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INTRODUCTION: Alzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (Aβ) active immunotherapy (vaccine) CAD106 and BACE‐1 inhibitor umibecestat in cognitively unimpaired 60‐ to 75‐year‐old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented. METHODS: Sixty‐five apolipoprotein E ε4 homozygotes with/without amyloid deposition received intramuscular CAD106 450 μg (n = 42) or placebo (n = 23) at baseline; Weeks 1, 7, 13; and quarterly; 51 of them had follow‐up Aβ positron emission tomography (PET) scans at 18 to 24 months. RESULTS: CAD106 induced measurable serum Aβ immunoglobulin G titers in 41/42 participants, slower rates of Aβ plaque accumulation (mean [standard deviation] annualized change from baseline in amyloid PET Centiloid: −0.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; P < 0.001), and three amyloid‐related imaging abnormality cases (one symptomatic). DISCUSSION: Despite early termination, these findings support the potential value of conducting larger prevention trials of Aβ active immunotherapies in individuals at risk for AD. Highlights: This was the first amyloid‐lowering prevention trial in persons at genetic risk of late‐onset Alzheimer's disease (AD).Active immunotherapy targeting amyloid (CAD106) was tested in this prevention trial.CAD106 significantly slowed down amyloid plaque deposition in apolipoprotein E homozygotes.CAD106 was generally safe and well tolerated, with only three amyloid‐related imaging abnormality cases (one symptomatic).Such an approach deserves further evaluation in larger AD prevention trials. [ABSTRACT FROM AUTHOR]

To identify factors that predict COVID-19 vaccination refusal and show how expectancies affect vaccination acceptance for non-vaccinated adults, we used a monthly repeated cross-sectional sample from June/2021 to October/2021 to collect data on vaccination behaviors and predictor variables for 2,116 US adults over 50 years of age. Selection bias modeling – which is required when data availability is a result of behavioral choice – predicts two outcomes: (1) no vaccination vs. vaccination for the entire sample and (2) the effects of expectancy indices predicting vaccination Refuser vs. vaccination Accepters for the unvaccinated group. Vaccine refusers were younger and less educated, endorsed common misconceptions about the COVID-19 epidemic, and were Black. Vaccination expectancies were related to vaccination refusal in the unvaccinated eligible group: negative expectancies increased vaccine refusal, while positive expectancies decreased it. We conclude that behavior-related expectancies (as opposed to more stable psychological traits) are important to identify because they are often modifiable and provide a point of intervention, not just for COVID-19 vaccination acceptance but also for other positive health behaviors. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Alzheimer's‐focused participant recruitment registries are tools for accelerating enrollment into studies, however, registry members are primarily White women. METHODS: We conducted a national online survey of 1501 adults ages 50–80, oversampling for Black and Hispanic/Latino respondents, assessing intention to join a generic "brain health" registry and to join a registry that required specific tasks. RESULTS: Intention to join a registry was low (M 3.48, SD 1.77), and lower than intention to join a registry requiring specific tasks. Intention was greatest for registries requiring completing surveys (M 4.70, SD 1.77). Differences in intention were primarily between White women and Black women; differences between other groups were limited to specific tasks required. DISCUSSION: The results indicate uncertainty about what a registry is, its purpose, and/or the concept of "brain health." Using the Reasoned Action Approach (RAA) to develop evidence‐based outreach messages describing a registry and required tasks may increase diversity. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV2 global pandemic impacted participants in the Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) clinical trial, who faced three stressors: 1) fear of developing dementia; 2) concerns about missing treatment; and 3) risk of SARS-CoV2 infection. Objective: To describe the frequency of psychological disorders among the participants of the API ADAD Colombia clinical study, treated by a holistic mental health team during the COVID-19 pandemic. The extent of use of mental health team services was explored considering different risk factors, and users and non-users of these services were compared. Methods: Participants had free and optional access to psychology and psychiatry services, outside of the study protocol. Descriptive statistics was used to analyze the frequency of the mental health difficulties. A multivariable logistic regression model has been used to assess associations with using this program. Results: 66 participants were treated by the Mental Health Team from March 1, 2020, to December 31, 2020. Before and after the start of the pandemic, the most common psychological problems were anxiety (36.4% before, 63.6% after) and depression (34.8% before, 37.9% after). 70% of users assisted by psychology and 81.6% of those assisted by psychiatry felt that the services were useful for them. Female sex, depression, and anxiety before the pandemic were positively associated with being assisted by either psychology or psychiatry, while the association with hyperlipidemia was negative. Conclusions: A holistic mental health program, carried out in the context of a study, could mitigate psychopathology during pandemics such as COVID-19. [ABSTRACT FROM AUTHOR]

Clinical trials for Alzheimer's disease (AD) are slower to enroll study participants, take longer to complete, and are more expensive than trials in most other therapeutic areas. The recruitment and retention of a large number of qualified, diverse volunteers to participate in clinical research studies remain among the key barriers to the successful completion of AD clinical trials. An advisory panel of experts from academia, patient‐advocacy organizations, philanthropy, non‐profit, government, and industry convened in 2020 to assess the critical challenges facing recruitment in Alzheimer's clinical trials and develop a set of recommendations to overcome them. This paper briefly reviews existing challenges in AD clinical research and discusses the feasibility and implications of the panel's recommendations for actionable and inclusive solutions to accelerate the development of novel therapies for AD. [ABSTRACT FROM AUTHOR]

A crucial aspect of any clinical trial is using the right outcome measure to assess treatment efficacy. Compared to the rapidly evolved understanding and measurement of pathophysiology in preclinical and early symptomatic stages of Alzheimer's disease (AD), relatively less progress has been made in the evolution of clinical outcome assessments (COAs) for those stages. The current paper aims to provide a benchmark for the design and evaluation of COAs for use in early AD trials. We discuss lessons learned on capturing cognitive changes in predementia stages of AD, including challenges when validating novel COAs for those early stages and necessary evidence for their implementation in clinical trials. Moving forward, we propose a multi‐step framework to advance the use of more effective COAs to assess clinically meaningful changes in early AD, which will hopefully contribute to the much‐needed consensus around more appropriate outcome measures to assess clinical efficacy of putative treatments. Highlights: We discuss lessons learned on capturing cognitive changes in predementia stages of AD.We propose a framework for the design and evaluation of performance based cognitive tests for use in early AD trials.We provide recommendations to facilitate the implementation of more effective cognitive outcome measures in AD trials. [ABSTRACT FROM AUTHOR]

Introduction: Females may have greater susceptibility to Alzheimer's disease (AD)‐pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively‐unimpaired Presenilin‐1 (PSEN1) E280A mutation carriers and non‐carriers. Methods: We analyzed baseline data from 167 mutation carriers and 75 non‐carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir‐ and fludeoxyglucose‐PET, MRI based hippocampal volume and cognitive testing. Results: Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant among PSEN1 mutation carriers only. APOE ε4 did not modify the effect of sex on AD biomarkers and memory. Discussion: Our findings suggest that, among cognitively‐unimpaired individuals at genetic risk for autosomal‐dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex‐specific differences in autosomal‐dominant AD is key to elucidating mechanisms of AD risk and resilience. [ABSTRACT FROM AUTHOR]

Background: There is a lack of racial, ethnic, and sex diversity in recruitment research registries and Alzheimer's disease (AD) research studies and trials. Theory-based recruitment messages may provide an opportunity to increase study participant diversity in AD research studies and trials. Objective: To identify behavioral, normative, and control beliefs that are associated with joining an AD-focused recruitment registry among historically underrepresented groups. Method: Using a Reasoned Action Approach, we conducted 60 semi-structured phone interviews in 2020 among White, Black, and Hispanic adults ages 49–79 years in Philadelphia, PA. Underlying beliefs were elicited for the target behavior of "signing up to be on a registry for brain health research studies in the next month." Percentages based on counts are reported for the overall sample and by race and ethnicity and sex. Results: Participants were most concerned that if they were to sign up for a registry, they would be asked to participate in experimental studies. Advancing science to help others was a commonly reported positive belief about signing up. Participants' children and friends/neighbors were important from a normative perspective. Barriers to enrollment focused on logistical concerns and inconvenient sign-up processes, including using a computer. Results show generally few racial and ethnic or sex group differences. Conclusion: The elicited beliefs from underrepresented groups offer a basis for understanding the behavior of signing up for research registries. However, there were few differences between the groups. Implications for outreach and recruitment are discussed. [ABSTRACT FROM AUTHOR]

This project examines the intersection of political constructs and epistemic motivations as they relate to belief in misinformation. How we value the origins of knowledge - through feelings and intuition or evidence and data - has important implications for our susceptibility to misinformation. This project explores how these epistemic motivations correlate with political ideology, party identification, and favorability towards President Trump, and how epistemic and political constructs predict belief in misinformation about COVID and the 2020 election. Results from a US national survey from Nov-Dec 2020 illustrate that Republicans, conservatives, and those favorable towards President Trump held greater misperceptions about COVID and the 2020 election. Additionally, epistemic motivations were associated with political preferences; Republicans and conservatives were more likely to reject evidence, and Trump supporters more likely to value feelings and intuition. Mediation analyses support the proposition that Trump favorability, Republicanism, and conservatism may help account for the relationships between epistemic motivations and misperceptions. Results are discussed in terms of the messaging strategies of right-wing populist movements, and the implications for democracy and public health. [ABSTRACT FROM AUTHOR]

Background With the onset of prevention trials for individuals at high risk for Alzheimer disease, there is increasing need for accurate risk prediction to inform study design and enrollment, but available risk estimates are limited. We developed risk estimates for the incidence of mild cognitive impairment (MCI) or dementia among cognitively unimpaired individuals by APOE-e4 dose for the genetic disclosure process of the Alzheimer's Prevention Initiative Generation Study, a prevention trial in cognitively unimpaired APOE-e4/e4 homozygote individuals. Methods and findings We included cognitively unimpaired individuals aged 60-75 y, consistent with Generation Study eligibility criteria, from the National Alzheimer's Coordinating Center (NACC) (n = 5,073, 158 APOE-e4/e4), the Rotterdam Study (n = 6,399, 156 APOE-e4/e4), the Framingham Heart Study (n = 4,078, 67 APOE-e4/e4), and the Sacramento Area Latino Study on Aging (SALSA) (n = 1,294, 11 APOE-e4/e4). We computed stratified cumulative incidence curves by age (60-64, 65-69, 70-75 y) and APOE-e4 dose, adjusting for the competing risk of mortality, and determined risk of MCI and/or dementia by genotype and baseline age. We also used subdistribution hazard regression to model relative hazard based on age, APOE genotype, sex, education, family history of dementia, vascular risk, subjective memory concerns, and baseline cognitive performance. The four cohorts varied considerably in age, education, ethnicity/race, and APOE-e4 allele frequency. Overall, cumulative incidence was uniformly higher in NACC than in the population-based cohorts. Among APOE-e4/e4 individuals, 5-y cumulative incidence was as follows: in the 60-64-y age stratum, it ranged from 0% to 5.88% in the three population-based cohorts versus 23.06% in NACC; in the 65-69-y age stratum, from 9.42% to 10.39% versus 34.62%; and in the 70-75-y age stratum, from 18.64% to 33.33% versus 38.34%. Five-year incidence of dementia was negligible except for APOE-e4/e4 individuals and those over 70 y. Lifetime incidence (to age 80-85 y) of MCI or dementia for the APOE-e4/e4 individuals in the long-term Framingham and Rotterdam cohorts was 34.69%-38.45% at age 60-64 y, 30.76%-40.26% at 65-69 y, and 33.3%-35.17% at 70-75 y. Confidence limits for these estimates are often wide, particularly for APOE-e4/e4 individuals and for the dementia outcome at 5 y. In regression models, APOE-e4 dose and age both consistently increased risk, as did lower education, subjective memory concerns, poorer baseline cognitive performance, and family history of dementia. We discuss several limitations of the study, including the small numbers of APOE-e4/e4 individuals, missing data and differential dropout, limited ethnic and racial diversity, and differences in definitions of exposure and outcome variables. Conclusions Estimates of the absolute risk of MCI or dementia, particularly over short time intervals, are sensitive to sampling and a variety of methodological factors. Nonetheless, such estimates were fairly consistent across the population-based cohorts, and lower than those from a convenience cohort and those estimated in prior studies-with implications for informed consent and design for clinical trials targeting high-risk individuals., Author(s): Jing Qian 1, Frank J. Wolters 2, Alexa Beiser 3,4, Mary Haan 5, M. Arfan Ikram 2, Jason Karlawish 6, Jessica B. Langbaum 7, John M. Neuhaus 5, Eric [...]

Background: COVID-19 vaccine uptake is an urgent public health priority.Purpose: To identify psychosocial determinants (attitudes, normative pressure, and perceived behavioral control) of COVID-19 vaccination intentions for U.S. White, Black, and Hispanic adults, and how COVID-19 misperceptions, beliefs about the value of science, and perceived media bias relate to these determinants.Methods: Longitudinal online survey using two national samples (18-49 years old/50 years and older), each stratified by racial/ethnic group (n = 3,190). Data were collected in October/November 2020 and were weighted by race group to be representative.Results: Path analyses showed that more positive attitudes about getting vaccinated predict intention across age and racial/ethnic groups, but normative pressure is relevant among older adults only. Belief in the value of science was positively associated with most determinants across all groups, however the association of COVID-19 misperceptions and perceived media bias with the determinants varied by age group.Conclusions: Messages that emphasize attitudes toward vaccination can be targeted to all age and racial/ethnic groups, and positive attitudes are universally related to a belief in the value of science. The varying role of normative pressure poses messages design challenges to increase vaccination acceptance. [ABSTRACT FROM AUTHOR]

Background: Recruiting cognitively‐unimpaired volunteers at high genetic risk of developing dementia into the Alzheimer's Prevention Initiative (API) Colombia trial, and maintaining study adherence for at least 5 years has been a monumental challenge. Major barriers included inclusion criteria, protocol visit schedule, long informed consent form (ICF), low levels of education of participants, misconceptions about participating in a clinical trial, and blinding to genetic status and treatment arm. We explain how our group went out of the conventional and traditional schemes of informed consent while adhering to good clinical practice and developed a novel approach to the consent process for potential candidates. Method: The identification, community education, and follow‐up of affected PSEN1 E280A families for the past three decades was the initial fundamental step to initiate a proper ICF process for the study. Then the launch of API Colombia Registry in 2010 was the base for appropriate preparation for the prevention trial. The process for API Colombia trial included step by step strategies, such as: a pre‐screening process developed by the team, pre‐consent informational meeting with the principal investigator in small groups of potential candidates, illustrated materials like a booklet titled "What I should know about informed consent and my decision to participate", and detailed infographics as a complementary material to main study ICF, use of a voluntary pre‐selection survey. The screening visit was divided in parts: discussion with the sub‐investigator about clinical trial participation, review of participant's questions, and signatures according to regulatory requirements. Result: From 623 potentially eligible registrants for pre‐screening, 319 were consented and underwent full eligibility screening and 252 were randomized. After eight years of study duration, 94% of participants completed the protocol, 90.5% completed the trial on treatment. Most participants who dropped out of the study did it due to incompatibility with work, unexpected pregnancy, or the decision to have children. Conclusion: We attribute successful trial adherence to the consent process that led to a well‐informed, voluntary, and responsible decision, and the participant's understanding of the unique contribution they can make to change the world by participating in clinical research. [ABSTRACT FROM AUTHOR]

Background: In most prevention clinical trials contraceptive use is required. The API ADAD Colombia Trial was a phase II, double‐blind, placebo‐controlled clinical trial to evaluate the safety and efficacy of the investigational product crenezumab. Trial period A was carried out from 2013 to 2021, during which 252 cognitively unimpaired PSEN1 E280A mutation carriers and non‐carriers were enrolled to be treated with crenezumab or placebo, including 159 women from 30 to 60 years of age. We describe strategies to address contraception in female volunteers. Method: For women of childbearing age, using two contraceptive methods and taking a pregnancy test before each administration of the investigational product was required. Different strategies were used to try to guarantee the adherence of the participants to the contraception methods: comprehensive educational activities, educational brochures, annual newsletters, medical advice on contraception methods and in some cases referral to a gynecology specialist to select the best contraception method. The General Fertility Rate (GFR) was used to evaluate the efficacy of the implemented strategies for contraceptive use. Using the parametric Welch's t‐test, we compared the GFR rates between trial volunteers and the Colombian population using data reported by the National Administrative Department of Statistics. Result: Tubectomy plus condom use 33.9% (54/159) and oral contraceptives plus condom use 15.1% (24/159) were the most common combinations used by volunteers. Ten women (6.3%) became pregnant during trial period A. Four of these pregnancies were due to therapeutic failure because at each visit the use of contraceptive methods was controlled and recorded in the medical history, three due to inappropriate contraceptive drug use reported by the participants, two were planned by the volunteers and one participant with difficulties in adherence to follow up visits. Significantly lower mean of GFR (p‐value = 2.68×10‐5) was observed in API ADAD volunteers compared to the Colombian population over the 7 years. Conclusion: According the p‐value obtained to compare the GFR between trial volunteers and the Colombian population, the strategies used to address contraception by the site were effective for the prevention of pregnancies. [ABSTRACT FROM AUTHOR]

Background: A number of extended families in Colombia with early‐onset ADAD have a PSEN1 mutation at codon 280 (E280A), comprise the largest ADAD kindred in the world. Trial participants have been treated with crenezumab (an experimental anti‐amyloid monoclonal antibody) or placebo. Topline results were presented in August, 2022 at AAIC. Although the trial did not demonstrate a statistically significant clinical benefit in either of its co‐primary endpoints, multiple statistical innovations were incorporated into this trial. Method: The API ADAD Colombia trial is a randomized, double‐blind, placebo‐controlled, parallel‐group phase 2b study evaluating the efficacy, safety, and tolerability of crenezumab in cognitively unimpaired ADAD PSEN1 E280A mutation carriers in Colombia (NCT01998841). Due to under enrollment and concerns with the sensitivity of the primary endpoint, the protocol was amended mid‐trial to change from 260 weeks of treatment to a common‐close design whereby treatment continued in the double‐blind portion until the last enrolled participant received 260 weeks of treatment. Because of the change in trial design and power considerations, the primary analysis was adapted from a traditional mixed model with repeated measures (MMRM) based analysis to a random coefficient regression model (RCRM) based analysis. To quantitatively examine the adequacy of the RCRM assumptions, a robust variance estimator (Huber 1967; White 1982) was prespecified as a sensitivity analysis to calculate the standard errors and p‐values of the co‐primary endpoints. This study used a type‐I‐error‐controlled statistical procedure to identify and elevate the Free and Cued Selective Reminding Test (FCSRT) cueing index to a co‐primary endpoint. To comprehensively assess the crenezumab effect across primary and secondary endpoints, the prespecified relative reduction point estimates along with the bootstrapped 95% confidence intervals were generated. Result: Innovative statistical methods in this trial will be presented. Conclusion: Although the API Colombia study did not meet its co‐primary endpoints, statistical learnings from this trial can benefit development of future AD trials. To further maximize the value of this unique trial dataset, participant‐level data will be made publicly available, including clinical, imaging, and biomarker data. Funding: NIA grants RF1‐AG041705, R01‐AG055444, Genentech, Roche, philanthropic contributions to Banner Alzheimer's Foundation. FlorbetapirPET was partly supported by Avid and Lilly. [ABSTRACT FROM AUTHOR]

Background: Registries have been proposed as a novel way to accelerate targeted recruitment for Alzheimer disease prevention clinical trials. However, there are limited data regarding registry effectiveness at accelerating recruitment and enrollment in research opportunities. This manuscript explores one site's experience with GeneMatch, a novel genetic registry for Alzheimer disease research.Methods: Referrals from GeneMatch to the site were tracked to understand the demographics of those referred and ultimate research enrollment outcomes. Referrals were cross-referenced with the site's existing recruitment database, to better understand the role of GeneMatch in the context of existing recruitment efforts.Results: GeneMatch referred 86 individuals to the site, resulting in 54 individuals coming into the site to pursue research involvement further. The majority of referrals (52/86, 60.47%) did not have prior contact with the site about research engagement, and having prior site contact did not significantly relate to engaging in on-site research.Conclusions: GeneMatch helped identify new individuals for participation in Alzheimer disease prevention studies. Results highlight the value of continuing local site-level efforts while also taking advantage of registries to enhance research recruitment. Ongoing efforts to further develop these and other novel strategies for outreach and engagement are much needed. [ABSTRACT FROM AUTHOR]

Neuropsychologists continue to face challenges when assessing Spanish-speaking individuals due to limited availability of normative data. We developed comprehensive normative data stratified by age and education for a Spanish neuropsychological test battery used by the Grupo de Neurociencias de Antioquia (Colombia) and the Colombian Alzheimer's Prevention Initiative Registry, which have followed large families at risk for autosomal-dominant Alzheimer's disease (ADAD) since the 1990s. Approximately 75% of these individuals are cognitively-unimpaired and are not genetically predisposed to develop ADAD. We conducted a retrospective study on neuropsychological evaluations from 2,673 cognitively unimpaired individuals (56% female), with ages ranging from 18 to 86 years and education from 1 to 25 years. Neuropsychological measures included the Consortium to Establish a Registry for Alzheimer's Disease-Colombia, and other multidomain Spanish tests. We examined associations between age, education, and sex with cognitive performance. Norms stratified by age and education are presented. Cognitive performance showed small associations with age and education and was unrelated to sex. We provided population-based norms for Spanish tests targeting multiple cognitive domains using a large Colombian sample. These normative data may be helpful for the neuropsychological characterization of Spanish speakers from Latin America in clinical and research settings. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive, neurodegenerative disease that creates complex challenges and a significant burden for patients and caregivers. Although underlying pathological changes due to AD may be detected in research studies decades prior to symptom onset, many patients in the early stages of AD remain undiagnosed in clinical practice. Increasing evidence points to the importance of an early and accurate AD diagnosis to optimize outcomes for patients and their families, yet many barriers remain along the diagnostic journey. Through a series of international working group meetings, a diverse group of experts contributed their perspectives to create a blueprint for a patient-centered diagnostic journey for individuals in the early stages of AD and an evolving, transdisciplinary care team. Here, we discuss key learnings, implications, and recommendations. [ABSTRACT FROM AUTHOR]

Background: Growing evidence suggests that there may be a sex-specific biological risk for Alzheimer's disease (AD). Individuals with autosomal dominant AD due to a mutation (E280A) in Presenilin-1 (PSEN1) are genetically determined to develop early-onset dementia and thus, have few age-related risk factors for AD that are known to vary by sex (i.e., cardiovascular disease, menopause, life expectancy).Objective: Investigate sex differences in markers of cognition and neurodegeneration in autosomal dominant AD.Methods: We conducted a retrospective study in 19 cognitively-unimpaired PSEN1 mutation carriers (age range 20-44; 11 females), 11 symptomatic carriers (age range 42-56; 8 females), and 23 matched non-carriers family members (age range 20-50; 13 females). We examined hippocampal volume ratio, CERAD Total Score, and CERAD Word List (i.e., Learning, Delayed Recall, and Recognition). Mann-Whitney U tests, Spearman correlations and regression models were conducted.Results: There were no differential associations between age, CERAD Total Score, CERAD Word List-Learning, Delayed Recall, Recognition, and hippocampal volume ratio in male and female carriers and non-carriers. Cognitively-unimpaired female carriers showed better CERAD Total scores and CERAD Word List-Learning than cognitively-unimpaired male carriers, despite having similar hippocampal volume ratios. The interaction of sex and hippocampal volume ratio did not predict cognitive performance across groups.Conclusion: Our preliminary findings suggest that cognitively-unimpaired female carriers showed a verbal memory reserve, and as disease progresses, female carriers did not exhibit a cognitive susceptibility to AD-related neurodegeneration. Future studies with larger samples of autosomal dominant AD are warranted to further understand sex differences in AD-related clinical and pathological markers. [ABSTRACT FROM AUTHOR]

Introduction: The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo‐controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60‐year‐old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non‐carriers who receive placebo. Methods: Of the 252 enrolled, we present data on a total of 242 mutation carriers and non‐carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. Results: We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non‐carriers, 30 to 53 years of age. Carriers were significantly younger than non‐carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. Discussion: Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non‐carriers. Their demographic characteristics are representative of the local population. [ABSTRACT FROM AUTHOR]