6 research outputs found
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Impact of COVID‐19 in cognitively unimpaired individuals and dementia caregivers from the Peruvian Alzheimer Disease Initiative (PeADI)
Abstract Background The COVID‐19 pandemic has profoundly affected people’s lives worldwide. Stress and social restriction have a negative physical and psychological effect on people with dementia and their caregivers. Peru was one of the countries that experienced social restrictions and high rates of COVID‐19 morbidity and mortality. Methods We assessed the NIA‐NIH COVID‐19 impact survey for unrelated cognitively unimpaired (CU) individuals and caregivers from the PeADI cohort (case‐control genetic study for Alzheimer’s disease and related dementias) from five different regions across Peru. Results We analyzed 249 COVID‐19 impact surveys,65 dementia patient caregivers and 184 older CU individuals. Among caregivers, 86% felt isolated and 55.3% less connected with friends and family. 87.6% felt disrupted in everyday life, and 83% could not control the important things in their life. 44.6% found more difficult to provide care. The limitations on care include:physician appointments 64.6%,respite by family or friends 36.9%,day activity programs 32.35%, and overnight or extended‐stay respite care 16.9%. About 61.5% of them significantly reduced their household income. Almost 51% negatively changed their willingness to participate in clinical research if it required in‐person visits. Among the 184 CU individuals (mean age: 69.5± 3.8 years; 58.2% women). About 40.2% had new or worsening symptoms while thinking they had COVID‐19.About 60% were tested for Covid‐19 at least once, 29.3% were diagnosed with COVID‐19, and 2.1% were hospitalized. About 70% felt worried about getting or being reinfected by COVID‐19, 68.5% felt isolated from family and friends, 84.2% felt disrupted daily life, and 68.4% felt unable to control the important things in their life. About 60% had significantly reduced household income.About 52% of the CU noticed health changes (memory and thinking 31.2%, depression 42.7%, anxiety 51%, or behavior 46.8%).About 58% changed their willingness to participate in clinical research if it required in‐person visits. Conclusions Our results suggest that the COVID‐19 pandemic has affected dementia patient caregivers and CU individuals, both experienced variable changes in their mental health and significantly reduced household income.Caregivers have significant concerns regarding limited access to healthcare for their patients.CU individuals experienced fear of COVID‐19 reinfection.Further longitudinal surveys are required to explore changes in neuropsychiatric symptoms over time
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The Peruvian Alzheimer Disease Initiative (PeADI): An international effort model to increase diversity in AD research
Background
Peru is one of the five largest countries in Latin America and harboring a high Amerindian ancestry component in this population. The Latin American population, including Peruvians, are underrepresented in research studies of Alzheimer disease (AD).We have developed an international collaborative research initiative to ascertain a Peruvian cohort for AD and other related dementias for genetic studies of Amerindian individuals.
Methods
The Peruvian Alzheimer Disease initiative (PeADI) was developed to recruit and enroll Peruvian adults aged 65 and older to a comprehensive genetic AD study. Individuals will get whole genome sequencing and plasma biomarkers. Participants included cases with AD and ADD,healthy controls as well as multiplex AD families. Since 2019, we have established a multisource ascertainment approach including recruitment at main hospitals, outreach community activities and more recently due to the COVID19 pandemic remote recruitment and home visits. Our recruitment has expanded since our initial efforts in which we enrolled individuals from Lima, the capital city. We are now ascertaining participants in three regions from the Andes highlands (Puno,Huancayo, and Cusco) and one region from the southern coast (Tacna).All participants are enrolled using a standard protocol administered by neurologists and neuropsychologists. This protocol includes clinical interviews and neurocognitive assessment.
Results
As of December 2021, we have enrolled 103 AD and other dementia cases, 202 controls and 4 multiplex AD families. While the majority of participants are from Lima, 25% controls and 1% of cases have been recruited in regions outside Lima. We have confirmed a significant association between APOE and AD in Peruvian Population higher than we have observed in non‐Hispanics. In addition to ascertainment activities, we are working closely with the respective sites to develop a network for AD research across Peru. To date, we have developed local research capacities within each region,including training opportunities for investigators, coordinators and lab technicians. In addition, we are developing resources for health and medical support and basic equipment for all regions.
Conclusion
The PeADI study shows the importance of equitable international north‐south cooperation and local network cooperation to increase representation of understudied admixed populations to help us understand Amerindian ancestry in drug target discovery
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Exploring effect of known Alzheimer disease genetic loci in the Peruvian population
Background
Native American populations are substantially underrepresented in Alzheimer disease (AD) genetic studies. The Peruvian (PE) population with up to ∼80 of Amerindian ancestry (AI) provides a unique opportunity to assess the role of AI ancestry in AD. We performed whole‐genome sequencing in PE case‐control study to assess the effect of the known AD loci in PE population.
Methods
Whole‐genome sequencing was performed in 96 AD cases and 145 unrelated cognitive healthy controls from PE population. We calculated the global ancestry (principal components) using the EIGENSTRAT approach. We tested 21 AD lead variants from the recent large non‐Hispanic White (NHW) GWAS of AD (Kunkle et al. 2019). We performed association analyses using logistic regression model with accounting for age, gender, and population substructure (first three principal components). We used Bonferroni approach for multiple test correction.
Results
Logistic regression analysis confirmed association of APOE with AD (rs429358, OR=3.6, CI:1.9‐7.0; pv < 8.4e‐05) in PE population. CLU loci (rs9331896, pv=9.3e‐04) passed the significance threshold after Bonferroni multiple test correction. Two AD loci demonstrated nominal associations (pv<0.05), which were EPHA1 (rs10808026, pv = 0.028), and FERMT1 (rs17125924, pv=0.022) loci.
Conclusion
Our results showed that known AD APOE and CLU loci are significantly associated with AD in PE population. Some of the genes demonstrated suggestive associations, but further analysis with a larger sample size is on‐going to determine if these reflect true associations
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Admixed ancestral composition with Amerindian predominance at the Peruvian Alzheimer Disease Initiative (PeADI)
Background
Current genetic studies for AD and other dementias are making efforts to incorporate underrepresented populations including admixed Latinos. Peruvian population is characterized by admixed ancestry with a significant Amerindian component, which varies according to specific regions across Peru. The Peruvian Alzheimer Disease initiative (PeADI) was developed to ascertain a cohort for AD and other related dementias for genetic studies in Peru. We aim to determine the patterns of continental ancestry by regions across Peru.
Methods
Over the last 3 years, The PeADI study has recruited 212 unrelated cognitive participants through collaborative health centers and community outreach ascertainment strategies. Cases were assessed by neurologists following NINDS‐ADRDA criteria. Controls were screened using MMSE, Clock drawing test and Pfeffer functional activities questionnaire. Genome‐wide genotyping was performed by Illumina screening array. PC‐AiR and model‐based. The cohort was divided into five regions (Northern, Southern, Lima, Central Highlands, and Amazonian) based on place of birth of the participant or the ancient known ancestor.
Results
The global Admixture analysis showed that Peruvians have a substantial Amerindian component (63.6%), followed by European (35.9%), African (2.5%) and East Asian (2.1%) components. When analyzed by regions, we found that the Central region concentrates the highest Amerindian ancestry (72.7%), followed by the Northern region (58.2%), Lima and Callao (57%), the Amazonian region (55.6%), and the Southern region (55.1%). The highest European ancestry is located in the Amazonian region (42.1%), while the Central region has the lowest (26.6%). African and East Asian ancestry has little influence in Peru, being the Northern with the higher African component (4.1%), and Lima and Callao the region with the higher East Asian component (3.5%). There is no significant for Amerindian component across five regions (p=0.054); however, Central highlands region has higher Amerindian component compared to Lima (p=0.005), the Northern (p=0.005) and Southern(p=0.017) regions.
Conclusion
Our results confirmed the ancestry admixture of the Peruvian population with predominance of the Amerindian component. The Central region concentrates the highest Amerindian ancestry compared with other regions across Peru
Exploring the role of Amerindian genetic ancestry and ApoEε4 gene on Alzheimer disease in the Peruvian population
Background
The ApoEε4 allele is a major risk factor for AD whose effect shows strong racial/ethnic differences. Among the populations ApoE shows the strongest effect in East Asians (EA) (ε3/ε4 odds ratio OR: 3.1–5.6; ε4/ε4 OR: 11.8–33.1) and has a relatively lower effect in non‐Hispanic Whites (NHW) (ε3/ε4 OR: 3.2; ε4/ε4 OR: 14.9). The effect of ApoEε4 in populations with Amerindian (AI) ancestry is unknown. Peruvians with high AI (∼80%) genetic ancestry provide an opportunity to assess the effect of ApoEε4 in AD individuals with AI genetic ancestry. Our aim is to use data from the Peruvian population to assess the role of AI genetic ancestry and the ApoE gene on AD.
Method
Genotyping including both ApoE and Illumina GSA array was performed in 147 Peruvians (54 AD cases and 93 cognitively intact (CI) controls). PC‐AiR and model‐based ADMIXTURE approach inferred population structure. To assess local ancestry, phasing using SHAPEIT (with 1kGP reference) was followed by RFMix (HGDP reference panels). Association between affection status and ApoEε4 dose was analyzed using logistic regression, adjusting for age, gender, PC1‐3.
Result
Admixture analysis showed that Peruvians have a substantial AI (62%) ancestral component (31% European, 4% African and 3% EA genetic ancestry). AD individuals have higher frequency of ApoEε4 allele than CI individuals (7.4% vs 3.7%, respectively, p‐value = 3e‐4). Logistic regression analysis showed ApoEε4 dose significantly associated with AD in Peruvians (OR = 4.92, CI: 2.07‐12.83, p = 6e‐4). The average of the local ancestry proportions around the ApoE were close to the average global ancestry proportions (AI:56%, EU:37% and AF:7%).
Conclusion
Our results showed that the risk for AD from ApoEε4 in Peruvians is higher than we have observed in NHW populations. Given the high admixture of AI in the Peruvian population, it suggests that the AI local ancestry is contributing to a strong risk for AD in ApoEε4 carriers. This would align with the current believed migration pattern of AI from East Asia, where ApoEε4 carriers have the highest ApoEε4 risk for AD. Further ascertainment is ongoing to identify additional AI ApoEε4 carriers to directly ascertain risk
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A new risk locus on chromosome 1 is suggested by genome‐wide association study in Peruvians for Alzheimer disease
Abstract Background Increasing ethnic/ancestral diversity in genetic studies is critical for defining the genetic architecture of Alzheimer disease (AD). Amerindian (AI) populations are substantially underrepresented in AD genetic studies. The Peruvian (PE) population, with up to ∼80% of AI ancestry, provides a unique opportunity to assess the role of AI ancestry in AD. We performed the first genome‐wide association study (GWAS) in the PE population to identify novel AD susceptibility loci and characterize known AD genetic risk loci. Method The PE dataset includes array‐genotype and phenotype data from 542 individuals (189 cases; 353 controls), imputed to the NHLBI TOPMedv5 haplotype reference panel. We used a generalized linear mixed‐model (SAIGE software) for the GWAS analysis. We analyzed two separate models; the first model accounted for sex, age, and population substructure, while the second model also included the dosage of APOEe4. In both models, we included a genetic relationship matrix as a random effect to account for any potential relatedness. To determine if the associations are specific to specific ancestries, we employed ancestry‐aware approaches using the RFMix software. Result APOE was significantly associated with AD with an effect size comparable to that found in non‐Hispanic white (NHW) populations (OR = 3.3(2.2‐4.8),pv = 8.0×10 −10 ). Two additional known AD loci, TREML2 (pv = 0.008) and CLU (pv = 0.012), showed nominal significance Variants at three additional loci reached suggestive significance (pv<1×10 −6 ): NFASC (pv = 9.4×10 −8 ;chromosome 1), STK32A (pv = 9.3×10 −7 ; chromosome 5), and LOC100132830 (pv = 6.7×10 −7 ;chromosome 6). The NFASC locus neared genome‐wide significance in the APOE adjusted model (pv = 6.7×10 −8 ). The haplotypes associated with AD at the NFASC locus were found to be of European origin. Additionally, the STK32A locus was found to have a protective effect specifically among individuals of AI background. We did not observe significant heterogeneity of effect at the APOE and LOC100132830 loci across different ancestral backgrounds. Conclusion PE GWAS identified a novel, promising AD susceptibility locus in the NFASC gene of European origin. We also detected a potential protective effect in the STK32A locus on AI background, emphasizing the importance of incorporating ancestry‐aware approaches in gene discovery in admixed populations