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Disclosure of personal disease‐related information to asymptomatic adults has been debated over the last century in medicine and research. Recently, Alzheimer's disease (AD) has been conceptualized as a continuum that begins with a “preclinical” stage in which biomarkers are present in the absence of cognitive impairment. Studies have begun assessing the safety, psychological, and behavioral effects of disclosing both AD‐related genetic and biomarker information to cognitively unimpaired older adults. Yet, debate continues over the appropriate circumstances and methods for returning such information. This article outlines concerns with and rationale for AD biomarker disclosure and summarizes findings from prior studies. Overall, this article aims to describe and respond to key questions concerning disclosure of amyloid positron emission tomography scan results to asymptomatic adults in a research setting. Moving forward, such conditions are important to consider as interventions target the preclinical phase of AD and normalize disclosing biomarker information to cognitively unimpaired persons.

Introduction This study applies a novel algorithm to longitudinal amyloid positron emission tomography (PET) imaging to identify age‐heterogeneous amyloid trajectory groups, estimate the age and duration (chronicity) of amyloid positivity, and investigate chronicity in relation to cognitive decline and tau burden. Methods Cognitively unimpaired participants (n = 257) underwent one to four amyloid PET scans (Pittsburgh Compound B, PiB). Group‐based trajectory modeling was applied to participants with longitudinal scans (n = 171) to identify and model amyloid trajectory groups, which were combined with Bayes theorem to estimate age and chronicity of amyloid positivity. Relationships between chronicity, cognition, clinical progression, and tau PET (MK‐6240) were investigated using regression models. Results Chronicity explained more heterogeneity in amyloid burden than age and binary amyloid status. Chronicity was associated with faster cognitive decline, increased risk of abnormal cognition, and higher entorhinal tau. Discussion Amyloid chronicity provides unique information about cognitive decline and neurofibrillary tangle development and may be useful to investigate preclinical Alzheimer's disease.

Background Insulin resistance (IR) and type 2 diabetes have been found to increase the risk for Alzheimer’s clinical syndrome in epidemiologic studies but have not been associated with tau tangles in neuropathological research and have been inconsistently associated with cerebrospinal fluid P-tau181. IR and type 2 diabetes are well-recognized vascular risk factors. Some studies suggest that cardiovascular risk may act synergistically with cortical amyloid to increase tau measured using tau PET. Utilizing data from largely nondemented middle-aged and older adult cohorts enriched for AD risk, we investigated the association of IR and diabetes to tau PET and whether amyloid moderated those relationships. Methods Participants were enrolled in either the Wisconsin Registry for Alzheimer’s Prevention (WRAP) or Wisconsin Alzheimer’s Disease Research Center (WI-ADRC) Clinical Core. Two partially overlapping samples were studied: a sample characterized using HOMA-IR ( n =280 WRAP participants) and a sample characterized on diabetic status ( n =285 WRAP and n =109 WI-ADRC). IR was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). Tau PET employing the radioligand 18 F-MK-6240 was used to detect AD-specific aggregated tau. Linear regression tested the relationship of IR and diabetic status to tau PET standardized uptake value ratio (SUVR) within the entorhinal cortex and whether relationships were moderated by amyloid assessed by amyloid PET distribution volume ratio (DVR) and amyloid PET positivity status. Results Neither HOMA-IR nor diabetic status was significantly associated with tau PET SUVR. The relationship between IR and tau PET SUVR was not moderated by amyloid PET DVR or positivity status. The association between diabetic status and tau PET SUVR was not significantly moderated by amyloid PET DVR but was significantly moderated by amyloid PET positivity status. Among the amyloid PET-positive participants, the estimated marginal tau PET SUVR mean was higher in the diabetic ( n =6) relative to the nondiabetic group ( n =88). Conclusion Findings indicate that IR may not be related to tau in generally healthy middle-aged and older adults who are in the early stages of the AD clinicopathologic continuum but suggest the need for additional research to investigate whether a synergistic relationship between type 2 diabetes and amyloid is associated with increased tau levels.

Increased availability of Alzheimer's disease (AD) biomarker tests provides older adults with opportunities to seek out and learn results. We evaluated the feasibility of virtually returning AD biomarker results. Trained study clinicians disclosed amyloid positron emission tomography (PET) results and provided dementia risk-reduction counseling via televideo to cognitively unimpaired participants already enrolled in AD research ( = 99; mean age ± SD: 72.0 ± 4.8; 67% women; 95% White; 28% amyloid elevated). Our study demonstrated acceptable levels of retention (93%), compliance (98%), adherence (98%), clinician competence (97%), education comprehension (quiz scores 14/15), and virtual visit functionality (rating 9.4/10). Depression, anxiety, and suicidality remained low and did not differ by amyloid result. Virtual return of amyloid PET results to cognitively unimpaired research participants is feasible and does not result in increased psychological symptoms. Technological barriers for some participants highlight the need for flexibility. These findings support the use of televideo in AD biomarker disclosure, although our study sample and design have important limitations for generalizability.

Introduction We developed the Alzheimer’s Biomarker Survey to assess willingness to enroll in biomarker studies that disclose results and anticipated reactions to an elevated biomarker result. Methods Participants included cognitively unimpaired adults enrolled in longitudinal AD studies ( n  = 334, mean age = 64.8 ± 7.7, 44% non-Hispanic Black or African American). Exploratory and confirmatory factor analyses determined the latent structure comprising anticipated reactions to learning AD biomarker results. Measurement invariance was tested across racial groups. Results Two models comprising behavior change and psychological impact fit well for the total sample and the two racial groups. The 2-factor behavior change model assessed constructs of planning and dementia risk-reduction. The 3-factor psychological impact model assessed constructs of distress, cognitive symptoms, and stigma. Both models exhibited measurement invariance across racial groups. Discussion The 28-item Anticipated Reactions to AD Biomarker Disclosure scale is a reliable and valid measure of anticipated reactions when communicating AD biomarker results to research participants.

Introduction As the population ages, Alzheimer’s disease and related dementias (ADRD) are becoming increasingly common in patients presenting to the emergency department (ED). This study compares the frequency of ED use among a cohort of individuals with well-defined cognitive performance (cognitively intact, mild cognitive impairment (MCI), and ADRD). Methods We performed a retrospective cohort study of English-speaking, community-dwelling individuals evaluated at four health system-based multidisciplinary memory clinics from 2014–2016. We obtained demographic and clinical data, including neuropsychological testing results, through chart review and linkage to electronic health record data. We characterized the frequency and quantity of ED use within one year (6 months before and after) of cognitive evaluation and compared ED use between the three groups using bivariate and multivariate approaches. Results Of the 779 eligible patients, 89 were diagnosed as cognitively intact, 372 as MCI, and 318 as ADRD. The proportion of subjects with any annual ED use did not increase significantly with greater cognitive impairment: cognitively intact (16.9%), MCI (26.1%), and ADRD (28.9%) ( p  = 0.072). Average number of ED visits increased similarly: cognitively intact (0.27, SD 0.72), MCI (0.41, SD 0.91), and ADRD (0.55, SD 1.25) ( p  = 0.059). Multivariate logistic regression results showed that patients with MCI (odds ratio (OR) 1.62; CI = 0.87–3.00) and ADRD (OR 1.84; CI = 0.98–3.46) did not significantly differ from cognitively intact adults in any ED use. Multivariate negative binomial regression found patients with MCI (incidence rate ratio (IRR) 1.38; CI = 0.79–2.41) and ADRD (IRR 1.76, CI = 1.00–3.10) had elevated but non-significant risk of an ED visit compared to cognitively intact individuals. Conclusion Though there was no significant difference in ED use in this small sample from one health system, our estimates are comparable to other published work. Results suggested a trend towards higher utilization among adults with MCI or ADRD compared to those who were cognitively intact. We must confirm our findings in other settings to better understand how to optimize systems of acute illness care for individuals with MCI and ADRD.

Primary care professionals play a critical role in the care of their patients. In clinical practice, early detection and diagnosis of Mild Cognitive Impairment, Alzheimer's disease and related dementia are often missed or delayed. Disclosure of diagnosis is not timely or not revealed. Though the methods that could improve early detection and diagnosis have remained the same over the decades with little change, they provide opportunities for early intervention, treatment and improvement in patient care. Emerging research suggests that though the disease process begins years prior to the clinical diagnosis, the healthcare system and health care professionals remain distant and reluctant to provide the service of annual cognitive assessment, which has been recommended by the Medicare program for older adults aged 65 years and older. Findings support that Alzheimer's disease and related cognitive impairments have gone under detected, underdiagnosed and undertreated. This article seeks to provide valuable and equitable information in the form of a clinician's guide for removing the barriers to early detection and diagnosis of cognitive impairments and offers an unprecedented opportunity to improve the clinical outcomes and care of older adults with various levels of cognitive decline, including mild cognitive impairment, Alzheimer's disease, and related dementias. This article provides information on understanding and addressing the challenges faced by health care professionals, including primary care clinicians; removing the barriers to cognitive assessments; educating this professional group on the importance of brain health, early detection, and diagnosis for their older adult patients; and providing these professionals with the ability to transfer their knowledge into more defined care planning. Until cognitive screening has been fully accepted and implemented for the optimal the care of older adults, health-related efforts should include the promotion and education of brain health, early detection, and diagnosis in the education of health care providers.

Vascular dysfunction may occur prior to declines in cognitive function and accumulation of neuropathology. White matter hyperintensities (WMH) develop due to cerebral ischemia and elevated blood pressure in midlife. The purpose of this study was to evaluate associations between cardiovascular and cerebrovascular responses to sympathoexcitatory stimuli and WMH burden in cognitively unimpaired middle-aged and older adults. Sixty-eight adults (age=63±4y, men=20, women=48) participated in this study. Participants completed isometric handgrip exercise (IHG) exercise at 40% of maximal voluntary contraction until fatigue followed by a 90s period of post-exercise ischemia. Heart rate (HR), mean arterial pressure (MAP), middle cerebral artery blood velocity (MCAv), and end-tidal CO2 were continuously measured throughout the protocol. Cerebrovascular resistance index (CVRi) was calculated as MAP/MCAv. WMH lesion volume and intracranial volume (ICV) were measured using a FLAIR and T1 scan on a 3T MRI scanner, respectively. WMH fraction was calculated as (WMH lesion volume/ICV)*100 and cubic root transformed. Multiple linear regressions were used to determine the association between the cardiovascular and cerebrovascular responses to IHG exercise and post-exercise ischemia and WMH fraction. Multiple linear regression models were adjusted for age, sex, apolipoprotein ε4 status, and total work performed during IHG exercise. During IHG exercise, there were significant increases from baseline in HR (25±12%), MAP (27±11%), MCAv (5±10%), and CVRi (22±17%; P<0.001 for all). During post-exercise ischemia, HR (8±7%), MAP (22±9%), and CVRi (23±16%) remained elevated (P<0.001) while MCAv (0±10%) was not different compared to baseline. There was an inverse association between the percent change in HR (r=-0.42, P=0.002), MAP (r=-0.41, P=0.002), and CVRi (r=-0.31, P=0.045), but not MCAv (r=0.19, P=0.971) in response to IHG exercise and WMH fraction. There were no associations between responses to post-exercise ischemia and WMH fraction. Lower sympathoexcitatory responses to IHG exercise are associated with greater WMH burden in middle-aged to older adults. These findings suggest that individuals who demonstrate smaller increases in HR, MAP, and CVRi in response to sympathoexcitatory stress have greater WMH burden.

Introduction Recruitment and retention pose a significant challenge to Alzheimer's disease (AD) research. Returning AD biomarker results to participants has been proposed as a means to improve recruitment and retention. We present findings related to participant satisfaction, utility, and impact on research attitudes from the amyloid positron emission tomography (PET) disclosure sub‐study within the Wisconsin Registry for Alzheimer's Prevention (WRAP). Methods Ninety‐nine cognitively unimpaired WRAP participants learned their amyloid PET results (mean age ± SD = 72.0 ± 4.8). Measures of reasons for wanting to learn results, study comprehension, result utility, visit satisfaction, research attitudes, and future study enrollment willingness were collected. Between‐group, chi‐squared analysis was conducted to determine differences by result type (elevated vs. not elevated amyloid PET result) in study comprehension, result utility, and visit satisfaction. Linear mixed‐effects modeling was used to evaluate changes in research attitudes and enrollment willingness as a function of time, amyloid result type (elevated/not elevated), and their interaction. Results The reasons most frequently endorsed for wanting to learn amyloid PET result was a “desire to contribute to research on Alzheimer's disease dementia” and “to inform preventative measures [one] might take (e.g., change diet, exercise, or other lifestyle changes).” Overall, participants reported understanding the results and found learning them useful. Satisfaction with the study visits was overwhelmingly high, with over 80% agreeing with visit usefulness and their satisfaction. Few differences were found between participants who learned an elevated and not elevated result. Over the course of the study, participants who learned an elevated amyloid PET result reported higher willingness to enroll in drug trials (beta: 0.12, p = 0.01) and lifestyle interventions (beta: 0.10, p = 0.02) compared to participants who learned a not elevated result. Discussion Formal incorporation of disclosure practices may encourage participant recruitment and retention within AD research. Highlights Participants wanted to learn their amyloid results to contribute to research. Satisfaction with disclosure and post‐disclosure visits was high overall. Returning AD biomarkers can increase willingness to participate in research.

In the asymptomatic \"preclinical\" phase of Alzheimer's disease (AD), abnormal biomarkers indicate risk for developing cognitive impairment. Biomarker information is increasingly being disclosed to participants in research settings, and biomarker testing and results disclosure will be implemented in clinical settings in the future. Biomarker disclosure has potential psychosocial benefits and harms, impacting affected individuals and their support person(s). Limited data are available about with whom research participants share their results, information that will be necessary to develop disclosure protocols and post-disclosure resources. Additionally, existing research has been conducted in largely White cohorts, limiting applicability to future clinical populations. We enrolled a diverse cohort of 329 adults (184 non-Hispanic White and 145 Black/African American individuals) who previously participated in AD research. After reviewing a vignette describing a hypothetical biomarker research study, participants indicated their anticipated willingness to share biomarker results with loved ones, and what reactions they anticipated from others. Using mixed-methods analysis, we identified responses related to willingness to share results. A majority (78.7%) were willing to share their results with support persons. Many (59.6%) felt it would not be difficult to share, and most (90.6%) believed their loved ones would be supportive. The most common reasons for sharing were to prepare for possible future AD (41.0% of respondents), while the most common reason for not sharing was to avoid worrying loved ones (4.8% of respondents). A total of 7.3% of respondents related reasons regarding being unsure about sharing. Participants' interest in sharing results supports integrating support persons into AD biomarker research, and may help maximize potential benefits for participants. Communicating with this \"dyad\" of research participant and support person(s) may improve involvement in research, and help prepare for implementation of clinical biomarker testing by clarifying communication preferences and the influence of support persons on psychosocial outcomes.