Amyloid burden and APOE modify sex differences in estimated meta‐temporal region tau onset age.

Background: Recent advances in Alzheimer’s disease (AD) temporal biomarker modeling have revealed considerable heterogeneity in age at amyloid onset, and recently we and others identified sex and APOE differences in tau onset age and subsequent dementia development. Here we assessed whether amyloid burden, APOE‐ε4 dose, and sex interact to predict estimated T+ onset age (ETOA).

Methods: Alzheimer’s Disease Neuroimaging Initiative participants (N=911, Table 1) underwent serial PET imaging to quantify global cortical amyloid ([18F]Florbetapir SUVR, [18F]Florbetaben SUVR) and meta‐temporal tau ([18F]Flortaucipir SUVR) burden.

Whole genome methylation sequencing in blood identifies extensive differential DNA methylation in mild cognitive impairment (MCI).

Background: Whole genome methylation sequencing (WGMS) in blood identifies extensive differential DNA methylation between persons who are cognitively unimpaired (CU) and those with late‐onset dementia due to Alzheimer’s disease (AD). Here we investigate differentially methylated positions (DMPs) in persons with mild cognitive impairment (MCI) compared to persons with and without AD.

Method: WGMS data quantified DNA methylation levels at 25,406,945 CpG loci in 382 blood samples from 99 persons with MCI, 109 persons with AD and 174 cognitively unimpaired persons in the Wisconsin Alzheimer’s Disease Research Center (WADRC) and the Wisconsin Registry for Alzheimer’s Prevention (WRAP).

Amyloid burden and APOE modify sex differences in estimated meta‐temporal region tau onset age.

Background: Recent advances in Alzheimer’s disease (AD) temporal biomarker modeling have revealed considerable heterogeneity in age at amyloid onset, and recently we and others identified sex and APOE differences in tau onset age and subsequent dementia development. Here we assessed whether amyloid burden, APOE‐e4 dose, and sex interact to predict estimated T+ onset age (ETOA).

Methods: Alzheimer’s Disease Neuroimaging Initiative participants (N = 911, Table 1) underwent serial PET imaging to quantify global cortical amyloid ([18F]Florbetapir SUVR50‐70, [18F]Florbetaben SUVR90‐110) and meta‐temporal tau ([18F]Flortaucipir SUVR80‐100) burden.

Leveraging a Novel Phenotype to Identify Complex Traits and Biological Pathways Associated with Resilience to Alzheimer’s Disease.

Background: Previous models of resilience to Alzheimer’s Disease (AD) have relied on cross‐sectional designs and inclusion of measures of neuropathology. Here, we present a novel modeling approach incorporating longitudinal data and the use of and higher order interaction terms to approximate neuropathological resilience, vastly increasing participant diversity and statistical power. We validate this approach and report novel genetic associations with neuropathological resilience.

Technology Use Amongst Older Adults with and without Cognitive Impairment: Results from the ‘Validation of Video Administration of a Modified UDSv3 Cognitive Battery (VCog)’ Study.

Background: Video interfacing is increasingly being used in research and health care. The ‘VCog’ Study seeks to determine whether remote research cognitive assessments are reliable and valid by directly comparing results from in‐person administration of a standardized cognitive battery to the same battery administered remotely by video. The study also assesses technology use and comfort amongst participants of varying levels of cognitive impairment.

Whole genome methylation sequencing in blood from persons with mild cognitive impairment and dementia due to Alzheimer's disease identifies cognitive status.

Introduction: Whole genome methylation sequencing (WGMS) in blood identifies differential DNA methylation in persons with late-onset dementia due to Alzheimer's disease (AD) but has not been tested in persons with mild cognitive impairment (MCI).

Methods: We used WGMS to compare DNA methylation levels at 25,244,219 CpG loci in 382 blood samples from 99 persons with MCI, 109 with AD, and 174 who are cognitively unimpaired (CU).

Results: WGMS identified 9756 differentially methylated positions (DMPs) in persons with MCI, including 1743 differentially methylated genes encoding proteins in biological pathways related to synapse organization, dendrite development, and ion transport.

Memory screening in the community: Facilitating earlier dementia diagnosis and care-Preliminary data.

Background: This program evaluation was conducted to assess the effectiveness of a community memory screening initiative across 25 Aging and Disability Resource Centers, spanning 39 counties and 5 tribal communities in the state of Wisconsin.

Methods: We evaluated the screened individuals' characteristics and reasons for screening, the screen results and topics addressed during screening, the rate of sending positive screens to primary care providers, and the incidence of subsequent dementia diagnosis as well as health behavior changes.

Results: Program evaluation results showed 791 completed surveys from individuals, indicating the program's accessibility and potential to reach populations in both urban and rural counties across Wisconsin.

Visual read of [F-18]florquinitau PET that includes and extends beyond the mesial temporal lobe is associated with increased plasma pTau217 and cognitive decline in a cohort that is enriched with risk for Alzheimer's disease.

Introduction: Patterns of signal from tau positron emission tomography (tau-PET) confined to the medial temporal lobe (MTL) or extended into the neocortex may be relevant for Alzheimer's disease (AD) research if they are linked to differential biomarker levels and cognitive decline.

Methods: Visual assessment of Tau-PET [F-18]florquinitau (FQT) exams from 728 initially non-demented older adults yielded four uptake groups: tau-negative (T-), MTL-only (T+), neocortex-only (T+), or both (T+). Mixed effects models assessed group differences in retrospective cognitive and plasma pTau217 trajectories.

Communicating Alzheimer's biomarker results to cognitively unimpaired research participants: Satisfaction, utility, and impact on research attitudes.

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).

Whole genome methylation sequencing in blood identifies extensive differential DNA methylation in late-onset dementia due to Alzheimer's disease.

Introduction: DNA microarray-based studies report differentially methylated positions (DMPs) in blood between late-onset dementia due to Alzheimer's disease (AD) and cognitively unimpaired individuals, but interrogate < 4% of the genome.

Methods: We used whole genome methylation sequencing (WGMS) to quantify DNA methylation levels at 25,409,826 CpG loci in 281 blood samples from 108 AD and 173 cognitively unimpaired individuals.

Results: WGMS identified 28,038 DMPs throughout the human methylome, including 2707 differentially methylated genes (e.

Anticipated Psychological or Behavioral Reactions to Learning Alzheimer Biomarker Results: Associations With Contextual Factors.

Background: As Alzheimer disease (AD) biomarker testing becomes more widely available, adults may opt to learn results. Considering potential reactions to learning biomarker results can guide prebiomarker and postbiomarker testing education and counseling programs.

Methods: Cognitively healthy adults enrolled in observational Alzheimer research responded to a telephone survey about learning AD risk information (n=334; 44% Black or African American; mean age=64.

Informing Disclosure: Efficacy of a Brief Educational Intervention on Research Participants' Knowledge about Alzheimer's Disease Biomarkers.

Recommendations for communicating Alzheimer's disease (AD) biomarkers include pre-disclosure participant education and counseling, to allow individuals to make an informed decision. In a cohort of largely non-Hispanic White, cognitively unimpaired older adults from the Wisconsin Registry for Alzheimer's Prevention, we conducted a structured amyloid PET disclosure process that included knowledge assessment and education. Baseline participant knowledge about AD biomarkers and research was high, but information needs existed around dementia causes, early AD symptoms, genetic information, and psychosocial consequences of disclosure.

Feasibility of virtual Alzheimer's biomarker disclosure: Findings from an observational cohort.

Introduction: 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.

Methods: 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.

Associations of the Lifestyle for Brain Health index with longitudinal cognition and brain amyloid beta in clinically unimpaired older adults: Findings from the Wisconsin Registry for Alzheimer's Prevention.

Introduction: Modifiable health and lifestyle factors increase risk of dementia, but whether modifiable factors, when measured in late-midlife, impact the emergence or progression of Alzheimer's disease (AD) pathophysiologic or cognitive changes remains unresolved.

Methods: In initially cognitively unimpaired, late middle-aged participants ( = 1215; baseline age, M [standard deviation] = 59.3 [6.

Implications of preclinical Alzheimer's disease biomarker disclosure for US policy and society.

Disclosure of Alzheimer's disease (AD) biomarkers to cognitively unimpaired adults are currently conducted only in research settings. Yet, US Food and Drug Administration approval of a disease-modifying treatment for symptomatic individuals, improved understanding of the "preclinical" phase of disease, and advancements toward more accessible biomarker tests suggest such disclosure will increase in frequency, eventually becoming routine in clinical practice. The changing landscape in AD research to focus on biomarkers has generated debate on the validity and clinical utility of disclosure to cognitively unimpaired adults.

Anticipated reactions to learning Alzheimer's disease biomarker results.

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.

Comparing emergency department use among individuals with varying levels of cognitive impairment.

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.

What Influences the Willingness of Blacks and African Americans to Enroll in Preclinical Alzheimer's Disease Biomarker Research? A Qualitative Vignette Analysis.

Background: Alzheimer's disease (AD) begins with an asymptomatic "preclinical" phase, in which abnormal biomarkers indicate risk for developing cognitive impairment. Research is increasingly focused on validating biomarkers to improve reliable diagnosis and timely clinical treatment of AD. Most preclinical biomarker research lacks adequate representation of Black/African American and other racially and ethnically minoritized individuals, limiting the applicability of data to these groups.

Cardiology clinic patient attitudes toward and potential personal utility of genetic testing: Findings from a unique multiracial clinical sample.

As more is understood about the hereditary nature of disease risk, the utility of genetic testing within cardiovascular medicine is increasingly being explored. Although testing may afford more personalized risk stratification, there is a paucity of information regarding patient knowledge, attitudes, and beliefs toward genetic testing among cardiology patients. Participants (n = 530) recruited primarily from a cardiology clinic filled out a 41-item written questionnaire assessing knowledge, beliefs, and attitudes toward genetic testing, motivators and detractors for considering genetic testing, and perceived likelihood for behavior change after hypothetical genetic testing risk stratification.

The Wisconsin Alzheimer's Institute Dementia Diagnostic Clinic Network: A community of practice to improve dementia care.

Background: The Wisconsin Alzheimer's Institute (WAI) Dementia Diagnostic Clinic Network is a community of practice formed in 1998 as a collaboration of community-based clinics from various healthcare systems throughout the state. Its purpose is to promote the use of evidence-based strategies to provide high quality care throughout Wisconsin for people with dementia. The purpose of this study is to describe the use of a community of practice to facilitate education of healthcare providers on best practices in dementia care, and the implementation of an interprofessional approach to diagnose and manage dementia and related disorders.

Moving beyond disclosure: Stages of care in preclinical Alzheimer's disease biomarker testing.

Alzheimer's disease (AD) begins with an asymptomatic "preclinical" phase, in which abnormal biomarkers indicate risk for developing cognitive impairment. Biomarker information is increasingly being disclosed in research settings, and is moving toward clinical settings with the development of cheaper and non-invasive testing. Limited research has focused on the safety and psychological effects of disclosing biomarker results to cognitively unimpaired adults.

Predictors of Willingness to Enroll in Hypothetical Alzheimer Disease Biomarker Studies that Disclose Personal Results.

Introduction: We examined factors related to willingness to enroll in hypothetical Alzheimer disease (AD) biomarker studies.

Methods: Using linear regression, we assessed the relationship among enrollment willingness and demographics, family dementia history, research attitudes, concern about AD, experiences of discrimination, and belief in AD risk modifiability. Inductive coding was used to assess qualitative data.