higher scores indicate more severe depression); and caregiver burden (score on 12-Item Zarit Burden Interview; higher scores indicate more severe caregiver burden). Results: The 780 PWDs (56.3% female; mean [SD] age, 78.1 [9.9] years) and 780 caregivers (70.9% female; mean [SD] age, 64.7 [12.0] years) lived in California (n = 452), Nebraska (n = 284), or Iowa (n = 44). Of 780 dyads, 655 were still active at 12 months, and 571 completed the 12-month survey. Compared with usual care, the Care Ecosystem improved PWD quality of life (B, 0.53; 95% CI, 0.25-1.30; P = .04), reduced emergency department visits (B, -0.14; 95% CI, -0.29 to -0.01; P = .04), and decreased caregiver depression (B, -1.14; 95% CI, -2.15 to -0.13; P = .03) and caregiver burden (B, -1.90; 95% CI, -3.89 to -0.08; P = .046). Conclusions and Relevance: Effective care management for dementia can be delivered from centralized hubs to supplement usual care and mitigate the growing societal and economic burdens of dementia. Trial Registration: ClinicalTrials.gov identifier: NCT02213458.

Ga-PSMA-11 PET is used to stage patients with prostate cancer. We performed an updated metaanalysis that separates imaging at the time of diagnosis and at the time of biochemical recurrence and focuses on pathology correlation in both populations. Methods: We searched the MEDLINE and EMBASE databases using the PRISMA statement. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool 2. In total, 1,811 studies were screened, 58 were analyzed, 41 were included for qualitative synthesis, and 29 were included for quantitative analysis. A random-effect model and a hierarchical summary receiver-operating-characteristic model were used to summarize the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy for pelvic lymph nodes in initial staging compared with pathology at prostatectomy and the PPV for lesions with pathologic correlation in those with biochemical recurrence. We also summarized the detection rate of 68 Ga-PSMA-11 in those with biochemical recurrence stratified by prostate-specific antigen (PSA) at the time of imaging. Results: The metaanalysis of 68 Ga-PSMA-11 at initial staging demonstrated a sensitivity and specificity of 0.74 (95% confidence interval [95% CI], 0.51-0.89) and 0.96 (95% CI, 0.85-0.99), respectively, using nodal pathology at prostatectomy as a gold standard. At biochemical recurrence, the PPV was 0.99 (95% CI, 0.96-1.00). The detection rate was 0.63 (95% CI, 0.55-0.70), with a PSA of less than 2.0 and 0.94 (95% CI, 0.91-0.96) with a PSA of more than 2.0. Conclusion: 68 Ga-PSMA-11 performed well for the localization of metastatic prostate cancer at initial staging and at the time of biochemical recurrence.