Variable frequency of LRRK2 variants in the Latin American research consortium on the genetics of Parkinson's disease (LARGE-PD), a case of ancestry

ABSTARCT: Mutations in Leucine-Rich Repeat Kinase 2 (LRRK2), primarily located in codons G2019 and R1441, represent the most common genetic cause of Parkinson's disease in European-derived populations. However, little is known about the frequency of these mutations in Latin American populations. In addition, a prior study suggested that a LRRK2 polymorphism (p.Q1111H) specific to Latino and Amerindian populations might be a risk factor for Parkinson's disease, but this finding requires replication. We screened 1734 Parkinson's disease patients and 1097 controls enrolled in the Latin American Research Consortium on the Genetics of Parkinson's disease (LARGE-PD), which includes sites in Argentina, Brazil, Colombia, Ecuador, Peru, and Uruguay. Genotypes were determined by TaqMan assay (p.G2019S and p.Q1111H) or by sequencing of exon 31 (p.R1441C/G/H/S). Admixture proportion was determined using a panel of 29 ancestry informative markers. We identified a total of 29 Parkinson's disease patients (1.7%) who carried p.G2019S and the frequency ranged from 0.2% in Peru to 4.2% in Uruguay. Only two Parkinson's disease patients carried p.R1441G and one patient carried p.R1441C. There was no significant difference in the frequency of p.Q1111H in patients (3.8%) compared to controls (3.1%; OR 1.02, p = 0.873). The frequency of LRRK2-p.G2019S varied greatly between different Latin American countries and was directly correlated with the amount of European ancestry observed. p.R1441G is rare in Latin America despite the large genetic contribution made by settlers from Spain, where the mutation is relatively common

Advancements in dementia research, diagnostics and care in Latin America : highlights from the 2023 Alzheimer's association international conference satellite symposium in Mexico City

While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics and care. In 2023, the Alzheimer’s Association hosted its eighth Satellite Symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. A wide range of topics were covered, including epidemiology, social determinants, dementia national plans, risk reduction, genetics, biomarkers, biobanks, and advancements in treatments. Large initiatives in the region including intra-country support showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care and implement affordable biomarkers in the region was highlighted

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Homocistinuria, una enfermedad metabólica de diagnóstico tardío en el Perú.

La Homocistinuria, es un desorden metabólico autosómico recesivo, cuya forma clásica es causada por deficiencia de cistationina β-sintasa, debido a mutaciones en el gen CBS (Cr 21q22.3). Se describe el caso de un varón de 17 años con hipopigmentación de piel y faneras, retraso psicomotor moderado, hábito marfanoide, miopía severa, subluxación del cristalino bilateral, que además presentó eventos psicóticos y una hemiparesia izquierda secundaria a un infarto lacunar. La determinación de homocisteína en plasma se encontró elevada (>9,9mg/dl), así como niveles altos de nitroprusiato de sodio en orina(4+) que confirmaron el diagnóstico clínico de homocistinuria. La homocistinuria clásica genera múltiples complicaciones a nivel dérmico, oftalmológico, cognitivo, osteoarticular y psiquiátrico; que podrían evitarse con un diagnóstico y tratamiento oportuno a través del tamizaje neonatal, aún no disponible en la mayoría de centros asistenciales en el Perú

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

Clinical profile of an Alzheimer´s disease cohort in the Peruvian population

Background Among older Peruvians (over 65‐years) the prevalence of dementia is 7%, with 56% meeting clinical criteria for Alzheimer Disease (AD). Peruvians, are an admixed population with approximately 80% Amerindian ancestral background. We have ascertained a cohort of Alzheimer Disease (AD) cases and cognitively intact controls for genetic studies. Method All participants have been recruited since 2019 using community outreach ascertainment strategies and hospital‐based recruitment from Lima, Peru. Cases were assessed by neurologist following NINDS/ADRDA criteria; and completed a comprehensive neurocognitive, neuropsychiatric and functional assessments. Controls were screened using MMSE, Clock drawing test and Pfeffer functional activities questionnaire. IRBs approvals from the participating Peruvian institutions and University of Miami were obtained for this study. Result A total of 102 AD cases (4 familial cases) and 152 controls were recruited since 2019 to December 2020. For AD cases: age at examination were 76.5±9.09, age at onset were 72.15±8.82, and 63.7% were female, average of 9.9±4.9 year of education. For controls: age at examination were 73.13±6.54, 62.5% were female, average of 11.62±4.41 year of education. Among cases diagnosis was classified as: 62.8% possible AD (two cases screened for Cerebrospinal fluid Abeta42 and tau protein levels) and 37.2% probable AD. Clinical and cognitive assessment profile for cases: MMSE average score was 17.2± 4.9 and Addenbrook’s Cognitive Examination average score was 38.5± 21.7 with memory loss predominance. Based on NPI the most frequent neuropsychiatric symptoms were irritability (51%), delusions (46%) and apathy (45%). Severity of dementia were assessed by CDR (CDR=3 for 33.9%, CDR=2 for 32.3%, CDR=1 for 24.2% and CDR=0.5 for 9.7%). Depressive symptoms were assessed with Geriatric Depression Scale with an average of 4.4±3.5 . Conclusion The clinical features of the AD cohort in the Peruvian population are consistent with previous reports. There is a tendency of a higher level of education in the control . Among the Peruvian AD cohort, the main neuropsychiatric symptoms are irritability, delusions and apathy consistent with the predominance of moderate to severe dementia. Reference: Marca V. et al. Dissecting the role of Amerindian genetic ancestry and ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population, Neurobiology of Aging, 2020

Prevalence of stroke survival in rural communities living in northern Peru. S1 Data

BACKGROUND AND PURPOSE: Stroke is the leading cause of neurological impairment in the South American Andean region. However, the epidemiology of stroke in the region has been poorly characterized. METHODS: We conducted a staged three-phase population-based study applying a validated eight-question neurological survey in 80 rural villages in Tumbes, northern Peru, then confirmed presence or absence of stroke through a neurologist's examination to estimate the prevalence of stroke. RESULTS: Our survey covered 90% of the population (22,278/24,854 individuals, mean age 30±21.28, 48.45% females), and prevalence of stroke was 7.05/1,000 inhabitants. After direct standardization to WHO's world standard population, adjusted prevalence of stroke was 6.94/1,000 inhabitants. Participants aged ≥85 years had higher stroke prevalence (>50/1000 inhabitants) compared to other stratified ages, and some unusual cases of stroke were found among individuals aged 25-34 years. The lowest age reported for a first stroke event was 16.8 years. High blood pressure (aPR 4.2 [2.7-6.4], p>0.001), and sedentary lifestyle (aPR 1.6 [1.0-2.6], p = 0.045) were more prevalent in people with stroke. CONCLUSIONS: The age-standardized prevalence of stroke in this rural coastal Peruvian population was slightly higher than previously reported in studies from surrounding rural South American settings, but lower than in rural African and Asian regions. The death rate from stroke was much higher than in industrialized and middle-income countries