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Introduction: Although a majority of the American public prefer to die at home, a large percentage of Parkinson's disease patients die in acute care hospitals. We examine trends in the clinical and demographic characteristics of Parkinson's disease patients who die in a hospital to identify populations potentially vulnerable to unwanted inpatient mortality. Methods: Patients with Parkinson's disease admitted to a hospital from 2002-2016 were identified from the National Inpatient Sample (n = 710,013) along with their associated clinical and demographic characteristics. The main outcome examined was mortality during inpatient admission. From these data, logistic regression models were estimated to obtain the odds ratios of inpatient mortality among clinical and demographic attributes, and their change over time. Results: Characteristics significantly associated with increased odds of inpatient mortality included increased age (OR = 1.70 for 55-65, 2.52 for 66-75, 3.99 for 76-85, 5.72 for 86+, all P < 0.001), length of stay ≤5 days (reference; 6 + days OR = 0.37, P < 0.001), white race or ethnicity (reference; Black OR = .84 P < .001, Hispanic OR = 0.91 P = 0.01), male (reference; female OR = 0.93 P < 0.001), hospitalization in Northeast (reference; Midwest OR = 0.78, South 0.84, West OR = 0.82; all P < 0.001), higher severity of illness (moderate OR = 1.50, major OR = 2.32, extreme OR = 5.57; all P < 0.001), and mortality risk (moderate OR = 2.88, major OR = 10.92, extreme OR = 52.30; all P < 0.001). Fitted probabilities overall declined over time. Conclusion: Differences exist among PD patient populations regarding likelihood of in-hospital mortality that are changing with time. Insight into which PD patients are most at risk for inpatient mortality may enable clinicians to better meet end-of-life care needs.
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UNLABELLED: Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia behind Alzheimer's disease (AD). It is estimated that 40% of AD patients also have some form of VCID. One promising therapeutic for AD is anti-Aß immunotherapy, which uses antibodies against Aß to clear it from the brain. While successful in clearing Aß and improving cognition in mice, anti-Aß immunotherapy failed to reach primary cognitive outcomes in several different clinical trials. We hypothesized that one potential reason the anti-Aß immunotherapy clinical trials were unsuccessful was due to this high percentage of VCID comorbidity in the AD population. We used our unique model of VCID-amyloid comorbidity to test this hypothesis. We placed 9-month-old wild-type and APP/PS1 mice on either a control diet or a diet that induces hyperhomocysteinemia (HHcy). After being placed on the diet for 3 months, the mice then received intraperotineal injections of either IgG2a control or 3D6 for another 3 months. While we found that treatment of our comorbidity model with 3D6 resulted in decreased total Aß levels, there was no cognitive benefit of the anti-Aß immunotherapy in our AD/VCID mice. Further, microhemorrhages were increased by 3D6 in the APP/PS1/control but further increased in an additive fashion when 3D6 was administered to the APP/PS1/HHcy mice. This suggests that the use of anti-Aß immunotherapy in patients with both AD and VCID would be ineffective on cognitive outcomes. SIGNIFICANCE STATEMENT: Despite significant mouse model data demonstrating both pathological and cognitive efficacy of anti-Aß immunotherapy for the treatment of Alzheimer's disease, clinical trial outcomes have been underwhelming, failing to meet any primary endpoints. We show here that vascular cognitive impairment and dementia (VCID) comorbidity eliminates cognitive efficacy of anti-Aß immunotherapy, despite amyloid clearance. Further, cerebrovascular adverse events of the anti-Aß immunotherapy are significantly exacerbated by the VCID comorbidity. These data suggest that VCID comorbidity with Alzheimer's disease may mute the response to anti-Aß immunotherapy.
