Kristin Harkins

Development of a process to disclose amyloid imaging results to cognitively normal older adult research participants

IntroductionThe objective of this study was to develop a process to maximize the safety and effectiveness of disclosing Positron Emission Tomography (PET) amyloid imaging results to cognitively normal older adults participating in Alzheimer’s disease secondary prevention studies such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Study.MethodsUsing a modified Delphi Method to develop consensus on best practices, we gathered and analyzed data over three rounds from experts in two relevant fields: informed consent for genetic testing or human amyloid imaging.ResultsExperts reached consensus on (1) text for a brochure that describes amyloid imaging to a person who is considering whether to undergo such imaging in the context of a clinical trial, and (2) a process for amyloid PET result disclosure within such trials. Recommendations included: During consent, potential participants should complete an educational session, where they receive verbal and written information covering what is known and unknown about amyloid imaging, including possible results and their meaning, implications of results for risk of future cognitive decline, and information about Alzheimer’s and risk factors. Participants should be screened for anxiety and depression to determine suitability to receive amyloid imaging information. The person conducting the sessions should check comprehension and be skilled in communication and recognizing distress. Imaging should occur on a separate day from consent, and disclosure on a separate day from imaging. Disclosure should occur in person, with time for questions. At disclosure, investigators should assess mood and willingness to receive results, and provide a written results report. Telephone follow-up within a few days should assess the impact of disclosure, and periodic scheduled assessments of depression and anxiety, with additional monitoring and follow-up for participants showing distress, should be performed.ConclusionsWe developed a document for use with potential study participants to describe the process of amyloid imaging and the implications of amyloid imaging results; and a disclosure process with attention to ongoing monitoring of both mood and safety to receive this information. This document and process will be used in the A4 Study and can be adapted for other research settings.

Using AD biomarker research results for clinical care A survey of ADNI investigators

Objective: To inform whether the Alzheimers Disease Neuroimaging Initiative (ADNI) should change its policy of not returning research results to ADNI participants, we surveyed investigators and research staff about disclosing ADNI biomarker information to research participants, with particular emphasis on amyloid imaging results. Methods: In April 2012, just before Food and Drug Administration approval of the amyloid-binding radiotracer, florbetapir, all ADNI investigators and personnel were recruited to complete an anonymous online survey that contained fixed choice and free-text questions. Results: Although ADNI participants often requested amyloid imaging results (the proportions of investigators who reported requests from more than half of their participants with normal cognition or mild cognitive impairment were 20% and 22%, respectively), across all diagnostic groups, the majority of ADNI investigators (approximately 90%) did not return amyloid imaging results to ADNI participants. However, the majority of investigators reported that, if the Food and Drug Administration approved florbetapir, they would support the return of amyloid imaging results to participants with mild cognitive impairment and normal cognition, but they emphasized the need for guidance on how to provide these results to participants and for research to assess the value of returning results as well as how returning results will affect study validity and participant well-being. Conclusions: A majority of ADNI investigators support returning amyloid imaging results to ADNI participants. The findings that they want guidance on how to do this and research on the impact of disclosure suggest how to develop and monitor a disclosure process.

A Mixed-Methods Randomized Controlled Trial of Financial Incentives and Peer Networks to Promote Walking Among Older Adults

Background. Financial incentives and peer networks could be delivered through eHealth technologies to encourage older adults to walk more. Methods. We conducted a 24-week randomized trial in which 92 older adults with a computer and Internet access received a pedometer, daily walking goals, and weekly feedback on goal achievement. Participants were randomized to weekly feedback only (Comparison), entry into a lottery with potential to earn up to

A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease.

200 each week walking goals were met (Financial Incentive), linkage to four other participants through an online message board (Peer Network), or both interventions (Combined). Main outcomes were the proportion of days walking goals were met during the 16-week intervention and 8-week follow-up. We conducted a content analysis of messages posted by Peer Network and Combined arm participants. Results. During the 16-week intervention, there were no differences in the proportion of days walking goals were met in the Financial Incentive (39.7%; p = .78), Peer Network (24.9%; p = .08), and Combined (36.0%; p = .77) arms compared with the Comparison arm (36.0%). During 8 weeks of follow-up, the proportion of days walking goals were met was lower in the Peer Network arm (18.7%; p = .025) but not in the Financial Incentive (29.3%; p = .50) or Combined (24.8%; p = .37) arms, relative to the Comparison arm (34.5%). Messages posted by participants focused on barriers to walking and provision of social support. Conclusions. Financial incentives and peer networks delivered through eHealth technologies did not result in older adults walking more.

Comprehension of an Elevated Amyloid Positron Emission Tomography Biomarker Result by Cognitively Normal Older Adults

Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimers disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD.

Identifiable Characteristics and Potentially Malleable Beliefs Predict Stigmatizing Attributions Toward Persons With Alzheimer’s Disease Dementia: Results of a Survey of the U.S. General Public

Importance The goal of Alzheimer disease (AD) prevention together with advances in understanding the pathophysiology of AD have led to clinical trials testing drugs in cognitively unimpaired persons who show evidence of AD biomarkers. Data are needed to inform the processes of describing AD biomarkers to cognitively normal adults and assessing their understanding of this knowledge. Objective To determine the comprehension of an elevated amyloid positron emission tomographic (PET) biomarker result by cognitively unimpaired adults. Design, Setting, and Participants The Study of Knowledge and Reactions to Amyloid Testing, a substudy of an AD prevention trial, involved 2 semistructured telephone interviews with 80 participants recruited from 9 study sites: 50 received elevated and 30 received not elevated amyloid PET scan results. Interviews were conducted 4 to 12 weeks after result disclosure and again 1 year later. Data presented here were collected from November 5, 2014, through December 10, 2015. The 50 participants included in this study were cognitively normal, aged 65 to 85 years, evenly distributed by gender, and had elevated amyloid PET results. Subsequent reports will examine persons with “not elevated” results and compare the influence of the different results. Main Outcomes and Measures Participant comprehension of an elevated amyloid result was assessed by analyzing their responses to the following questions: “What was the result of your amyloid PET scan?” (followed by “Can you tell me in your own words what that means?” or “How would you explain it to a friend?”), “Was it the result you expected?” and “Did the result teach you anything or clarify anything for you?” Results Of the 50 participants aged 65 to 85 years, 49 (98%) were white, 40 (80%) reported a family history of AD, and 30 (60%) had a postgraduate educational level. Most participants (31 [62%]) understood that elevated amyloid conferred an increased but uncertain risk of developing AD. Some desired understanding of the term elevated other than its being a categorical result enabling trial entry eligibility; they wanted information regarding how elevated their amyloid was, how close to the study threshold they were, or percentages, numbers, or a scale to help them make sense of the result. Conclusions and Relevance Including an explanation of how and why a dimensional biomarker is converted to a categorical classification would enhance future AD biomarker clinical trials and educational materials.

Awareness of Mild Cognitive Impairment and Mild Alzheimer’s Disease Dementia Diagnoses Associated With Lower Self-Ratings of Quality of Life in Older Adults

ABSTRACT The general public’s views can influence whether people with Alzheimer’s disease (AD) experience stigma. The purpose of this study was to understand what characteristics in the general public are associated with stigmatizing attributions. A random sample of adults from the general population read a vignette about a man with mild Alzheimer’s disease dementia and completed a modified Family Stigma in Alzheimer’s Disease Scale (FS-ADS). Multivariable ordered logistic regressions were used to examine relationships between personal characteristics and FS-ADS ratings. Older respondents expected that persons with AD would receive less support (OR = 0.82, p = .001), have social interactions limited by others (OR = 1.13, p = .04), and face institutional discrimination (OR = 1.13, p = .04). Females reported stronger feelings of pity (OR = 1.57, p = .03) and weaker reactions to negative aesthetic features (OR = 0.67, p = .05). Those who believed strongly that AD was a mental illness rated symptoms more severely (OR = 1.78, p = .007). Identifiable characteristics and beliefs in the general public are related to stigmatizing attributions toward AD. To reduce AD stigma, public health messaging campaigns can tailor information to subpopulations, recognizable by their age, gender, and beliefs.

AWARENESS OF MILD COGNITIVE IMPAIRMENT AND MILD ALZHEIMER’S DISEASE DEMENTIA DIAGNOSES IS ASSOCIATED WITH DECREASED SELF-RATINGS OF QUALITY OF LIFE IN OLDER ADULTS

Objective This study examined how awareness of diagnostic label impacted self-reported quality of life (QOL) in persons with varying degrees of cognitive impairment. Method Older adults (n = 259) with normal cognition, Mild Cognitive Impairment (MCI), or mild Alzheimers disease dementia (AD) completed tests of cognition and self-report questionnaires that assessed diagnosis awareness and multiple domains of QOL: cognitive problems, activities of daily living, physical functioning, mental wellbeing, and perceptions of ones daily life. We compared measures of QOL by cognitive performance, diagnosis awareness, and diagnostic group. Results Persons with MCI or AD who were aware of their diagnosis reported lower average satisfaction with daily life (QOL-AD), basic functioning (BADL Scale), and physical wellbeing (SF-12 PCS), and more difficulties in daily life (DEM-QOL) than those who were unaware (all p ≤ .007). Controlling for gender, those expecting their condition to worsen over time reported greater depression (GDS), higher stress (PSS), lower quality of daily life (QOL-AD, DEM-QOL), and more cognitive difficulties (CDS) compared to others (all p < .05). Discussion Persons aware of their diagnostic label-either MCI or AD-and its prognosis report lower QOL than those unaware of these facts about themselves. These relationships are independent of the severity of cognitive impairment.

WHICH SELF-REPORTED COGNITIVE DIFFICULTIES DIFFERENTIATE COGNITIVELY NORMAL OLDER ADULTS FROM THOSE WITH MCI?

Background: Decision-making about driving and transitioning to non-driving is a challenging and complex issue faced by all drivers diagnosed with dementia and their families. To address the gap in evidence-based interventions that support individuals in this process we developed the Driving Cessation Decision-Making and Coping Framework and Toolkit (DCDT). Our objective is to further develop and refine the DCDT (content, design and mode of delivery), based on the perspectives of key informants, to facilitate its effective implementation in settings that support older adults with dementia. This study reports on the development of the DCDT and the results of the initial phase of a multi-phase qualitative research project aimed to evaluate the DCDT’s design and implementation process. Methods: A focus group (n1⁄48) comprised of key stakeholders (family members, a former diver with dementia and a social worker) was conducted at an Alzheimer Society organization, following a presentation of the DCDT. The interaction element in focus groups allows for multiple point of views, and considerations of various understandings and collective ideas about a topic. Participants were asked to report on their impressions of the DCDT including its strengths and weaknesses. The discussion was audio-recorded and transcribed verbatim for analysis. Data analysis techniques included thematic coding and inductive analysis. Results: Interrelated themes derived from participants’ accounts focused on the delivery of the toolkit including its mode of delivery, structure and accessibility. Across these areas, themes of consideration for designing and disseminating the toolkit are: integrating a systems-oriented approach (e.g. targeting GPs and transportation organizations); accounting for varied contexts of users (e.g. adapting language to address specific needs, stages of driving cessation and age cohorts) and attending to how users experience the toolkit (e.g. ensure it promotes a sense of autonomy and is non-stigmatizing). Conclusions: Obtaining the perspectives of individuals with dementia, their family caregivers and healthcare/ service providers is critical to designing an intervention toolkit that can effectively assist with decisions about driving and providing support with the transition to non-driving. This feedback is essential throughout the design process to ensure that on-going considerations raised by these key stakeholders continue to be addressed.

Development of a genetic education and genetic risk disclosure protocol for individuals with mild cognitive impairment

and 3D T1-weighted MR images were obtained from ADNI-GO/-2 study subjects diagnosed with mild cognitive impairment (MCI). PET volumes were registered to a customized MRI template in MNI stereotaxic space, and standardized uptake value ratio (SUVR) images were generated using Biospective’s fully-automated PIANO TM image processing software. The amyloid burden for each subject was determined from a composite region-of-interest (ROI) on [18F]florbetapir images, and subjects were categorized into Amyloid-Low (Ab L) and Amyloid-High (Ab H) groups. We generated a set of hierarchical likelihood ratio tests to assess betweengroups differences in metabolic connectivity patterns arising from (1) alterations in seed-based correlations and (2) alterations in seed-based covariances and variances with stable seed-based correlations. Results: We observed statistically significant differences in metabolic correlations between the Ab L and Ab H groups for multiple cortical seeds regions, including the angular gyrus and the inferior temporal gyrus. The seed-based covariance analysis identified connectivity patterns in particular brain regions (e.g. precuneus) that were not detected by classical seed-based correlation analysis. Conclusions: We have introduced a new, multivariate metabolic connectivity analysis technique to examine disruptions of the cortical correlation architecture as a function of b-amyloid burden. The novel approach employed in this study may be generalized to other connectivity measures, such as functional connectivity derived from BOLD fMRI, and may provide unique insights into disease-related alterations of the connectome. with MOCA with GDS OR P