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Background: Florbetapir F 18 (F-AV-45) is a positron emission tomography imaging ligand for the detection of amyloid aggregation associated with Alzheimer disease. Earlier data showed that florbetapir F 18 binds with high affinity to β-amyloid (Aβ) plaques in human brain homogenates (Kd=3.7 nM) and has favorable imaging pharmacokinetic properties, including rapid brain penetration and washout. This study used human autopsy brain tissue to evaluate the correlation between in vitro florbetapir F 18 binding and Aβ density measured by established neuropathologic methods.Methods: The localization and density of florbetapir F 18 binding in frozen and formalin-fixed paraffin-embedded sections of postmortem brain tissue from 40 patients with a varying degree of neurodegenerative pathology was assessed by standard florbetapir F 18 autoradiography and correlated with the localization and density of Aβ identified by silver staining, thioflavin S staining, and immunohistochemistry.Results: There were strong quantitative correlations between florbetapir F 18 tissue binding and both Aβ plaques identified by light microscopy (Silver staining and thioflavin S fluorescence) and by immunohistochemical measurements of Aβ using 3 antibodies recognizing different epitopes of the Aβ peptide. Florbetapir F 18 did not bind to neurofibrillary tangles.Conclusions: Florbetapir F 18 selectively binds Aβ in human brain tissue. The binding intensity was quantitatively correlated with the density of Aβ plaques identified by standard neuropathologic techniques and correlated with the density of Aβ measured by immunohistochemistry. As Aβ plaques are a defining neuropathologic feature for Alzheimer disease, these results support the use of florbetapir F 18 as an amyloid positron emission tomography ligand to identify the presence of Alzheimer disease pathology in patients with signs and symptoms of progressive late-life cognitive impairment. [ABSTRACT FROM AUTHOR]

Abstract: Regardless of early invasive or ischemia-guided approaches to non-ST segment elevation myocardial infarction (NSTEMI) management, P2Y 12 inhibitors remain the backbone in therapy. The ideal timing of administration remains unclear. The purpose of this study was to determine the safety and effectiveness of early versus late administration of P2Y 12 inhibitors in patients presenting with an NSTEMI who go to the catheterization laboratory beyond 24 hours from presentation. We performed a single center, retrospective cohort study. Patients were classified into groups depending on whether they received early versus late administration of a P2Y 12 inhibitor. The primary outcome was the rate of major and clinically relevant, nonmajor bleeding (CRNMB). Secondary outcomes included troponin peak and length of stay after cardiac catheterization. Of the 121 patients included, 53 patients were in the early and 68 patients were in the late group. The number of bleeding events were similar between both groups ( P = 1.00). There were 3 (5.7%) major bleeding events in the early group and 5 (7.4%) bleeding events in the late group. There were 5 (9.4%) CRNMB events in the early group and 6 (8.8%) CRNMB events in the late group. There was a significant difference in troponin peak, 4.56 ng/mL in the early group and 1.77 ng/mL in the late group ( P = 0.02). The rate of bleeding did not differ between patients who received early or late administration of P2Y 12 inhibitors for NSTEMI management who undergo delayed cardiac catheterization., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mastering clinical judgment (CJ) skills is an essential competency for nurses in all health care environments., Problem: Complexities of the health environment combined with the intricacies of nursing practice can pose potential risks to client safety., Approach: Over a 2-year period, a 3-phased approach using (1) survey results from nurses in education and practice, (2) discussion forums, and (3) a series of think tanks that comprised nurse educators resulted in the development of the Guide for CJ., Outcomes: The Guide for CJ provides nurse educators with an evidence-based resource to promote CJ skills in nursing students. The environmental and individual factors and expected nurse responses and behaviors contained in the Guide are well-aligned with the cognitive operations contained in the National Council of State Boards of Nursing Action Model., Conclusions: Educators may use the Guide to support faculty development and operationalize CJ to develop a variety of learning strategies for use in multiple learning environments., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Incivility among nursing faculty and administrators lowers morale, damages relationships, and threatens workplace health and productivity., Purpose: This national study examined nursing faculty and administrators' perceptions of civility and incivility in nursing education, ways to address the problem, and psychometric properties of the Workplace Incivility/Civility Survey (WICS)., Methods: A convergent mixed-methodological study was used to conduct the study. A factor analysis and other reliability analyses were conducted on the WICS., Results: Respondents included 1074 faculty and administrators who identified types and frequency of incivility, severity and contributors to the problem, reasons for avoiding incivility, and strategies to improve civility. Eight themes of uncivil behaviors were garnered. The WICS was shown to be a psychometrically sound instrument to measure civility and incivility., Conclusion: This study reported faculty and administrators' perceptions of civility and incivility in nursing education and provided evidence-based strategies to prevent and address the problem., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

This article discusses skill proficiency of providers related to emergency cricothyroidotomies. Various techniques to improve procedural skills were studied. Accurate identification of the cricothyroid membrane via palpation remained consistently inadequate. High-fidelity simulation including the use of human cadavers may be the preferred method of skill training for crisis management. The authors emphasize that additional research is needed regarding a method for rapid cricothyroid membrane identification as well as needle cricothyroidotomy versus surgical airway on cadavers. More consistent training will enable emergency care providers to perform this rare but lifesaving skill., Competing Interests: The authors have no conflicts of interest or financial disclosures to declare., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Incivility and disrespect in health care weaken teamwork and collaboration, diminish communication, and can impact an individual's ability and willingness to speak up and advocate for patient care., Problem: Evidence-based teaching strategies are needed to prepare nursing students to address incivility in academic and practice settings., Approach: The authors describe a virtual learning experience designed to prepare students to prevent and address incivility in academic and health care environments and report preliminary assessment data from student users., Outcomes: More than 90% of 22 000 student respondents indicated they were satisfied with the learning experience, were made aware of the consequences of incivility and its effects on patient safety, and planned to apply techniques for addressing incivility into their nursing practice CONCLUSION: Civility mentor is effective in educating students about the consequences of incivility, developing skills to foster civility, communicating more assertively, and addressing incivility in academic and health care environments.

Background: Civility, psychological safety, and effective stress management are essential for meaningful learning conversations., Problem: Incivility triggers fear and humiliation, impairs clinical judgment and learning, reduces psychological safety, and increases cognitive load. These factors converge to make learners less likely to incorporate feedback, speak up when there is a problem, and discuss practice errors and patient safety issues., Approach: The authors combined the Basic Assumption and the PAAIL (Preview, Advocacy1, Advocacy2, Inquiry, and Listen) conversational strategy to help surface (rather than obscure) both educators' and learners' thinking. The synergy of these 2 strategies allows educators to identify individual learning needs and develop the learners' clinical judgment skills. This process improves learning by reducing incivility and cognitive load, improving psychological safety, and strengthening clinical judgment skills., Conclusion: This conversational strategy can minimize stress and anxiety in learners and optimize learning.

Purpose: Exercise intervention studies for brain health can be difficult to interpret due to heterogeneity in exercise intensity, exercise duration, and in adherence to the exercise intervention. This study aimed to characterize heterogeneity in these components in a cohort of healthy middle-age and older adults who participated in a prescribed 6-month supervised aerobic exercise intervention as part of the Brain in Motion study., Methods and Results: Group-based multitrajectory analysis (GBMTA) was used to characterize variation in the trajectory of exercise intensity and duration for male and female participants in the first 3 months of the exercise program. The GBMTA for males and females revealed two distinct trajectory subgroups, namely, "high-increasing" (HI) and "low-increasing" (LI). Logistic regression was used to assess the association between the identified latent subgroups and (i) demographic characteristics; (ii) physiological characteristics, including cardiovascular and cerebrovascular function; (iii) genetic characteristics; and (iv) adherence with American College of Sports Medicine guidelines on exercise for older adults. Of the 196 participants, 54.1% met the American College of Sports Medicine aerobic exercise targets for intensity and duration during the intervention. Aerobic fitness (maximal oxygen uptake; odds ratio, 1.27; P < 0.01) was significantly different between these trajectory subgroups in males, and cerebrovascular function (cerebrovascular resistance; odds ratio, 0.14; P < 0.01) was significantly different between these trajectory subgroups in females., Conclusion: This novel approach to tracking a prespecified exercise program highlights that there are individual and group-specific variations within a prescribed exercise intervention. Characterizing exercise adherence in this way holds promise in developing optimized exercise prescriptions tailored to individual baseline characteristics, and additionally highlighting those participants at greatest risk of not meeting minimum dosage requirements for physiological and/or cognitive health.

Background: Nurses have a professional and ethical obligation to foster civility and healthy work environments to protect patient safety. Evidence-based teaching strategies are needed to prepare nursing students to address acts of incivility that threaten patient safety., Problem: Incivility in health care must be effectively addressed because the delivery of safe patient care may depend on these vital skills., Approach: Cognitive rehearsal (CR) is an evidence-based technique where learners practice addressing workplace incivility in a nonthreatening environment with a skilled facilitator. The author describes the unique combination of CR, simulation, evidence-based scripting, deliberate practice, and debriefing to prepare nursing students to address uncivil encounters., Outcomes: Learners who participated in CR identified benefits using this approach., Conclusions: Combining CR with simulation, evidence-based scripting, repeated dosing through deliberate practice, and skillful debriefing is an effective method to provide nursing students with the skills needed to address incivility, thereby increasing the likelihood of protecting patient safety.

Accelerated trajectories of cognitive decline in older adults may increase the risk of developing Alzheimer disease and related dementias (ADRD). Physical activity has potential modifying effects on these changes that could prevent or delay ADRD. This review explores the hypothesis that multiple, mutually complimentary, and interacting factors explain the positive association between exercise and the optimization of cognition in older adults.

Professional practice models (PPMs) are an integral part of any organization on the Magnet® journey, whether initial designation or redesignation. Through the journey, the PPM should become embedded within the nursing culture. Leadership at multiple levels is crucial to ensure successful adoption and implementation.

This article presents an evidence-based approach to integrate concepts of civility, professionalism, and ethical practice into nursing curricula to prepare students to foster healthy work environments and ensure safe patient care. The author provides evidence to support this approach and includes suggestions for new student orientation, strategies for the first day of class, exemplars for incorporating active learning strategies to enhance student engagement, an emphasis on positive faculty role modeling, and suggestions for curricular integration.

Although incivility in higher education has been widely described, little evidence exists regarding incivility among health professions students in online environments. This study aims to integrate literature on cybercivility in health professions education. The extent to which health professions students and faculty experience cyberincivility, the direct and indirect effects and actions taken after cyberincivility, and themes that guide facilitation of cybercivility are discussed. Efforts to prevent cyberincivility can be achieved through focused education on cybercivility, development of clear policies related to its consequences, and formulation of guidelines for both student and faculty behavior online.

Academic incivility can increase student stress, jeopardize learning, damage relationships, and negatively impact the academic environment. This 3-year longitudinal study measured a cohort of prelicensure nursing students' progressive perceptions of stress, coping, student-student and faculty-student relationships, and levels of academic civility. While civility scores remained mild to moderately high overall, there was a slightly declining trend over the 3-year period. Perceived stressors and coping strategies and ways to improve academic civility are identified and discussed.

Faculty incivility can have lasting and devastating effects on individuals and organizations, including low morale, high turnover, increased absenteeism, isolation and alienation, diminished quality of work, and increased illness and health issues. To assess the nature and impact of faculty-to-faculty incivility, the author discusses a national study, its outcomes, and several evidence-based strategies to affectively address the problem.

The appeal of online learning has increased dramatically among nurses who are pursuing higher-education opportunities. However, online learning has created potential avenues for uncivil behaviors that can affect student satisfaction, performance, and retention. This is the second of 2 articles detailing a study to empirically measure nursing faculty and student perceptions of an online learning environment (OLE). Part 1, in the July/August 2012 issue, described the quantitative results including the types and frequency of uncivil behaviors and the extent to which they are perceived to be a problem in online courses. In this portion of the study, the authors discuss the qualitative findings, including the challenges and advantages of the OLE, specific ways to foster civility, and strategies to promote student success and retention.

Online learning has created another potential avenue for incivility. Cyber-bullying, a form of incivility that occurs in an electronic environment, includes posting rumors or misinformation, gossiping, or publishing materials that defame and humiliate others. This is the first of 2 articles detailing a study to empirically measure nursing faculty and student perceptions of incivility in an online learning environment (OLE). In this article, the authors discuss the quantitative results including the types and frequency of uncivil behaviors and the extent to which they are perceived to be a problem in online courses. Part 2 in the September/October issue will describe challenges and advantages of the OLE, discuss specific ways to foster civility, and present strategies to promote student success and retention.

Incivility in healthcare can lead to unsafe working conditions, poor patient care, and increased medical costs. The authors discuss a study that examined factors that contribute to adverse working relationships between nursing education and practice, effective strategies to foster civility, essential skills to be taught in nursing education, and how education and practice can work together to foster civility in the profession.

Student incivility is defined as rude and disruptive behavior that, when left unaddressed, may spiral into aggressive or violent behavior. Nursing faculty are challenged by uncivil student behavior and many are underprepared to deal with its effects. Some faculty members consider leaving nursing education because of the serious toll that incivility often takes on their personal and professional lives. The impact of student incivility on faculty is especially troubling during a national nursing shortage. The author provides nursing faculty with several ready-to-use strategies for preventing and effectively dealing with student incivility in nursing education.

Introduction: The Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) was modified for use in mild cognitive impairment (MCI) trials and tested in the ADCS MCI randomized clinical trial of donepezil, vitamin E, and placebo. We assessed feasibility for its use by determining whether or not: (1) it distinguished a medication effect at 6 months and 12 months, (2) baseline demographic or clinical characteristics predicted change, (3) there was an association between MCI-CGIC and change in other clinical measures in order to evaluate external or concurrent validity., Methods: We used a generalized estimating equations approach for ordinal outcome data to test the effects of treatment, baseline characteristics, and change in clinical measures on the MCI-CGIC over 12 months, and ordinal logistic regression to assess the association between MCI-CGIC and change in clinical measures at 6 months and 12 months., Results: On the MCI-CGIC overall, 12.9% and 10.6% were rated as having improved, and 31.6% and 39.8% as having worsened over 6 months and 12 months, respectively. The MCI-CGIC did not distinguish the donepezil or vitamin E groups from placebo at 6 and 12 months treatment. Variables at screening or baseline that were associated with worse CGIC scores over 6 and 12 months included white race, greater years of education, worse depression, dementia severity rating, cognitive, and daily activities scores, and lower memory domain scores on a neuropsychological battery. Rate of worsening on the MCI-CGIC over 12 months was associated with change on the Alzheimer Disease Assessment Scale-cognitive and on executive function. Worsening at 6 months and 12 months, separately, were associated with the corresponding change in Alzheimer Disease Assessment Scale-cognitive, Activities of Daily Living, Beck Depression Inventory, Mini-Mental State Examination, Clinical Dementia Rating sum of boxes, memory, and executive function., Conclusions: Change detected by the MCI-CGIC was associated with baseline clinical severity and with change in clinical ratings over 6 and 12 months, supporting the validity of a CGIC approach in MCI. The effect size of the donepezil-placebo difference was similar to that of other outcomes at 12 months. About 40% of MCI patients were judged worse and about 11% improved, consistent with clinical experience and other ratings.

Objective: To measure clinically relevant change in Alzheimer disease (AD) using a family member-completed Dementia Severity Rating Scale (DSRS) questionnaire., Background: Measuring rate of change provides important clinical information. Most neuropsychologic scores change nonlinearly, complicating their use as a predictor of change throughout the illness., Methods: DSRS and Mini Mental State scores were prospectively collected on 702 patients with AD from first evaluation until they became too impaired to return to clinic., Results: DSRS score increased an average of 4.48 points/y [95% confidence interval (CI): 4.14-4.82] throughout the entire range of severity. In contrast, the Mini Mental State declined an average of 2.15 points/y (95% CI: 1.85-2.46) during the first 2 years, accelerated to 3.83 points/y (95% CI: 3.28-4.38) during the subsequent 3 years, and then slowed to an annual decline of 1.63 points during the last 2 years (95% CI: 0.21-3.05). A younger age of symptom onset was associated with an increased rate of DSRS change (P=0.03)., Conclusions: The DSRS provides a clinical measure of functional impairment in AD that increases about 4.48 points/y from the earliest symptomatic stage until patients become too severely impaired to return to clinic.

Nursing students who demonstrate disruptive and at-risk behaviors in the classroom and clinical arena compromise the learning environment and are unable to provide safe, quality client care. They require early and swift identification, consultation, sanctions, or possible referral into treatment to protect themselves and public safety. The authors describe the evolution of a comprehensive policy for faculty intervention with at-risk students and provide an exemplar of a situation illustrating the use of the policy.

Objective: To determine the utility of 8,12-isoprostaneF2alpha-VI (iP), a specific and sensitive index of lipid peroxidation, as a biomarker for dementia in Parkinson disease (PD)., Background: iP is a member of the F2-isoprostanes family that has been shown to be promising biomarker for Alzheimer disease. However, iP levels have not been studied in patients with clinical diagnosis of PD or Parkinson disease with dementia (PDD)., Methods: PD and PDD patient plasma and urine iP levels were compared with age-matched and sex-matched controls. Clinical measures including demographics and tests of motor function, affect, and cognition were assessed and compared with iP levels., Results: There were no differences in plasma iP levels between PD subjects and controls (299 vs. 306 pg/mL; P=0.6). Urine iP levels were higher in cases than controls (2.8 vs. 2.1 ng/mg Cr; P=0.003), but levels were lower than those seen in Alzheimer disease patients in prior studies. Within PD subjects, there was no association of iP levels in either the plasma or urine with performance on any clinical measure., Conclusions: Plasma and urine iP levels do not seem to be substantially elevated in PD and are not associated with severity of cognitive impairment in PDD.

Objective: To evaluate the diagnostic value of CSF biomarkers in patients with known pathology due to frontotemporal lobar degeneration (FTLD)., Background: It is important to distinguish FTLD from other neurodegenerative diseases like Alzheimer disease (AD), but this may be difficult clinically because of atypical presentations., Methods: Patients with FTLD (n = 30) and AD (n = 19) were identified at autopsy or on the basis of genetic testing at University of Pennsylvania and Erasmus University Medical Center. CSF was obtained during a diagnostic lumbar puncture and was analyzed using assays for total tau and amyloid-beta 1-42 (A beta(42)). Patients also were assessed with a brief neuropsychological battery., Results: CSF total tau level and the ratio of CSF total tau to A beta(42) (tau/A beta(42)) were significantly lower in FTLD than in AD. Receiver operating characteristic curve analyses confirmed that the CSF tau/A beta(42) ratio is sensitive and specific at discriminating between FTLD and AD, and is more successful at this than CSF total tau alone. Although some neuropsychological measures are significantly different in autopsy-proven FTLD and AD, combining these neuropsychological measures with CSF biomarkers did not improve the ability to distinguish FTLD from AD., Conclusions: The ratio of CSF tau/A beta(42) is a sensitive and specific biomarker at discriminating frontotemporal lobar degeneration from Alzheimer disease in patients with known pathology.

Background: Mutations in the LRRK2 gene are an important cause of familial and nonfamilial parkinsonism. Despite pleomorphic pathology, LRRK2 mutations are believed to manifest clinically as typical Parkinson disease (PD). However, most genetic screens have been limited to PD clinic populations., Objective: To clinically characterize LRRK2 mutations in cases recruited from a spectrum of neurodegenerative diseases., Methods: We screened for the common G2019S mutation and several additional previously reported LRRK2 mutations in 434 individuals. A total of 254 patients recruited from neurodegenerative disease clinics and 180 neurodegenerative disease autopsy cases from the University of Pennsylvania brain bank were evaluated., Results: Eight cases were found to harbor a LRRK2 mutation. Among patients with a mutation, two presented with cognitive deficits leading to clinical diagnoses of corticobasal syndrome and primary progressive aphasia., Conclusion: The clinical presentation of LRRK2-associated neurodegenerative disease may be more heterogeneous than previously assumed.

Objective: To investigate the clinical features of autopsy-proven corticobasal degeneration (CBD)., Methods: We evaluated symptoms, signs, and neuropsychological deficits longitudinally in 15 patients with autopsy-proven CBD and related these observations directly to the neuroanatomic distribution of disease., Results: At presentation, a specific pattern of cognitive impairment was evident, whereas an extrapyramidal motor abnormality was present in less than half of the patients. Follow-up examination revealed persistent impairment of apraxia and executive functioning, worsening language performance, and preserved memory. The motor disorder emerged and worsened as the condition progressed. Statistical analysis associated cognitive deficits with tau-immunoreactive pathology that is significantly more prominent in frontal and parietal cortices and the basal ganglia than temporal neocortex and the hippocampus., Conclusion: The clinical diagnosis of corticobasal degeneration should depend on a specific pattern of impaired cognition as well as an extrapyramidal motor disorder, reflecting the neuroanatomic distribution of disease in frontal and parietal cortices and the basal ganglia.

Objective: To evaluate the feasibility of longitudinal assessment and the psychometric properties of both established and new outcome measures used in clinical trials of patients with dementia in a cohort of Spanish-speaking elders in the United States., Methods: This is a prospectively collected multicenter study comparing patients with Alzheimer disease (AD) (N=77) and elderly controls (N=17) who are primary Spanish speakers. Spanish-speaking individuals with AD (SSI AD) were selected to represent predefined categories of impairment as determined by a Mini-Mental State Examination score. Controls were selected to approximately match by age and education (SSI C). Subjects were administered a series of Spanish translations of established outcome measures (Mini-Mental State Examination, Clinical Dementia Rating, Geriatric Dementia Scale), and Functional Assessment Staging (FAST)] and new outcome measures developed for United States in clinical trials to assess cognition, function, behavioral disturbance, and clinical global change. Half of the subjects were assessed at 1 and 2 months to evaluate reliability; all subjects were assessed at 6 and 12 months. Comparisons were made between patients and controls and between the Spanish-speaking cohort and a similar English-speaking cohort., Results: The 12-month completion rate was 77%, with a trend toward greater impairment in those with full retention. Both established and new measures demonstrated good internal consistency and test-retest reliability in this cohort. All but one measure of cognition demonstrated excellent discriminability between AD subjects and controls. The SSI AD cohort declined significantly on measures of cognition, function, and clinical global change over the 12-month assessment period. The SSI AD and English AD (ESI AD) cohorts declined equivalently on the most common outcomes in clinical trials of AD (delayed recall, clinical global change). Likewise, the most common behavioral changes were also similar in the ESI and SSI groups. However, the annual change was lower in SSI AD than in the ESI AD on several other measures of cognition and function., Conclusions: These results support the recruitment of Spanish-speaking patients and the use of Spanish language translations for use in the clinical trials for AD.

Background: Because primary prevention trials will require large samples and modest treatment effects are expected, the use of standard clinician-administered, clinic-based measures are unlikely to be feasible. There is a need for proxy-administered outcome measures. The goal of the Alzheimer's Disease Cooperative Study (ADCS) Prevention Instrument Project was to conduct a simulated Alzheimer disease prevention trial in 650 nondemented elderly (Ferris et al, 2006). This involved comparison of data acquisition from both home and clinic and the use of both informant-ratings and self-ratings. Important outcomes included clinical global impressions of change (CGIC) as indicators of clinically meaningful change. Such ratings provide verification that the effects of a medication as measured on rating scales are readily observable and clinically meaningful. One objective was to develop self-rated and study partner-rated CGICs optimized for nondemented elderly or people with very early Alzheimer disease. An important consideration was whether global assessments are specific and sensitive measures of change during a prevention trial., Methods: A self-administered CGIC and a study partner-rated CGIC were developed to be used either in the clinic or at home. Using 3-month follow-up data, we determined its reliability and validity with 317 subject-partner pairs. We compared subject-ratings with partner-ratings, clinic-based with home-based ratings, and ratings based on severity as determined by the Clinical Dementia Rating scale., Results: There were no differences between clinic and home ratings. Overall, 24% of subjects rated themselves, and 10% of study partners rated the subjects, as minimally to markedly improved. Subjects and partners agreed to within 1 point of their ratings 83% of the time on the 7-point scale. There were weak correlations, generally <0.20, with change scores of selected clinical rating scales., Discussion: The CGICs behaved as expected, showing no overall change over 3 months, no difference between administrations at home compared with clinics, and concurrent validity. Some subjects tended to rate themselves better than their partners rated them. These analyses show the potential for using home-based CGICs which can be completed with minimal supervision and allow assessments of potential preventative interventions.

Three hundred forty-two subjects underwent 428 research lumbar punctures for studies of cerebrospinal fluid (CSF) biomarkers. Subjects were 67 Alzheimer disease or mild cognitive impairment (AD/MCI) patients and 275 cognitively normal adults aged 21 to 88. Lumbar puncture was performed in the lateral decubitus or sitting position using the Sprotte 24 g atraumatic spinal needle. Up to 34 ml of cerebrospinal fluid were collected. Anxiety and pain experienced during lumbar puncture were rated on a visual analog scale. The frequency of any adverse event (11.7%), clinically significant adverse events (3.97%), and typical post-lumbar puncture headache (PLPHA) (0.93%) was low. Risk of post-lumbar puncture headache was unrelated to age, gender, position during lumbar puncture, ml of cerebrospinal fluid collected, or minutes of recumbent rest following lumbar puncture. The frequency of post-lumbar puncture headache was lower in AD/MCI (P = 0.03) than any other subject group. Anxiety and pain ratings were low. Younger subjects reported more anxiety than old (P = 0.001) and AD/MCI subjects (P = 0.008) and more pain than older normal subjects (P = 0.013). Pain ratings for women were higher than those for men (P = 0.006). Using the Sprotte 24 g spinal needle, research lumbar puncture can be performed with a very low rate of clinically significant adverse events and with good acceptability in cognitively impaired persons and cognitively normal adults of all ages.

Type 2 diabetes is a worldwide epidemic. Cardiovascular diseases remain the major cause of death in patients with diabetes, partly because of the association of diabetes and the metabolic syndrome. In this review, we will discuss the evidence for treatment and prevention of cardiovascular diseases in patients with diabetes. Aggressive treatment of hypertension and dyslipidemia is at the cornerstone in the management of heart disease in those patients. Despite its known benefit on the prevention of the microvascular complications of diabetes, intensive glycemic control may or may not have a significant effect on reducing macrovascular diseases. Finally, lifestyle changes and other cardiovascular therapies aimed at preventing heart disease may also prevent or delay the development of diabetes.

Objective: To quantify the isoprostane 8,12-iso-iPF2alpha-VI in brain tissues obtained from patients with AD, patients with frontotemporal dementia (FTD), and controls., Background: Enhanced brain oxidative stress with secondary damage to cellular macromolecules may play a role in the pathogenesis of AD and FTD. The isoprostane 8,12-iso-iPF2alpha-VI is a specific and sensitive marker of in vivo lipid peroxidation and is increased in AD., Methods: Levels of this isoprostane were determined by gas chromatography/negative ion chemical ionization mass spectrometry., Results: Levels of 8,12-iso-iPF2alpha-VI were markedly elevated in both frontal and temporal cortex of AD brains compared to the corresponding areas of FTD and controls. No significant difference in brain 8,12-iso-iPF2alpha-VI levels for any regions considered was observed between FTD and controls., Conclusions: Lipid peroxidation is a feature of AD, but not FTD. The generation of 8,12-iso-iPF(2alpha)-VI in the brain is not a general or final common pathway of neurodegeneration, but may be relatively specific for disease processes in AD and not FTD.

Objective: To assess relations between discrete visual perceptual functions commonly affected in patients with neurodegenerative dementia and the performance of instrumental activities of daily living (IADL)., Background: Neuropsychologic measures are often used to predict IADL performances in dementia patients. Prior studies have focused on the contribution of higher-level memory and executive deficits to IADL. The relation between visuoperceptual dysfunction and IADL has not been studied systematically., Methods: Thirty-five elderly patients with neurodegenerative disorders, most diagnosed with probable Alzheimer disease, participated. Patients completed tasks tapping visual perceptual functions believed to be mediated by occipital lobe structures (shape discrimination), posterior inferotemporal regions (face, object form, and written word discrimination), and the dorsolateral parietal lobe (spatial localization). A knowledgeable caregiver rated IADL performance., Results: Object form discrimination, but not other visual perceptual functions, correlated significantly ( = 0.60) with performances of visually based IADL (e.g., misjudging distances, driving, and recognizing familiar people), but not with other IADL, when the variance attributable to dementia severity, language disturbance, and other visual perceptual abilities was controlled., Conclusions: In contrast to prior investigations that have focused primarily on relations of memory and executive control deficits with IADL in neurologically impaired patients, the results of this study highlight the important contribution of bilateral inferotemporal visual perceptual systems for the performance of IADL in elderly patients with neurodegenerative dementia.

This study was designed to determine whether Alzheimer disease (AD) caregivers view the benefits of hospice as more relevant to themselves or to patients, to identify the features of hospice care that are most important to caregivers, and to determine how often these features are described in hospice promotional materials. Telephone interviews were conducted with AD caregivers from a Memory Disorders Clinic of an urban academic medical center (N = 45). A nationwide mail survey of randomly selected hospices was also conducted (N = 66). Caregivers were twice as likely to say that hospice would benefit them than they were to say it would benefit the patient (26 vs. 13; p = 0.002). The features of hospice that were most important to caregivers were continued follow-up evaluation by the patient's primary care provider and hospice's emphasis on helping patients to avoid hospital admission. The least important was the availability of a chaplain. There was moderate agreement between the importance of various hospice features to caregivers, and the representation of that feature in hospice promotional materials. AD caregivers have generally positive opinions about hospice's benefits for themselves. In discussing hospice with AD caregivers, clinicians may want to emphasize selected features of hospice that are particularly important to caregivers.

Background: Dementia is a frequent complication of idiopathic parkinsonism or PD, usually occurring later in the protracted course of the illness. The primary site of neuropathologic change in PD is the substantia nigra, but the neuropathologic and molecular basis of dementia in PD is less clear. Although Alzheimer's pathology has been a frequent finding, recent advances in immunostaining of alpha-synuclein have suggested the possible importance of cortical Lewy bodies (CLBs) in the brains of demented patients with PD., Methods: The brains of 22 demented and 20 nondemented patients with a clinical and neuropathologic diagnosis of PD were evaluated with standard neuropathologic techniques. In addition, CLBs and dystrophic neurites were identified immunohistochemically with antibodies specific for alpha-synuclein and ubiquitin; plaques and tangles were identified by staining with thioflavine S. Associations between dementia status and pathologic markers were tested with logistic regression., Results: CLBs positive for alpha-synuclein are highly sensitive (91%) and specific (90%) neuropathologic markers of dementia in PD and slightly more sensitive than ubiquitin-positive CLBs. They are better indicators of dementia than neurofibrillary tangles, amyloid plaques, or dystrophic neurites., Conclusion: CLBs detected by alpha-synuclein antibodies in patients with PD are a more sensitive and specific correlate of dementia than the presence of Alzheimer's pathology, which was present in a minority of the cases in this series.

Objective: To assess the efficacy of lamotrigine, a novel antiepileptic drug that inhibits glutamate release, to retard disease progression in Huntington disease (HD)., Background: Excitatory amino acids may cause selective neuronal death in HD, and lamotrigine may inhibit glutamate release in vivo., Methods: A double-blinded, placebo-controlled study was conducted of 64 patients with motor signs of less than 5 years' duration who were randomly assigned to either placebo or lamotrigine and assessed at 0 (baseline), 12, 24, and 30 months. The primary response variable was total functional capacity (TFC) score. Secondary response variables included the quantified neurological examination and a set of cognitive and motor tests. Repeated fluorodeoxyglucose measurements of regional cerebral metabolism using PET also were included., Results: Fifty-five patients (28 on lamotrigine, 27 on placebo) completed the study. Neither the primary response variable nor any of the secondary response variables differed significantly between the treatment groups. Both the lamotrigine and the placebo group deteriorated significantly on the TFC, in the lamotrigine group by 1.89 and the placebo group by 2.11 points. No effect of CAG size on the rate of deterioration could be detected., Conclusions: There was no clear evidence that lamotrigine retarded the progression of early Huntington disease over a period of 30 months. However, more patients on lamotrigine reported symptomatic improvement (53.6 versus 14.8%; p = 0.006), and a trend toward decreased chorea was evident in the treated group (p = 0.08). The study also identified various indices of disease progression, including motor tests and PET studies, that were sensitive to deterioration over time.

During the past 10 years, there has been a rapidly growing number of pharmaceutical industry-sponsored drug trials for treatment of Alzheimer disease (AD) and other neurodegenerative diseases. As public awareness and concerns about AD have grown, so has interest in developing drug therapies for retarding symptom progression, delaying onset, and ultimately curing the disease. Ethical debate on the use of placebo control trials in AD research has come of age in the United States with the availability of treatments approved by the Food and Drug Administration. The experts and the public agree that more effective therapies are necessary, and new therapeutic options are being developed as rapidly as possible. The arguments on each side of the debate are provocative and important but do not provide unequivocal justification for either the abandonment or the maintenance of placebo-controlled trials in all AD research. Clinical trials differ with respect to scientific and practical goals, and these factors inherently affect the ethical priorities of each study. We present these contrasting points of view to delineate some of the issues rather than to make specific recommendations other than to urge that all clinical trials in AD should be designed with careful consideration of the ethical issues surrounding the use of placebo controls. As new and more effective treatments emerge, the ethical framework for placebo use in AD studies will require frequent re-examination. To make wise choices, patients, caregivers, physicians, and ethicists (among others) must have a voice in this continuing discussion.

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The objective of this study was to determine the relationship between the presence of extrapyramidal signs and the severity of cognitive and functional impairment in patients with Alzheimer's disease (AD). Eleven university medical centers in the United States and France participated in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) study of extrapyramidal signs in AD. Forty-seven patients with probable AD who had extrapyramidal signs were matched by sex, race, education, and age with 132 probable AD patients without extrapyramidal signs. The main outcome measures were the Clinical Dementia Rating, Blessed Dementia Scale, and the CERAD Neuropsychology Battery (verbal fluency, naming, Mini-Mental State Examination, word list learning, word list recall, savings ratio, word list recognition, and constructional praxis). AD patients with extrapyramidal signs performed more poorly than AD patients without parkinsonism on various neuropsychological tests, even after controlling for the Clinical Dementia Rating and reported duration of cognitive impairment. The severity of the extrapyramidal manifestations was related to the degree of cognitive and functional impairment. Muscular rigidity and bradykinesia were the most frequent extrapyramidal signs associated with AD. Patients with AD associated with extrapyramidal signs have greater cognitive and functional impairment than AD patients without clinical evidence of parkinsonism.