Lower Levels of Education Are Associated with Cognitive Impairment in the Old Order Amish

Ramos, Jairo; Chowdhury, Aneesa; Caywood, Laura J.; Prough, Michael; Fuzzell, M. Denise; Fuzzell, Sarada L.; Miskimen, Kristy; Whitehead, Patrice L.; Adams, Larry D.; Laux, Reneé; Song, Yeunjoo E.; Ogrocki, Paula; Lerner, Alan J.; Vance, Jeffery M.; Haines, Jonathan L.; Scott, William K.; Pericak‐Vance, Margaret A.; Cuccaro, Michael L.

doi:10.3233/jad-200909

Cited by 16 publications

(16 citation statements)

References 33 publications

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“…These occupations and life experiences could allow for additional non-formal education and practice with visuospatial tasks, resulting in a cognitive reserve specific to these visuospatial processes. This would be similar to evidence that links years of formal education with cognitive reserve, which protects against neurodegenerative disease (Farfel et al, 2013;Lövdén et al, 2020;Luerding et al, 2016;Ramos et al, 2021).…”

Section: Discussionsupporting

confidence: 73%

Preferential preservation of visuospatial memory over verbal memory in the Old Order Amish

et al. 2021

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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.

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Section: Discussionsupporting

confidence: 73%

Preferential preservation of visuospatial memory over verbal memory in the Old Order Amish

et al. 2021

Preprint

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“…Women were 58.3% of the sample. Individuals were residents of Amish communities in Ohio (Holmes County) and Indiana (Adams, Elkhart, and LaGrange counties) and recruited as previously described by Pericak-Vance et al (1996), Hahs et al (2006), Edwards et al (2013), Edwards et al (2014) and Ramos et al (2021). This is part of a population-based study of aging and age-related phenotypes such as AD performed by researchers from the University of Miami and Case Western Reserve University after Institutional Review Board (IRB) review and approval.…”

Section: Study Populations and Clinical Assessmentmentioning

confidence: 99%

“…A second strategy to improve power and reduce heterogeneity is to study a genetically homogenous population such as the Amish (Hahs et al, 2006). The Amish in the United States live in relatively genetically isolated communities (Hahs et al, 2006); members of these communities have participated in longitudinal studies of aging, cognition, and cognitive impairment for over two decades (Pericak-Vance et al, 1996) (Hahs et al, 2006) (Edwards et al, 2011) (Cummings et al, 2012) (Edwards et al, 2013) (D'Aoust et al, 2015) (Ramos et al, 2021) which have identified sibships with both individuals with CI and siblings that are cognitively unimpaired (CU). Our hypothesis is that individuals that are CU carry genetic variants that delay AAO of CI in spite of having an increased risk due to advanced age and family history of CI in a sibling.…”

Section: Introductionmentioning

confidence: 99%

Genetic variants in the SHISA6 gene are associated with delayed cognitive impairment in two family datasets

Ramos

et al. 2021

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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.

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“…These studies show that the age and gender differences of cognitive impairment were obvious, the cognitive impairment of the female elderly is more serious than that of the male, and the cognitive impairment of the older elderly is more serious than that of the younger elderly ( 15 , 16 ). And now there's evidence that the higher the education level or the longer duration of education they have, the lower chance of cognitive impairment happens in older adults, and vice versa ( 17 , 18 ). These factors were also relevant to cognitive impairment such as behavioral and lifestyle factors such as diet and exercise.…”

Section: Introductionmentioning

confidence: 99%

Correlates of cognitive impairment in the elderly in China: A cross-sectional study

Wang¹,

Zhang²,

Wang³

et al. 2022

Front. Public Health

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BackgroundTo identify correlates of the incidence of cognitive impairment among older Chinese populations through the use of logistic regression analysis-based decision tree approaches.MethodsCorrelates of cognitive impairment among older Chinese adults were identified through logistic regression analyses, with significant variables subsequently being incorporated into a decision tree analysis, with the CHAID method being employed for pre-pruning.ResultsThe risk score derived from the combination of logistic regression and decision tree analyses (0.237) was lower than that derived from a decision tree analysis alone (0.389). The primary factors related cognitive impairment in this patient population included age, gender, residence status, physical health status, and caring for grandchildren.ConclusionA combination of logistic regression and decision tree analyses can lower predicted risk scores, enabling the subdivision of populations with different characteristics and providing intuitive and specific insight regarding the effects of individual variables on predictive analyses. Overall, these results suggest that older adults in rural areas of China should be the focus of further cognitive impairment screening and interventions, particularly for older women.

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Lower Levels of Education Are Associated with Cognitive Impairment in the Old Order Amish

Cited by 16 publications

References 33 publications

Preferential preservation of visuospatial memory over verbal memory in the Old Order Amish

Preferential preservation of visuospatial memory over verbal memory in the Old Order Amish

Genetic variants in the SHISA6 gene are associated with delayed cognitive impairment in two family datasets

Correlates of cognitive impairment in the elderly in China: A cross-sectional study

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