The effect of years of schooling and age on CERAD-MX performance in Mexican preclinical carriers of the APP V717I mutation: Randomized data simulation.

INTRODUCTION: We aimed to determine the effect of years of schooling (YoS) and age on the Mexican adaptation of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-MX) scores in preclinical carriers group (PCG) and non-carriers group (NCG) of the APP V717I mutation. METHODS: We included 39 first-degree Mexican relatives of APP V717I carriers (PCG = 15; NCG = 24). We report eight CERAD-MX tasks: Mini-Mental State Examination (MMSE), Word List Learning (WLL), Delayed Recall (WLD) and Recognition (WLR), Constructional Praxis Copy (CPC) and Recall (CPR), Semantic Verbal Fluency (SVF), and Verbal Boston Naming (VBN), comparing both groups' performance and simulating new samples' random vectors by inverse transform sampling. RESULTS: PCG and NCG performed similarly on CERAD-MX. In both groups, YoS and age influence all z scores. A positive age effect resulted for PCG on CPC and SVF; for the NCG on MMSE, SVF, and VBN. DISCUSSION: All tasks are influenced by YoS. Higher YoS/younger age or YoS/older age interactions affected different tasks, suggesting that YoS confounds outcomes. Highlights: Years of schooling (YoS) and age affect the Mexican adaptation of the Consortium to Establish a Registry for Alzheimer's Disease scores of APP V717I preclinical carriers.Preclinical carriers underperformed non-carriers on Constructional Praxis Recall.Fewer YoS emerges as a confounding variable when detecting cognitive failures.Younger participants in both groups overperformed the older ones in the Memory tasks.Randomized data simulation increases statistical power when analyzing rare diseases.

Linear and Nonlinear Effect of Years of Schooling, Sex, and Age on the CERAD-MX and Complementary Tasks in a Mexican Sample: A Cross-Sectional Study.

OBJECTIVE: Since evidence of adults' cognition decline is based on standardized testing, we developed regression-based continuous norms by linear regression (LR) and nonlinear quantile regression (NQR) with years of schooling (YoS), age, and sex as covariates on the Mexican adaptation of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-MX) and complementary tasks. METHODS: 392 healthy, Spanish-speaking Mexican adults (50.25% women) aged 18-59 completed the 15 CERAD-MX cognitive tasks and complementary tasks. We used raw scores and examined YoS-related effects considering sex and age as covariates. For the NQR, we used calibrated scores for sex and age. While LR represents one line across the performance, NQR differentiated several nonlinear performance bands by quantiles. RESULTS: LR showed positive relationships between YoS and cognitive performance with a funnel variance pattern. Therefore, this relationship is better represented with NQR than LR. A small, but significant, negative effect of age was found for this age range (18-59 years). The band with fewer years of schooling (1-6) showed greater variability in the cognitive measures than those with more years of schooling (16-22). CONCLUSION: This study shows that NQR is useful for accurately positioning participants' performance relative to their peers. NQR accounts more than LR for the inconsistent variability of cognitive performance as a function of YoS by identifying the variability according to YoS (low, medium, high). Thus, NQR represents an appropriate way to construct norms for the cognitive performance of adults.

Attitudes about involvement in hypothetical clinical trial protocols in Mexican and Mexican-American at risk for autosomal dominant Alzheimer's disease.

BACKGROUND: The enrollment into clinical trials of persons at risk for autosomal dominant Alzheimer's disease (ADAD) in whom the onset of disease can be accurately predicted facilitates the interpretation of outcomes (e.g., biomarkers, treatment efficacy). Attitudes toward involvement in such studies are biased by intrinsic cultural and social characteristics. Our objective was to study how demographic factors such as country of residence, age, sex, schooling, parenthood, and urbanization affect attitudes towards participation in hypothetical clinical trials in Mexican families at risk for ADAD living either in Mexico or in the United States. METHODS: Participants were 74 members of different families known to harbor an ADAD mutation living in Mexico (n = 50) or in the United States (n = 24). Participants were asked, in a written questionnaire, their interest in participating in four hypothetical clinical trial scenarios of increasing perceived invasiveness. The questionnaire then asked about their willingness should there be a 50% chance of being assigned to a placebo group. The influences of demographic variables on decisions were performed using Wilcoxon rank-sum for continuous variables and Fisher's exact test for categorical variables. RESULTS: Participants who live in Mexico, who have or plan to have children, who do not attend or do not plan to attend school, and who live in rural areas gave more positive responses regarding their willingness to participate compared to those living in the U.S. The 50% chance of being in a placebo group increased the willingness to participate for family members living in Mexico. The main reason for participation was to help future generations, while the main reasons for refusal were not wanting to undergo genetic testing and consideration of adverse effects. CONCLUSIONS: We found a higher level of willingness to participate in clinical trials among persons living in rural Mexico and our data suggest that altruism towards future generations is a major motivation, though this was balanced against concerns regarding side effects. Our results emphasize the importance of sharing information and assessing its understanding in potential participants with diverse backgrounds in the nature of ADAD and regarding the design of clinical trials prior to their enrollment in such studies.

A mixed-methods study of cultural beliefs about dementia and genetic testing among Mexicans and Mexican-Americans at-risk for autosomal dominant Alzheimer's disease.

Trials to prevent autosomal dominantly inherited Alzheimer's disease (ADAD) are critical and timely. However, cultural beliefs about AD and genetic testing may preclude informed consent and participation, especially among racial/ethnic minorities. This mixed-methods study examines cultural beliefs about AD and genetic screening among at-risk populations of Mexican heritage. We surveyed 86 Mexican and 37 Mexican-American family members of patients with ADAD and interviewed 18 respondents in Mexico to explore perceptions and knowledge regarding AD and genetic testing. While most respondents understood that AD is inherited in their families, they also had limited understanding of the genetic mechanisms behind AD. Many believed that AD is a normal part of aging or that it is a mental illness caused by bad habits. However, beliefs that AD is caused by a curse or God's will were uncommon. The interviews demonstrated that very few at-risk respondents understood their own risk for harboring the mutation causing AD in their family. Once informed, most expressed a strong interest in genetic testing, largely motivated by the desire to be better prepared for the development of AD. Health professionals treating and investigators enrolling members from families with ADAD cannot assume that they fully understand the nature of the illness; therefore, providers should provide comprehensive information about ADAD and genetic testing.