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

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

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