Lisa C. Bratzke

Impact of Hypertension on Cognitive Function: A Scientific Statement From the American Heart Association.

Background—Age-related dementia, most commonly caused by Alzheimer disease or cerebrovascular factors (vascular dementia), is a major public health threat. Chronic arterial hypertension is a well-established risk factor for both types of dementia, but the link between hypertension and its treatment and cognition remains poorly understood. In this scientific statement, a multidisciplinary team of experts examines the impact of hypertension on cognition to assess the state of the knowledge, to identify gaps, and to provide future directions. Methods—Authors with relevant expertise were selected to contribute to this statement in accordance with the American Heart Association conflict-of-interest management policy. Panel members were assigned topics relevant to their areas of expertise, reviewed the literature, and summarized the available data. Results—Hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology. There is strong evidence of a deleterious influence of midlife hypertension on late-life cognitive function, but the cognitive impact of late-life hypertension is less clear. Observational studies demonstrated a cumulative effect of hypertension on cerebrovascular damage, but evidence from clinical trials that antihypertensive treatment improves cognition is not conclusive. Conclusions—After carefully reviewing the literature, the group concluded that there were insufficient data to make evidence-based recommendations. However, judicious treatment of hypertension, taking into account goals of care and individual characteristics (eg, age and comorbidities), seems justified to safeguard vascular health and, as a consequence, brain health.

Cerebrospinal Fluid Markers of Alzheimer’s Disease Pathology and Microglial Activation are Associated with Altered White Matter Microstructure in Asymptomatic Adults at Risk for Alzheimer’s Disease

BACKGROUND The immune response in Alzheimers disease (AD) involves activation of microglia which may remove amyloid-β (Aβ). However, overproduction of inflammatory compounds may exacerbate neural damage in AD. AD pathology accumulates years before diagnosis, yet the extent to which neuroinflammation is involved in the earliest disease stages is unknown. OBJECTIVE To determine whether neuroinflammation exacerbates neural damage in preclinical AD. METHODS We utilized cerebrospinal fluid (CSF) and magnetic resonance imaging collected in 192 asymptomatic late-middle-aged adults (mean age = 60.98 years). Neuroinflammatory markers chitinase-3-like protein 1 (YKL-40) and monocyte chemoattractant protein-1 (MCP-1) in CSF were utilized as markers of neuroinflammation. Neural cell damage was assessed using CSF neurofilament light chain protein (NFL), CSF total tau (T-Tau), and neural microstructure assessed with diffusion tensor imaging (DTI). With regard to AD pathology, CSF Aβ42 and tau phosphorylated at threonine 181 (P-Tau181) were used as markers of amyloid and tau pathology, respectively. We hypothesized that higher YKL-40 and MCP-1 in the presence of AD pathology would be associated with higher NFL, T-Tau, and altered microstructure on DTI. RESULTS Neuroinflammation was associated with markers of neural damage. Higher CSF YKL-40 was associated with both higher CSF NFL and T-Tau. Inflammation interacted with AD pathology, such that greater MCP-1 and lower Aβ42 was associated with altered microstructure in bilateral frontal and right temporal lobe and that greater MCP-1 and greater P-Tau181 was associated with altered microstructure in precuneus. CONCLUSION Inflammation may play a role in neural damage in preclinical AD.

A Systematic Review of Relaxation, Meditation, and Guided Imagery Strategies for Symptom Management in Heart Failure.

Background:Pain, dyspnea, fatigue, and sleep disturbance are prevalent and distressing symptoms in persons with advanced heart failure. Although many lifestyle and self-care interventions have been developed to control heart failure progression, very few studies have explored treatments exclusively for symptom palliation. Cognitive-behavioral strategies may be effective treatment for these symptoms in advanced heart failure. Objective:A systemic review was conducted to describe the effect of cognitive-behavioral strategies on pain, dyspnea, fatigue, and sleep disturbance in patients with heart failure. Methods:CINAHL, Medline, and PsychINFO were searched from inception through December 2014. Articles were selected for inclusion if they tested a cognitive-behavioral strategy using a quasi-experimental or experimental design, involved a sample of adults with heart failure, and measured pain, dyspnea, fatigue, sleep disturbance, or symptom-related quality of life. The 2 authors evaluated study quality, abstracted data elements from each study, and synthesized findings. Results:Thirteen articles describing 9 unique studies met criteria and were included in the review. Five studies tested relaxation strategies, 3 tested meditation strategies, and 1 tested a guided imagery strategy. Of the 9 studies, 7 demonstrated some improvement in symptom outcomes. Relaxation, meditation, guided imagery, or combinations of these strategies resulted in less dyspnea and better sleep compared with attention control or usual care conditions and reduced pain, dyspnea, fatigue, and sleep disturbance within treatment groups (pretreatment to posttreatment). Symptom-related quality of life was improved with meditation compared with attention control and usual care conditions and improved pre– to post–guided imagery. Conclusions:Studies exploring cognitive-behavioral symptom management strategies in heart failure vary in quality and report mixed findings but indicate potential beneficial effects of relaxation, meditation, and guided imagery on heart failure-related symptoms. Future research should test cognitive-behavioral strategies in rigorously designed efficacy trials, using samples selected for their symptom experience, and measure pain, dyspnea, fatigue, and sleep disturbance outcomes with targeted symptom measures.

Intracranial arterial four-dimensional flow is associated with metrics of brain health and Alzheimer's disease

Although cerebrovascular disease has long been known to co‐occur with Alzheimers disease (AD), recent studies suggest an etiologic contribution to AD pathogenesis. We used four dimensional (4D)‐flow magnetic resonance imaging (MRI) to evaluate blood flow and pulsatility indices in the circle of Willis. We hypothesized decreased mean blood flow and increased pulsatility, metrics indicative of poor vascular health, would be associated with cerebral atrophy and an AD cerebrospinal fluid (CSF) profile.

Evidence-Based Heart Failure Medications and Cognition

Background:The etiology of cognitive impairment in heart failure (HF) is controversial and likely multifactorial. Physicians may hesitate to prescribe evidence-based HF medication because of concerns related to potential negative changes in cognition among a population that is already frequently impaired. We conducted a study to determine if prescription of evidence-based HF medications (specifically, &bgr;-blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blocking agents, diuretics, and aldosterone inhibitors) was associated with cognition in a large HF sample. Methods:A total of 612 patients completed baseline data collection for the Rural Education to Improve Outcomes in Heart Failure clinical trial, including information about medications. Global cognition was evaluated using the Mini-Cog. Results:The sample mean (SD) age was 66 (13) years, 58% were men, and 89% were white. Global cognitive impairment was identified in 206 (34%) of the 612 patients. Prescription of evidence-based HF medications was not related to global cognitive impairment in this sample. This relationship was maintained even after adjusting for potential confounders (eg, age, education, and comorbid burden). Conclusion:Prescription of evidence-based HF medications is not related to low scores on a measure of global cognitive function in rural patients with HF.

Systematic review of prediction models for delirium in the older adult inpatient

Objective To identify existing prognostic delirium prediction models and evaluate their validity and statistical methodology in the older adult (≥60 years) acute hospital population. Design Systematic review. Data sources and methods PubMed, CINAHL, PsychINFO, SocINFO, Cochrane, Web of Science and Embase were searched from 1 January 1990 to 31 December 2016. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and CHARMS Statement guided protocol development. Inclusion criteria: age >60 years, inpatient, developed/validated a prognostic delirium prediction model. Exclusion criteria: alcohol-related delirium, sample size ≤50. The primary performance measures were calibration and discrimination statistics. Two authors independently conducted search and extracted data. The synthesis of data was done by the first author. Disagreement was resolved by the mentoring author. Results The initial search resulted in 7,502 studies. Following full-text review of 192 studies, 33 were excluded based on age criteria (<60 years) and 27 met the defined criteria. Twenty-three delirium prediction models were identified, 14 were externally validated and 3 were internally validated. The following populations were represented: 11 medical, 3 medical/surgical and 13 surgical. The assessment of delirium was often non-systematic, resulting in varied incidence. Fourteen models were externally validated with an area under the receiver operating curve range from 0.52 to 0.94. Limitations in design, data collection methods and model metric reporting statistics were identified. Conclusions Delirium prediction models for older adults show variable and typically inadequate predictive capabilities. Our review highlights the need for development of robust models to predict delirium in older inpatients. We provide recommendations for the development of such models.

Cognitive decline in the middle-aged after surgery and anaesthesia: results from the Wisconsin Registry for Alzheimer's Prevention cohort

Surgery and anaesthesia might affect cognition in middle‐aged people without existing cognitive dysfunction. We measured memory and executive function in 964 participants, mean age 54 years, and again four years later, by when 312 participants had had surgery and 652 participants had not. Surgery between tests was associated with a decline in immediate memory by one point (out of a maximum of 30), p = 0.013: memory became abnormal in 77 out of 670 participants with initially normal memory, 21 out of 114 (18%) of whom had had surgery compared with 56 out of 556 (10%) of those who had not, p = 0.02. The number of operations was associated with a reduction in immediate memory on retesting, beta coefficient (SE) 0.08 (0.03), p = 0.012. Working memory decline was also associated with longer cumulative operations, beta coefficient (SE) −0.01 (0.00), p = 0.028. A reduction in cognitive speed and flexibility was associated with worse ASA physical status, beta coefficient (SE) 0.55 (0.22) and 0.37 (0.17) for ASA 1 and 2 vs. 3, p = 0.035. However, a decline in working memory was associated with better ASA physical status, beta coefficient (SE) −0.48 (0.21) for ASA 1 vs. 3, p = 0.01.

The Role of Heart Failure, Daytime Sleepiness, and Disturbed Sleep on Cognition:

Disturbed sleep and daytime sleepiness may interfere with possible direct relationships between heart failure (HF) and cognition, yet there is limited research investigating this relationship. We aimed to investigate possible mediating roles of disturbed sleep and daytime sleepiness on the relationship between HF and selected cognitive domains among individuals with and without HF. In a cross-sectional design study, we examined the data of 841 older adults with and without HF from the Aging, Demographics, and Memory Study (ADAMS). We found individuals with HF were likely to have a higher degree of disturbed sleep and daytime sleepiness. Both disturbed sleep and daytime sleepiness were significant predictors of cognition. We found that only daytime sleepiness mediated the relationship between the presence of HF and cognitive domains, such as in attention, memory, and executive function after controlling for covariates. Interventions to improve daytime sleepiness among individuals with HF may also help improving cognition.

Derivation of a simple postoperative delirium incidence and severity prediction model

Background Delirium is an important postoperative complication, yet a simple and effective delirium prediction model remains elusive. We hypothesized that the combination of the National Surgical Quality Improvement Program (NSQIP) risk calculator for serious complications (NSQIP-SC) or risk of death (NSQIP-D), and cognitive tests of executive function (Trail Making Test A and B [TMTA, TMTB]), could provide a parsimonious model to predict postoperative delirium incidence or severity. Methods Data were collected from 100 adults (≥65yo) undergoing major non-cardiac surgery. In addition to NSQIP-SC, NSQIP-D, TMTA and TMTB, we collected participant age, sex, ASA score, tobacco use, type of surgery, depression, Framingham risk score, and preoperative blood pressure. Delirium was diagnosed with the Confusion Assessment Method (CAM), and the Delirium Rating Scale-R-98 (DRS) was used to assess symptom severity. LASSO and Best Subsets logistic and linear regression were employed in line with TRIPOD guidelines. Results Three participants were excluded due to intraoperative deaths (2) and alcohol withdrawal (1). Ninety-seven participants with a mean age of 71.68±4.55, 55% male (31/97 CAM+, 32%) and a mean Peak DRS of 21.5±6.40 were analyzed. Of the variables included, only NSQIP-SC and TMTB were identified to be predictors of postoperative delirium incidence (p<0.001, AUROC 0.81, 95% CI: 0.72, 0.90) and severity (p<0.001, Adj. R2: 0.30). Conclusions In this cohort, preoperative NSQIP-SC and TMTB were identified as predictors of postoperative delirium incidence and severity. Future studies should verify whether this two-factor model could be used for accurate delirium prediction.Background: Delirium is an important postoperative complication, yet a simple and effective delirium prediction model remains elusive. We hypothesized that the combination of the National Surgical Quality Improvement Program (NSQIP) risk calculator for serious complications (NSQIP-SC) or risk of death (NSQIP-D), and cognitive tests of executive function (Trail Making Test A and B [TMTA, TMTB]), could provide a parsimonious model to predict postoperative delirium incidence or severity. Methods: Data were collected from 100 adults (>65yo) undergoing major non-cardiac surgery. In addition to NSQIP-SC, NSQIP-D, TMTA and TMTB, we collected participant age, sex, ASA score, tobacco use, type of surgery, depression, Framingham risk score, and preoperative blood pressure. Delirium was diagnosed with the Confusion Assessment Method (CAM), and the Delirium Rating Scale-R-98 (DRS) was used to assess symptom severity. LASSO and Best Subsets logistic and linear regression were employed in line with TRIPOD guidelines. Results: Three participants were excluded due to intraoperative deaths (2) and alcohol withdrawal (1). Ninety-seven participants with a mean age of 71.68+4.55, 55% male (31/97 CAM+, 32%) and a mean Peak DRS of 21.5+6.40 were analyzed. Of the variables included, only NSQIP-SC and TMTB were identified to be predictors of postoperative delirium incidence (p<0.001, AUROC 0.81, 95% CI: 0.72, 0.90) and severity (p<0.001, Adj. R2: 0.30). Conclusions: In this cohort, preoperative NSQIP-SC and TMTB were identified as predictors of postoperative delirium incidence and severity. Future studies should verify whether this two- factor model could be used for accurate delirium prediction. Keywords: aging, delirium, perioperative, prediction, surgical risk. Clinical Trial Registration ID #NCT03124303 and #NCT01980511

Self-Management in Liver Transplant Recipients: A Narrative Review

Introduction: Although self-management is essential for liver transplant recipients, there is no review that has synthesized findings related to self-management in this population. Objective: This narrative review aimed to synthesize the current findings and identify the gaps in knowledge about self-management in liver recipients. Methods: A search of PubMed, CINAHL Plus, PsychINFO, ProQuest, and Web of Science was conducted using the following terms: [Self-care OR Self-management OR Health behavior] AND [Liver transplantation]. Peer-reviewed published research articles focusing on self-management of adult recipients were selected. A total of 23 articles were included for review. Two reviewers independently reviewed the full text of selected articles and extracted the data about definitions, measurements, and findings regarding self-management. Results: Three areas of self-management were identified, including medication nonadherence (n = 11), alcohol recidivism (n = 11), and health maintenance (n = 5). Reported rates of medication nonadherence ranged from 8% to 66%. Medication nonadherence was related to recipients’ demographic (eg, age or sex), transplant-related (eg, time since transplant), and pretransplant variables (eg, history of substance/alcohol abuse). Reported alcohol recidivism rates ranged from 3% to 95%. Age, pretransplant variables (eg, abstinent time before transplant), and personality disorder were identified to be related to alcohol recidivism after transplant. The health maintenance studies discussed behaviors such as smoking, clinic appointment attendance, or vaccination/health screening behaviors of recipients. Discussion: Self-management studies in liver recipients have been narrowly focused on medication nonadherence and alcohol recidivism. To improve self-management in recipients, self-management beyond medication nonadherence and alcohol recidivism should be comprehensively examined.