Jenny Brook

Relationship between hippocampal atrophy and neuropathology markers: a 7T MRI validation study of the EADC-ADNI Harmonized Hippocampal Segmentation Protocol

The pathologic validation of European Alzheimers Disease Consortium Alzheimer’s Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP).

Risk factors for behavioral abnormalities in mild cognitive impairment and mild Alzheimer's disease

Background: Behavioral symptoms are common in both mild cognitive impairment (MCI) and Alzheimers disease (AD). Methods: We analyzed the Neuropsychiatric Inventory Questionnaire data of 3,456 MCI and 2,641 mild AD National Alzheimers Coordinating Center database participants. Using factor analysis and logistic regression we estimated the effects of age, sex, race, education, Mini-Mental State Examination, functional impairment, marital status and family history on the presence of behavioral symptoms. We also compared the observed prevalence of behavioral symptoms between amnestic and nonamnestic MCI. Results: Four factors were identified: affective behaviors (depression, apathy and anxiety); distress/tension behaviors (irritability and agitation); impulse control behaviors (disinhibition, elation and aberrant motor behavior), and psychotic behaviors (delusions and hallucinations). Male gender was significantly associated with all factors. Younger age was associated with a higher prevalence of distress/tension, impulse control and psychotic behaviors. Being married was protective against psychotic behaviors. Lower education was associated with the presence of distress/tension behaviors. Caucasians showed a higher prevalence of affective behaviors. Functional impairment was strongly associated with all behavioral abnormalities. Amnestic MCI patients had more elation and agitation relative to nonamnestic MCI patients. Conclusions: Younger age, male gender and greater functional impairment were associated with higher overall presence of behavioral abnormalities in MCI and mild AD. Marital status, lower education and race had an effect on selected behaviors.

Tobacco Cessation Practices and Attitudes Among Nurses in the Czech Republic.

Background: Tobacco is the leading cause of cancer in the Czech Republic. More than one-third of the population older than 15 years smokes, including many nurses. Most smokers want to quit, but the extent of nurses’ involvement in tobacco cessation is unknown. Objective: The purposes of this study are to describe the frequency of nurses’ interventions in helping smokers quit, examine their attitudes and skills, and explore the relationship of nurses’ smoking status to level of intervention. Methods: A convenience sample of nurses in the Czech Republic completed a survey about their frequency of interventions according to the 5As for tobacco dependence treatment (ie, ask, advise, assess, assist, arrange), their attitudes and perceived skills, and their smoking status (never, former, current). Results: A total of 157 nurses completed the survey; 26% “always” or “usually” assisted patients with smoking cessation. Few (22%) reported that nurses could play an important role in helping patients quit, and 65% rated their ability to help smokers quit as “fair/poor.” Nurse who smoked (30%) were less likely to consistently assess smoking status or arrange for follow-up support. Conclusion: Few nurses in the Czech Republic consistently provide smoking cessation support to patients, have the skills to do so, or view this role as an important part of their role. Implications for Practice: To reduce tobacco-related cancers in the Czech Republic, capacity-building efforts are needed to enhance nurses’ skills and confidence in providing smoking cessation interventions. Support is also need to help nurses who smoke quit.

Impact of Online Education on Nurses’ Delivery of Smoking Cessation Interventions With Implications for Evidence‐Based Practice

BACKGROUND Tobacco use is the leading cause of preventable disease and death in Europe and worldwide. Nurses, if properly educated, can contribute to decreasing the burden of tobacco use in the region by helping smokers quit smoking. AIMS To assess: (a) the feasibility of an online program to educate nurses in Czech Republic and Poland on evidence-based smoking cessation interventions for patients and (b) self-reported changes in practices related to consistently (usually or always) providing smoking cessation interventions to smokers, before and 3 months after participation in the program. METHODS A prospective single-group pre-post design. RESULTS A total of 280 nurses from Czech Republic and 156 from Poland completed baseline and follow-up surveys. At 3 months, nurses were significantly more likely to provide smoking cessation interventions to patients who smoke and refer patients for cessation services (p < .01). Nurses significantly improved their views about the importance of nursing involvement in tobacco control. IMPLICATIONS FOR PRACTICE Education about tobacco control can make a difference in clinical practice, but ongoing support is needed to maintain these changes. Health system changes can also facilitate the expectation that delivering evidence-based smoking cessation interventions should be routine nursing care. LINKING EVIDENCE TO ACTION Educating nurses on cessation interventions and tobacco control is pivotal to decrease tobacco-related disparities, disease, and death. Online methods provide an accessible way to reach a large number of nurses.

Estriol-mediated neuroprotection in multiple sclerosis localized by voxel-based morphometry

Progressive gray matter (GM) atrophy is a hallmark of multiple sclerosis (MS). Cognitive impairment has been observed in 40%–70% of MS patients and has been linked to GM atrophy. In a phase 2 trial of estriol treatment in women with relapsing–remitting MS (RRMS), higher estriol levels correlated with greater improvement on the paced auditory serial addition test (PASAT) and imaging revealed sparing of localized GM in estriol‐treated compared to placebo‐treated patients. To better understand the significance of this GM sparing, the current study explored the relationships between the GM sparing and traditional MRI measures and clinical outcomes.

Attitudes toward clinical trials across the Alzheimer’s disease spectrum

BackgroundResearch has revealed that manifest Alzheimer’s disease (AD) dementia is preceded by preclinical and prodromal phases during which pathology is accumulating but function remains intact. This understanding and concern that disease-modifying interventions initiated at the dementia stage may come too late in the neurodegenerative process to be successful has led to a paradigm shift in AD clinical trials. AD trials now enroll patients with mild cognitive impairment (MCI) and persons with no cognitive symptoms. Trial designs are similar to those enrolling dementia participants. We set out to test the hypothesis that attitudes towards trial design features differ among different potential AD trial populations.MethodsWe sent a survey composed of 37 items assessing specific trial elements to 246 cognitively normal, MCI, and AD dementia participants at the University of California Los Angeles (UCLA) Alzheimer’s Disease Research Center (ADRC), from whom we received 91 responses (37 cognitively normal, 32 MCI, and 22 dementia). To quantify willingness to enroll, we created three composite scenarios by summing responses and fitting proportional odds models with a binary outcome variable for whether patients were highly willing to participate in low-, moderate-, or high-risk and burden trials.ResultsMCI participants less frequently correctly self-identified their diagnoses than those with dementia or normal cognition. Compared to dementia patients, the odds of participating in a low-risk, low-burden trial were 12% lower for MCI patients (odds ratio (OR) = 0.88, 95% confidence interval (CI) 0.23–3.29) and 70% lower (OR = 0.30, 95% CI 0.08–1.09) for cognitively normal participants. With increasing risk and burden, willingness to enroll decreased and the gap in relative willingness between diagnostic groups increased. In the medium-risk, medium-burden scenario, the estimated OR was 0.64 (95% CI 0.17–2.40) for MCI and 0.21 for the cognitively normal (95% CI 0.06–0.77). In the high-risk, high-burden scenario, the estimated OR indicated reduced willingness for MCI (OR = 0.27, 95% CI 0.06–1.15) and cognitively normal respondents (OR = 0.12, 95% CI 0.03–0.54).ConclusionsThese results suggest that AD trials enrolling predementia populations, especially those requiring frequent visits and implementing biomarker testing procedures, may encounter challenges to enrollment.

Participant–Informant Relationships Affect Quality of Life Ratings in Incipient and Clinical Alzheimer Disease

OBJECTIVE Clinical trials in incipient and clinical Alzheimer disease (AD) often include informant-reported outcomes. Whereas informant reports in AD dementia may be modulated by the nature of participant-informant relationships, whether informant type affects reporting at earlier disease stages is less certain. We sought to determine the effects of participant-informant relationships on informant assessments of quality of life (QOL), functional abilities, and behavioral symptoms in individuals with normal cognition (NC), mild cognitive impairment (MCI), and mild-to-moderate AD dementia. DESIGN Cross-sectional. SETTING Easton Center for Alzheimer Disease Research at the University of California, Los Angeles. PARTICIPANTS A total of 399 individuals who met criteria for NC (N = 100), MCI [amnestic (N = 125) and nonamnestic (N = 61)], and AD (N = 113). Participants were subdivided into groups based on informant-participant relationships (spouse versus other). MEASUREMENTS We examined informant effects on the Quality of Life-Alzheimers Disease (QOL-AD) scale, the Functional Activities Questionnaire (FAQ), and the Neuropsychiatric Inventory (NPI). RESULTS After adjustments for demographic and cognitive factors, spouse informants reported higher participant QOL in the amnestic MCI and AD groups than did other informants. No informant effects were seen on QOL-AD ratings in the nonamnestic MCI or NC groups or on the FAQ or NPI in the MCI and AD groups. CONCLUSIONS Participant-informant relationships may modulate informant responses on subjective measures such as the QOL-AD in both incipient and clinical AD. Clinical trials that use informant measures may need to address these effects.

Elevated baseline power Doppler discriminates an RA subgroup highly responsive to therapy

SIR, Recent systematic literature reviews and expert panel recommendations by the ACR and the EULAR support the use of musculoskeletal US (MSUS) in monitoring RA disease activity [1, 2]. MSUS is inexpensive and enables multiple point-of-care assessments. Power Doppler US (PDUS) score measures synovitis and may be useful in assessing response to therapy, where studies have reported suppression of PDUS signal after administration of RA treatment [3, 4]. This study evaluates the predictive value of baseline PDUS measures on response to drug by the DAS28 and clinical disease activity index (CDAI) in RA. Few studies have evaluated the association between MSUS and co-morbidities, and we investigate this concept as well. This report describes the results of a pilot 12 month open-label s.c. abatacept study of 25 RA patients naive to biologics. The study was approved by the University of California, Los Angeles institutional review board, registered on clinicaltrials.gov (NCT01299961), and all patients signed an informed consent form. Inclusion criteria were as follows: ACR 1987 RA diagnostic criteria; age 518 years; stable DMARDs; no prior exposure to biologics; DAS28/ESR >3.2; prednisone 410 mg; and total PDUS 51 for at least two MCP joints. Patients completed detailed questionnaires regarding their demographics, function and comorbidities. MSUS assessment of PDUS was performed at baseline, 3 weeks, 3, 6 and 12 months. A GE Logic E9 machine with ML6-15 probe (GE Healthcare) was used. Seven joints were scanned by MSUS of the most affected side (wrist, MCP joint 2/3, PIP joint 2/3 and MTP joint 2/5) according to Backhaus et al. [5]. PDUS was scored semiquantitatively according to published consensus definitions [6]. The clinical assessor was blinded to the US data and vice versa. In addition, when scoring images, the ultrasonographer was blinded to the sequence of the visits and patient. All 25 patients enrolled in the study completed at least 3 months of therapy with s.c. abatacept. Nineteen of the 25 patients completed the 12 month visit. Six patients dropped out for the following reasons: lack of efficacy (two patients); adverse events [three patients (recurrent oral ulcers, erythema nodosum, chronic obstructive pulmonary disease exacerbation), no serious adverse events]; and lost to follow-up (one patient). Patients were separated into two groups based on median baseline PDUS of complete cases: patients with baseline PDUS <5 and patients with baseline PDUS 55 (Table 1). Interestingly, the changes between baseline and 12 months for DAS28/ESR, CDAI and the HAQ disability index (HAQ-DI) for the PDUS 55 group were significantly greater than seen in the PDUS <5 group, where patients in the PDUS 55 group experienced more than twice the magnitude of improvement (DAS28 change of 1.1 vs change of 2.7, CDAI change of 12.8 vs change of 28.0, and HAQ-DI change of 0.3 vs change of 0.8). Baseline PDUS was significantly correlated with change in DAS28/ESR at 12 months (DAS28/ESR = 0.65, P< 0.01). We also performed a multivariate linear regression for change in DAS28/ESR as the outcome, with baseline PDUS and baseline DAS28/ESR as the predictors. Baseline PDUS was almost significantly associated with change in DAS28/ESR (P = 0.06), after accounting for baseline DAS28/ESR (P = 0.52). The number of comorbidities was significantly higher in those with PDUS< 5 (P = 0.02). Lastly, we found that lower baseline

PATHOLOGIC VALIDATION OF THE EADC-ADNI HARMONIZED HIPPOCAMPAL PROTOCOL

monoclonal antibody, in patients with prodromal or mild Alzheimer’s disease (AD). Retrospective analyses of both bapineuzumab and solanezumab data have shown substantially higher percentages of negative amyloid PET findings in APOE ε4 non-carriers than in APOE ε4 carriers in the mild and moderate AD sub-study populations. We report our amyloid PET screening results by APOE ε4 status in the prodromal and mild AD study populations. Methods: During screening, patients fulfilling clinical criteria for either prodromal or mild AD underwent florbetapir PET scanning and APOE genotyping. Florbetapir PET scans were visually evaluated for amyloid plaque burden. Results: Data from the first 250 patients were included in this analysis. Similar to the bapineuzumab and solanezumab results, we have observed a substantially higher percentage of negative amyloid PET findings in APOE ε4 non-carriers than in APOE ε4 carriers (highlighted in bold in Table 1). However, the overall incidence of negative amyloid scans observed in 221AD103 is substantially higher than that reported in the two Phase III studies, likely attributable to the earlier stage of AD patients being recruited in this study (prodromal/mild, mean MMSE w 25 vs. mild/moderate AD, mean MMSE w21 in the Phase III studies). This finding is also consistent with the solanezumab results in that the percentage of negative amyloid PET findings was higher in mild (27%) than in moderate (13%) AD groups. Conclusions: These results suggest that: (1) selecting subjects having AD pathology based on clinical criteria remains a challenge; (2) enrichment by using amyloid PET imaging is effective and feasible; (3) enrichment by assessing amyloid plaque burden is critically important to clinical studies in early stages of AD because of a higher incidence of negative amyloid findings; and (4) APOE genotyping may potentially improve the economy of enrichment by amyloid PET, via lowering the likelihood of negative amyloid findings.