Impact of Non-pharmacological Chronic Hypertension on a Transgenic Rat Model of Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy (CAA), a common comorbidity of Alzheimer's disease (AD), is a cerebral small vessel disease (CSVD) characterized by deposition of fibrillar amyloid ß (Aß) in blood vessels of the brain and promotes neuroinflammation and vascular cognitive impairment and dementia (VCID). Hypertension, a prominent non-amyloidal CSVD, has been found to increase risk of dementia, but clinical data regarding its effects in CAA patients is controversial. To understand the effects of hypertension on CAA, we bred rTg-DI transgenic rats, a model of CAA, with spontaneously hypertensive, stroke prone (SHR-SP) rats producing bigenic rTg-DI/SHR-SP and non-transgenic SHR-SP littermates. At 7 months (M) of age, cohorts of both rTg-DI/SHR-SP and SHR-SP littermates exhibit elevated systolic blood pressures. However, transgene human amyloid ß-protein (Aß) precursor and Aß peptide levels, as well as behavioral testing showed no changes between bigenic rTg-DI/SHR-SP and rTg-DI rats. Subsequent cohorts of rats were aged further to 10 M where bigenic rTg-DI/SHR-SP and SHR-SP littermates exhibit elevated systolic and diastolic blood pressures. Vascular amyloid load in hippocampus and thalamus was significantly decreased, whereas pial surface vessel amyloid increased, in bigenic rTg-DI/SHR-SP rats compared to rTg-DI rats suggesting a redistribution of vascular amyloid in bigenic animals. There was activation of both astrocytes and microglia in rTg-DI rats and bigenic rTg-DI/SHR-SP rats not observed in SHR-SP rats indicating that glial activation was likely in response to the presence of vascular amyloid. Thalamic microbleeds were present in both rTg-DI rats and bigenic rTg-DI/SHR-SP rats. Although the number of thalamic small vessel occlusions were not different between rTg-DI and bigenic rTg-DI/SHR-SP rats, a significant difference in occlusion size and distribution in the thalamus was found. Proteomic analysis of cortical tissue indicated that bigenic rTg-DI/SHR-SP rats largely adopt features of the rTg-DI rats with enhancement of certain changes. Our findings indicate that at 10 M of age non-pharmacological hypertension in rTg-DI rats causes a redistribution of vascular amyloid and significantly alters the size and distribution of thalamic occluded vessels. In addition, our findings indicate that bigenic rTg-DI/SHR-SP rats provide a non-pharmacological model to further study hypertension and CAA as co-morbidities for CSVD and VCID.

Sex Differences in Metabolic Indices and Chronic Neuroinflammation in Response to Prolonged High-Fat Diet in ApoE4 Knock-In Mice.

Late-onset Alzheimer's disease (LOAD) likely results from combinations of risk factors that include both genetic predisposition and modifiable lifestyle factors. The E4 allele of apolipoprotein E (ApoE) is the most significant genetic risk factor for LOAD. A Western-pattern diet (WD) has been shown to strongly increase the risk of cardiovascular disease and diabetes, conditions which have been strongly linked to an increased risk for developing AD. Little is known about how the WD may contribute to, or enhance, the increased risk presented by possession of the ApoE4 allele. To model this interaction over the course of a lifetime, we exposed male and female homozygote ApoE4 knock-in mice and wild-type controls to nine months of a high-fat WD or standard chow diet. At eleven months of age, the mice were tested for glucose tolerance and then for general activity and spatial learning and memory. Postmortem analysis of liver function and neuroinflammation in the brain was also assessed. Our results suggest that behavior impairments resulted from the convergence of interacting metabolic alterations, made worse in a male ApoE4 mice group who also showed liver dysfunction, leading to a higher level of inflammatory cytokines in the brain. Interestingly, female ApoE4 mice on a WD revealed impairments in spatial learning and memory without the observed liver dysfunction or increase in inflammatory markers in the brain. These results suggest multiple direct and indirect pathways through which ApoE and diet-related factors interact. The striking sex difference in markers of chronic neuroinflammation in male ApoE4 mice fed the high-fat WD suggests a specific mechanism of interaction conferring significant enhanced LOAD risk for humans with the ApoE4 allele, which may differ between sexes. Additionally, our results suggest researchers exercise caution when designing and interpreting results of experiments employing a WD, being careful not to assume a WD impacts both sexes by the same mechanisms.

Perioperative complications of deep brain stimulation among patients with advanced age: a single-institution retrospective analysis.

OBJECTIVE: Deep brain stimulation (DBS) is an elective procedure that can dramatically enhance quality of life. Because DBS is not considered lifesaving, it is important that providers produce consistently good outcomes, and one factor they usually consider is patient age. While older age may be a relative contraindication for some elective surgeries, the progressive nature of movement disorders treated with DBS may suggest that older patients stand to benefit substantially from surgery. To better understand the risks of treating patients of advanced age with DBS, this study compares perioperative complication rates in patients ≥ 75 to those < 75 years old. METHODS: Patients undergoing DBS surgery for various indications by a single surgeon (May 2013-July 2019) were stratified into elderly (age ≥ 75 years) and younger (age < 75 years) cohorts. The risks of common perioperative complications and various outcome measures were compared between the two age groups using risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: A total of 861 patients were available for analysis: 179 (21%) were ≥ 75 years old and 682 (79%) were < 75 years old (p < 0.001). Patients ≥ 75 years old, compared with those < 75 years old, did not have significantly different RRs (95% CIs) of seizure (RR 0.4, 95% CI 0.1-3.3), cerebrovascular accident (RR 1.9, 95% CI 0.4-10.3), readmission within 90 days of discharge (RR 1.22, 95% CI 0.8-1.8), explantation due to infection (RR 2.5, 95% CI 0.4-15.1), or surgical revision (for lead, RR 2.5, 95% CI 0.4-15.1; for internal pulse generator, RR 3.8, 95% CI 0.2-61.7). Although the risk of postoperative intracranial bleeding was higher in the elderly group (6.1%) than in the younger group (3.1%), this difference was not statistically significant (p = 0.06). However, patients ≥ 75 years old did have significantly increased risk of altered mental status (RR 2.5, 95% CI 1.6-4.0), experiencing more than a 1-night stay (RR 1.7, 95% CI 1.4-2.0), and urinary retention (RR 2.3, 95% CI 1.2-4.2; p = 0.009). CONCLUSIONS: Although elderly patients had higher risks of certain outcome measures than younger patients, this study showed that elderly patients undergoing DBS for movement disorders did not have an increased risk of more serious complications, such as intracranial hemorrhage, infection, or readmission. Advanced age alone should not be considered a contraindication for DBS.

Promoting Health for All Kansans Through Mass Media: Lessons Learned From a Pilot Assessment of Student Ebola Perceptions.

OBJECTIVE: We aimed to assess student knowledge of Ebola virus disease (EVD) and opinions about media coverage of EVD. METHODS: We conducted a pilot study with a cross-sectional survey and a convenience sample. RESULTS: Sixty-five college students participated in the survey and reported a low level of basic knowledge of EVD, high health literacy levels, and Internet and health professionals as sources for health information. CONCLUSION: This pilot study was an important first step to understanding students' knowledge of Ebola, common sources of health information, and health literacy levels. Results from this study highlight the need to improve health communication training and further evaluate the quality of health information dissemination via all communication sources. (Disaster Med Public Health Preparedness. 2016;10:641-643).