The new method reduces bias when race/ethnicity is partially, nonrandomly missing.
Background: Lower education has been reported to be associated with dementia. However, many studies have been done in settings where 12 years of formal education is the standard. Formal schooling in the Old Order Amish communities (OOA) ends at 8th grade, which along with their genetic homogeneity, makes it an interesting population to study the effect of education on cognitive impairment (CI). Objective: The objective of this study was to examine the association of education with cognitive function in individuals from the OOA. We hypothesized that small differences in educational attainment at lower levels of formal education were associated with risk for CI. Methods: Data of 2,426 individuals from the OOA aged 54–99 were analyzed. The Modified Mini-Mental State Examination (3MS-R) was used to classify participants as CI or normal. Individuals were classified in three education categories: <8, 8, and >8 years of education. To measure the association of education with cognitive status, a logistic regression model was performed adding age and sex as covariates. Results: Our results showed that individuals who attained lowest levels of education (<8 and 8) had a higher probability of becoming CI compared with people attending >8 years (OR = 2.96 and 1.85). Conclusion: Even within a setting of low levels of formal education, small differences in educational attainment can still be associated with the risk of cognitive impairment. Given the homogeneity of the OOA, these results are less likely to be biased by differences in socioeconomic backgrounds.
Introduction Puerto Ricans, the second largest Latino group in the continental US, are underrepresented in genomic studies of Alzheimer disease (AD). To increase representation of this group in genomic studies of AD, we developed a multisource ascertainment approach to enroll AD patients, and their family members living in Puerto Rico (PR) as part of the Alzheimer’s Disease Sequencing Project (ADSP), an international effort to advance broader personalized/precision medicine initiatives for AD across all populations. Methods The Puerto Rico Alzheimer Disease Initiative (PRADI) multisource ascertainment approach was developed to recruit and enroll Puerto Rican adults aged 50 years and older for a genetic research study of AD, including individuals with cognitive decline (AD, mild cognitive impairment), their similarly, aged family members, and cognitively healthy unrelated individuals age 50 and up. Emphasizing identification and relationship building with key stakeholders, we conducted ascertainment across the island. In addition to reporting on PRADI ascertainment, we detail admixture analysis for our cohort by region, group differences in age of onset, cognitive level by region, and ascertainment source. Results We report on 674 individuals who met standard eligibility criteria [282 AD-affected participants (42% of the sample), 115 individuals with mild cognitive impairment (MCI) (17% of the sample), and 277 cognitively healthy individuals (41% of the sample)]. There are 43 possible multiplex families (10 families with 4 or more AD-affected members and 3 families with 3 AD-affected members). Most individuals in our cohort were ascertained from the Metro, Bayamón, and Caguas health regions. Across health regions, we found differences in ancestral backgrounds, and select clinical traits. Discussion The multisource ascertainment approach used in the PRADI study highlights the importance of enlisting a broad range of community resources and providers. Preliminary results provide important information about our cohort that will be useful as we move forward with ascertainment. We expect that results from the PRADI study will lead to a better understanding of genetic risk for AD among this population.
Introduction Studies of cognitive impairment (CI) in Amish communities have identified sibships containing CI and cognitively unimpaired (CU) individuals. We hypothesize that CU individuals may carry protective alleles delaying age at onset (AAO) of CI. Methods A total of 1522 individuals screened for CI were genotyped. The outcome studied was AAO for CI individuals or age at last normal exam for CU individuals. Cox mixed‐effects models examined association between age and single nucleotide variants (SNVs). Results Three SNVs were significantly associated (P < 5 × 10–8) with AAO on chromosomes 6 (rs14538074; hazard ratio [HR] = 3.35), 9 (rs534551495; HR = 2.82), and 17 (rs146729640; HR = 6.38). The chromosome 17 association was replicated in the independent National Institute on Aging Genetics Initiative for Late‐Onset Alzheimer's Disease dataset. Discussion The replicated genome‐wide significant association with AAO on chromosome 17 is located in the SHISA6 gene, which is involved in post‐synaptic transmission in the hippocampus and is a biologically plausible candidate gene for Alzheimer's disease.
Background: Studies of cognitive impairment (CI) in Amish communities have identified sibships containing multiple CI and cognitively unimpaired (CU; unaffected after age 75) individuals. We hypothesize that these CU individuals may carry protective alleles delaying age at onset (AAO) of CI, preserving cognition in older age despite increased genetic risk. As well, the genetic and cultural isolation in the Amish since the early 1800s may have reduced the complexity of the genetic architecture of CI, increasing the power to detect protective alleles in this population. With this in mind we conducted a genome-wide study (GWAS) to identify loci associated with AAO of CI in a sample of Amish adults over age 75. Methods: 1,522 individuals aged 43-99 (mean age 73.1, 42% men) screened at least once for CI using the Modified Mini-Mental State exam (3MS) were genotyped using Illumina chipsets. Genotypes were imputed for 7,815,951 single nucleotide variants (SNV) with minor allele frequency (MAF) > 1%. The outcome studied was age, defined as 1) age at the first 3MS result indicating impairment (AAO; 3MS <87; 362 CI individuals) or 2) age at last normal exam (3MS >=87, 1,160 CU individuals). Cox mixed-effects models examined association between age and each SNV, adjusting for sex and familial relationships. To replicate genome-wide significant findings, SNVs in a 1 Megabase region centered on the peak SNV were examined for association with age using these same methods in the NIA-LOAD family study dataset (1,785 AD cases, 1,565 unaffected controls, mean age 73.5. Results: Three SNV were significantly associated (p<5 x 10-8) with AAO in the Amish, on chromosomes 6 (rs14538074; HR=3.35), 9 (rs534551495; HR=2.82), and 17 (rs146729640; Hazard Ratio (HR)=6.38). Each region found the common allele associated with later AAO. Replication analysis detected association at rs146729640, with nominal statistical significance (HR=1.49, p=0.02). Conclusions: The replicated genome-wide significant association with AAO on chromosome 17 suggest this may be novel locus associated with delayed onset of AD. The associated SNP is located in the SHISA6 gene, which is involved in post-synaptic transmission in the hippocampus and is a biologically plausible candidate gene for AD.
BackgroundWhile studying cognition in the Old Order Amish (OOA), we have observed strong performance on the constructional praxis delayed recall (CPDR) as compared to other cognitive tests, independent of overall cognitive status. This may indicate a preferential preservation of visuospatial memory in this population. Here, we investigate this by comparing the CPDR to the word list delayed recall (WLDR) within the OOA, as well as by comparing these results to a non-Amish cohort.Method420 OOA individuals in Indiana/Ohio age 66-95 who had complete data for the CPDR and WLDR were included. From the non-Amish CERAD cohort, 401 individuals age 60-96 with the same tests were included. For both cohorts, education-adjusted Z-scores were calculated for the CPDR and WLDR. The difference between the CPDR Z-score and the WLDR Z-score was calculated as a measure of the preservation of visuospatial memory over verbal memory. T-tests were first used to compare the tests within both cohorts and then stratified by case/control status. Linear regression was then used to investigate the effects of age, sex, cognitive status, and cohort on the Z-scores and difference between Z-scores. Additional t-tests and regressions were then performed to further investigate the effect of sex and its interaction with cohort.ResultWe found a significantly better performance on CPDR over WLDR in every cognitive status group in the OOA, but not in all groups of the CERAD cohort. After controlling for age, sex, and cognitive status, this preferential preservation remains significantly higher in the Amish, with being in the Amish cohort increasing the difference between Z-scores by an average of 0.615 units when compared to being in the CERAD cohort. When adjusting for age, sex, cognitive status, and cohort, the interaction between cohort and sex is significant, with the Amish males exhibiting a greater difference between Z-scores compared to other groups, with a significant interaction value of 0.676.DiscussionOverall, these findings suggest that the OOA preferentially preserve visuospatial memory over verbal memory, regardless of cognitive status. This effect is particularly strong in OOA males. In summary, this study gives additional evidence that the Amish exhibit unique patterns of memory loss and aging, with a preferential preservation of visuospatial memory over verbal memory. Additional studies are needed to further explain this phenomenon.
Alzheimer disease (AD) is the most common type of dementia and is currently estimated to affect 6.2 million Americans. It ranks as the sixth leading cause of death in the United States and the proportion of deaths due to AD has been increasing since the year 2000 while the proportion of many other leading causes of deaths have decreased or remained constant. The risk for AD is multifactorial, including genetic and environmental risk factors. Though APOE remains the largest genetic risk factor for AD, more than 26 other loci have been associated with AD risk. Here, we recruited from a population of Amish adults from Ohio and Indiana to investigate AD risk and protective genetic effects. With slightly lower incidence and later age of onset, it is thought that the Amish may hold protective genetic variants for AD. As a founder population that typically practices endogamy, variants that are rare in the general population may be at higher frequency in the Amish population. We characterized the genetic architecture of AD risk in the Amish and compared this to a non-Amish population, elucidating the lower relative importance of APOE and differing genetic architecture of the Amish compared to a general European ancestry population.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.