A benchmark study on current GWAS models in admixed populations.

OBJECTIVE: The performances of popular genome-wide association study (GWAS) models have not been examined yet in a consistent manner under the scenario of genetic admixture, which introduces several challenging aspects: heterogeneity of minor allele frequency (MAF), wide spectrum of case-control ratio, varying effect sizes, etc. METHODS: We generated a cohort of synthetic individuals (N = 19 234) that simulates (i) a large sample size; (ii) two-way admixture (Native American and European ancestry) and (iii) a binary phenotype. We then benchmarked three popular GWAS tools [generalized linear mixed model associated test (GMMAT), scalable and accurate implementation of generalized mixed model (SAIGE) and Tractor] by computing inflation factors and power calculations under different MAFs, case-control ratios, sample sizes and varying ancestry proportions. We also employed a cohort of Peruvians (N = 249) to further examine the performances of the testing models on (i) real genetic and phenotype data and (ii) small sample sizes. RESULTS: In the synthetic cohort, SAIGE performed better than GMMAT and Tractor in terms of type-I error rate, especially under severe unbalanced case-control ratio. On the contrary, power analysis identified Tractor as the best method to pinpoint ancestry-specific causal variants but showed decreased power when the effect size displayed limited heterogeneity between ancestries. In the Peruvian cohort, only Tractor identified two suggestive loci (P-value $\le 1\ast{10}^{-5}$) associated with Native American ancestry. DISCUSSION: The current study illustrates best practice and limitations for available GWAS tools under the scenario of genetic admixture. Incorporating local ancestry in GWAS analyses boosts power, although careful consideration of complex scenarios (small sample sizes, imbalance case-control ratio, MAF heterogeneity) is needed.

Epidemiology of neurocognitive disorders in adults from urban-marginalized areas: a door-to-door population-based study in Puente Piedra, Lima, Peru.

Background: In Latin America (LA), the prevalence of dementia is expected to triple to 150 million people by 2050. The 2020 Lancet Commission report identified several modifiable dementia risk factors, yet few social and environmental factors, most relevant to vulnerable regions of LA, were highlighted in this report. We sought to assess the epidemiology of neurocognitive disorders (NCD) in Puente Piedra, one of the most socially and economically vulnerable districts of Lima, the capital of Peru. Methodology: This was a cross-sectional door-to-door observational study that used two-stage household sampling. One young adult (30-59 years) and one older adult (>60 years) per household were enrolled. We collected demographic, clinical, and neurocognitive data. Addenbrooke's Cognitive Examination (young adults) and the RUDAS-PE (older adults) were used, classifying participants as cognitively normal, possible mild NCD, or possible major NCD. Results: We enrolled 247 participants (median age 46 years; 67% female). One-fourth had not completed secondary school and more than 50% completed only secondary school. Most participants were housewives (46%) and 21% did not have health insurance. The overall prevalence of possible NCD was 30% (25.6 and 41.8% among younger adults and older adults, respectively). Among younger adults, those ages 55-59 years more frequently had NCD (70%) compared to younger age ranges. Among older adults, only 3 subjects (4.5%) had major NCD. Conclusion: We found a high frequency of possible NCDs in a socially and economically vulnerable community in Lima, Peru, with younger adults showing levels of NCD higher than expected. Our findings support the need for health systems to incorporate cognitive screenings programs for NCD in younger ages. Future research on NCD would include younger populations, particularly in vulnerable communities.

The Memory Alteration Test Is Correlated with Clinical, Cerebrospinal Fluid, and Brain Imaging Markers of Alzheimer Disease in Lima, Peru.

INTRODUCTION: As disease-modifying therapies become available for Alzheimer's disease (AD), detection of AD in early stages of illness (mild cognitive impairment [MCI], early dementia) becomes increasingly important. Biomarkers for AD in low- and middle-income countries (LMICs) are costly and not widely available; hence, it is important to identify cognitive tests that correlate well with AD biomarker status. In this study, we evaluated the memory alteration test (M@T) to detect biomarker-proven AD and quantify its correlation with neurodegeneration and cerebrospinal fluid (CSF) AD biomarkers in a cohort of participants from Lima, Peru. METHODS: This is a secondary analysis of a cohort of 185 participants: 63 controls, 53 with amnestic MCI (aMCI), and 69 with dementia due to AD. Participants underwent testing with M@T and a gold standard neuropsychological battery. We measured total tau (t-tau), phosphorylated tau (p-tau), and beta-amyloid (ß-amyloid) in CSF, and evaluated neurodegeneration via medial temporal atrophy score in MRI. We used receiver-operator curves to determine the discriminative capacity of the total M@T score and its subdomains. We used the Pearson coefficient to correlate M@T score and CSF biomarkers. RESULTS: The M@T had an area under the curve (AUC) of 0.994 to discriminate between controls and cognitively impaired (aMCI or AD) patients, and an AUC of 0.98 to differentiate between aMCI and AD patients. Free-recall and cued recall had the highest AUCs of all subdomains. Total score was strongly correlated with t-tau (-0.77) and p-tau (-0.72), and moderately correlated with ß-amyloid (0.66). The AUC for discrimination of neurodegeneration was 0.87. CONCLUSION: The M@T had excellent discrimination of aMCI and dementia due to AD. It was strongly correlated with CSF biomarkers and had good discrimination of neurodegeneration. In LMICs, the M@T may be a cost-effective screening tool for aMCI and dementia caused by AD.

Diagnóstico de la variante conductual de demencia frontotemporal basado en estadios clínicos adaptado para países con baja educación: el caso de Perú

Demencia frontotemporal (DFT) es una condición neurodegenerativa escasamente reconocida en personas menores a 65 años de edad. El diagnóstico de DFT variante conductual (DFTvc) se basa en una entrevista clínica comprehensiva, complementada por una evaluación multidimensional (neurológica, cognitiva, neuropsiquiátrica, de biomarcadores e imágenes cerebrales) adaptada y validada a la población a estudiar; sin embargo, a pesar del incremento de su prevalencia en Latinoamérica y el Caribe, existe necesidad de herramientas estandarizadas y un consenso para el diagnóstico de DFTvc. El artículo intenta realizar una aproximación del enfoque de diagnóstico de DFTvc en escenario de paises con bajos y medianos ingresos, como el Perú.

Frontotemporal dementia (FTD) is a widely recognized neurodegenerative condition in people under 65 years old. The diagnosis of behavioral variant FTD (bvFTD) is based on a comprehensive clinical assessment, complemented by a multidimensional assessment (neurological, cognitive, neuropsychiatric, biomarker and brain imaging) adapted and validated to the population to be studied; however, despite its increasing prevalence in Latin America and the Caribbean, there is a need for standardized tools and consensus for the bvFTD diagnosis. The manuscript attempts to approximate the approach for the diagnosis of bvFTD in the setting of low and middle-income countries, including Peru.

A benchmark study on current GWAS models in admixed populations.

Objective: The performances of popular Genome-wide association study (GWAS) models haven't been examined yet in a consistent manner under the scenario of genetic admixture, which introduces several challenging aspects such as heterogeneity of minor allele frequency (MAF), a wide spectrum of case-control ratio, and varying effect sizes etc. Methods: We generated a cohort of synthetic individuals (N=19,234) that simulates 1) a large sample size; 2) two-way admixture [Native American-European ancestry] and 3) a binary phenotype. We then examined the inflation factors produced by three popular GWAS tools: GMMAT, SAIGE, and Tractor. We also computed power calculations under different MAFs, case-control ratios, and varying ancestry percentages. Then, we employed a cohort of Peruvians (N=249) to further examine the performances of the testing models on 1) real genetic data and 2) small sample sizes. Finally, we validated these findings using an independent Peruvian cohort (N=109) included in 1000 Genome project (1000G). Results: In the synthetic cohort, SAIGE performed better than GMMAT and Tractor in terms of type-I error rate, especially under severe unbalanced case-control ratio. On the contrary, power analysis identified Tractor as the best method to pinpoint ancestry-specific causal variants, but showed decreased power when no adequate heterogeneity of the true effect sizes was simulated between ancestries. The real Peruvian data showed that Tractor is severely affected by small sample sizes, and produced severely inflated statistics, which we replicated in the 1000G Peruvian cohort. Discussion: The current study illustrates the limitations of available GWAS tools under different scenarios of genetic admixture. We urge caution when interpreting results under complex population scenarios.

Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS): Study design and harmonization.

INTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.

Impact of COVID-19 Mandatory Lockdown Measures on Cognitive and Neuropsychiatric Symptoms in Persons with Alzheimer's Disease in Lima, Peru.

BACKGROUND: Neuropsychiatric symptoms (NPS) in patients with Alzheimer's disease (AD) worsened during the COVID-19 lockdowns, but their progression thereafter is unknown. We present the first longitudinal study tracking them before, during, and after restrictions. OBJECTIVES: To describe the effect of the COVID-19 mandatory lockdowns on Cognitive and Neuropsychiatric symptoms in patients with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). METHODS: Cohort of 48 patients with amnestic MCI and 38 with AD in Lima, Peru. They received three rounds of cognitive (RUDAS, CDR, M@T), behavioral (NPI), and functional (ADCS-ADL) assessments. We assessed the change in score means across the time points and for each domain of NPS and tracked the changes in individual patients. RESULTS: RUDAS declined 0.9 (SD 1.0) from baseline to lockdown and 0.7 (SD 1.0) after restrictions. M@T declined 1.0 (SD 1.5) from baseline to lockdown and 1.4 (SD 2.0) after restrictions. CDR worsened in 72 patients (83.72%) from baseline to post-lockdown. NPI worsened by 10 (SD 8.3) from baseline to lockdown but improved by 4.8 (SD 6.4) after restrictions. Proportionally, 81.3% of all patients had worsened NPS during the lockdowns, but only 10.7% saw an increase thereafter. Improvement was statistically significant for specific NPS domains except hallucinations, delusions, and appetite changes. Anxiety, irritability, apathy, and disinhibition returned to baseline levels. CONCLUSION: Following confinement, cognition continued to decline, but NPS demonstrated either stability or improvement. This highlights the role modifiable risk factors may have on the progression of NPS.

Combining visual rating scales to identify prodromal Alzheimer's disease and Alzheimer's disease dementia in a population from a low and middle-income country.

Background: Many low- and middle-income countries, including Latin America, lack access to biomarkers for the diagnosis of prodromal Alzheimer's Disease (AD; mild cognitive impairment due to AD) and AD dementia. MRI visual rating scales may serve as an ancillary diagnostic tool for identifying prodromal AD or AD in Latin America. We investigated the ability of brain MRI visual rating scales to distinguish between cognitively healthy controls, prodromal AD and AD. Methods: A cross-sectional study was conducted from a multidisciplinary neurology clinic in Lima, Peru using neuropsychological assessments, brain MRI and cerebrospinal fluid amyloid and tau levels. Medial temporal lobe atrophy (MTA), posterior atrophy (PA), white matter hyperintensity (WMH), and MTA+PA composite MRI scores were compared. Sensitivity, specificity, and area under the curve (AUC) were determined. Results: Fifty-three patients with prodromal AD, 69 with AD, and 63 cognitively healthy elderly individuals were enrolled. The median age was 75 (8) and 42.7% were men. Neither sex, mean age, nor years of education were significantly different between groups. The MTA was higher in patients with AD (p < 0.0001) compared with prodromal AD and controls, and MTA scores adjusted by age range (p < 0.0001) and PA scores (p < 0.0001) were each significantly associated with AD diagnosis (p < 0.0001) but not the WMH score (p=0.426). The MTA had better performance among ages <75 years (AUC 0.90 [0.85-0.95]), while adjusted MTA+PA scores performed better among ages>75 years (AUC 0.85 [0.79-0.92]). For AD diagnosis, MTA+PA had the best performance (AUC 1.00) for all age groups. Conclusions: Combining MTA and PA scores demonstrates greater discriminative ability to differentiate controls from prodromal AD and AD, highlighting the diagnostic value of visual rating scales in daily clinical practice, particularly in Latin America where access to advanced neuroimaging and CSF biomarkers is limited in the clinical setting.

A Functional Assessment Tool to Distinguish Controls From Alzheimer's Disease in Lima, Peru.

BACKGROUND: The Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale is a versatile functional assessment tool for patients with Alzheimer's disease (ad). We evaluated its performance in controls, Peruvians with MCI or AD. METHODS: A cross-sectional study of older adults attending a neurology institute in Lima (Peru) with mild cognitive impairment (MCI), ad or cognitively healthy. Test-retest reliability (intraclass correlation coefficient, ICC; internal consistency, Cronbach's alpha) and validity were assessed. RESULTS: We enrolled 276 individuals (ad: 113, MCI: 68, controls: 95) with no age, sex, educational level, and depressive symptom differences. Reliability was ideal (ICC: .996), and Cronbach's alpha was adequate (.937). The ADCS-ADL could not differentiate MCI from controls but did differentiate ad severity. The ADCS-ADL correlated highly with nearly all tools. CONCLUSIONS: The ADCS-ADL scale is reliable in a population with ad in Lima, Peru. Future work may validate a tool for Peruvians with lower educational levels.

Validation of Picture Free and Cued Selective Reminding Test for Illiteracy in Lima, Peru.

Dementia in Latin America is a crucial public health problem. Identifying brief cognitive screening (BCS) tools for the primary care setting is crucial, particularly for illiterate individuals. We evaluated tool performance characteristics and validated the free and total recall sections of the Free and Cued Selective Reminding Test-Picture version (FCSRT-Picture) to discriminate between 63 patients with early Alzheimer's disease dementia (ADD), 60 amnestic mild cognitive impairment (aMCI) and 64 cognitively healthy Peruvian individuals with illiteracy from an urban area. Clinical, functional, and cognitive assessments were performed. FCSRT-Picture performance was assessed using receiver operating characteristic curve analyses. The mean ± standard deviation scores were 7.7 ± 1.0 in ADD, 11.8 ± 1.6 in aMCI, and 29.5 ± 1.8 in controls. The FCSRT-Picture had better performance characteristics for distinguishing controls from aMCI compared with several other BCS tools, but similar characteristics between controls and early ADD. The FCSRT-Picture is a reliable BCS tool for illiteracy in Peru.

Estudio comparativo de la capacidad denominativa y la memoria episódica de los pacientes con demencia degenerativa / Comparative Study of the Word Capacity and Episodic Memory of Patients with Degenerative Dementia

RESUMEN Introducción: Aunque la ausencia de deterioro de la memoria se consideró entre los criterios diagnósticos para diferenciar la enfermedad de Alzheimer (EA) de la demencia frontotemporal variante conductual (DFTvC), la evidencia actual, en aumento, sería la un importante porcentaje de casos de DFTvC con déficits de la memoria episódica. El presente estudio se diseñó con el fin de comparar el perfil de desempeño de la capacidad denominativa y de la memoria episódica de los pacientes con EA y DFTvC. Métodos: Estudio transversal y analítico con grupo de control (n = 32). Se incluyó a 42 sujetos con probable EA y 22 con probable DFTvC, todos mayores de 60 años. Se utilizaron instrumentos del Uniform Data Set validados en español: Multilingual Naming Test (MINT), historia de Craft-21 y Figura compleja de Benson, entre otros. Resultados: Se observó un mayor promedio de edad entre los pacientes con EA. La capacidad denominativa fue mucho menor en los pacientes con DFTvC que en aquellos con EA, medida según el MINT y el coeficiente de denominación sustantivos/verbos. Todos los pacientes con DFTvC, el 73,81% de aquellos con EAy solo el 31,25% de los controles no lograron reconocer la Figura compleja de Benson. Todas las diferencias fueron estadísticamente significativas (p< 0,001). Resultados: Este estudio confirma el perfil amnésico de los pacientes con EA y revela la disminución de la capacidad denominativa de los pacientes con DFTvC, un área del lenguaje que se afecta típica y tempranamente con las funciones ejecutivas, según recientes hallazgos. Conclusiones: Los pacientes con EA rinden peor en las tareas de memoria episódica verbal y visual, mientras que los pacientes con DFTvC rinden peor en tareas de denominación. Estos hallazgos abren la posibilidad de explorar los mecanismos de participación prefrontal en la memoria episódica, típicamente atribuida al hipocampo.

ABSTRACT Introduction: Although the absence of memory impairment was considered among the Alzheimer's disease diagnostic criteria to differentiate Alzheimer's disease (AD) from Behavioural Variant of Frontotemporal dementia Frontotemporal Dementia (bvFTD), current and growingevidence indicates that a significant Neuropsychological assessment percentage of cases of bvFTD present with episodic memory deficits. In order to compare Memory the performance profile of the naming capacity and episodic memory in patients with AD and bvFTD the present study was designed. Methods: Cross-sectional and analytical study with control group (32 people). The study included 42 people with probable AD and 22 with probable bvFTD, all over 60 years old. Uniform Data Set instruments validated in Spanish were used: Multilingual Naming Test (MINT), Craft-21 history and Benson's complex figure, among others. Results: A higher average age was observed among the patients with AD. The naming capacity was much lower in patients with bvFTD compared to patients with AD, measured according to the MINT and the nouns/verbs naming coefficient. All patients with bvFTD, 73.81% of those with AD and only 31.25% of the control group failed to recognise Benson's complex figure. All differences were statistically significant (p < 0.001). Results:This study confirms the amnesic profile of patients with AD and reveals the decrease in naming capacity in patients with bvFTD, an area of language that is typically affected early on with executive functions, according to recent findings. Conclusions: Patients with AD perform worse in verbal and visual episodic memory tasks, while patients with bvFTD perform worse in naming tasks. These findings open the possibility of exploring the mechanisms of prefrontal participation in episodic memory, typically attributed to the hippocampus.

Comparative study of the word capacity and episodic memory of patients with degenerative dementia.

INTRODUCTION: Although the absence of memory impairment was considered among the diagnostic criteria to differentiate Alzheimer's disease (AD) from Behavioural Variant of Frontotemporal Dementia (bvFTD), current and growing evidence indicates that a significant percentage of cases of bvFTD present with episodic memory deficits. In order to compare the performance profile of the naming capacity and episodic memory in patients with AD and bvFTD the present study was designed. METHODS: Cross-sectional and analytical study with control group (32 people). The study included 42 people with probable AD and 22 with probable bvFTD, all over 60 years old. Uniform Data Set instruments validated in Spanish were used: Multilingual Naming Test (MINT), Craft-21 history and Benson's complex figure, among others. RESULTS: A higher average age was observed among the patients with AD. The naming capacity was much lower in patients with bvFTD compared to patients with AD, measured according to the MINT and the nouns/verbs naming coefficient. All patients with bvFTD, 73.81% of those with AD and only 31.25% of the control group failed to recognise Benson's complex figure. All differences were statistically significant (p < 0.001). RESULTS: This study confirms the amnesic profile of patients with AD and reveals the decrease in naming capacity in patients with bvFTD, an area of ​​language that is typically affected early on with executive functions, according to recent findings. CONCLUSIONS: Patients with AD perform worse in verbal and visual episodic memory tasks, while patients with bvFTD perform worse in naming tasks. These findings open the possibility of exploring the mechanisms of prefrontal participation in episodic memory, typically attributed to the hippocampus.

Diagnostic accuracy of brief cognitive screening tools to diagnose vascular cognitive impairment in Peru.

INTRODUCTION: To evaluate the diagnostic accuracy of three brief cognitive screening (BCS) tools, Peruvian version of Addenbrooke's Cognitive Examination (ACE-Pe), of INECO Frontal Screening (IFS-Pe) and of the Mini-Mental State Examination (MMSE-Pe), for the diagnosis of vascular cognitive impairment (VCI) and its non-dementia stages (VCI-ND) and vascular dementia (VD) in patients with cerebral stroke in Lima-Peru. MATERIALS AND METHODS: A cohort analysis to evaluate the diagnostic accuracy of three BCS for VCI. RESULTS: Two hundred and four patients were evaluated: 61% Non-VCI, 30% VCI-ND and 9% VD. To discriminate patients with VCI from controls, the area under the curve (AUC) of ACE-Pe, IFS-Pe and MMs-Pe were 0.99 (95% confidence interval [CI] 0.98-0.99), 0.99 (95%CI 0.98-0.99) and 0.87 (95%CI 0.82-0.92), respectively. Of the three BCS, the IFS-Pe presented a larger AUC to discriminate VCI-ND from VD (AUC = 0.98 [95%CI 0.95-1]) compared to ACE-Pe (AUC = 0.84 [95%CI 0.74-0.95]) and MMSE-Pe (0.92 [95%CI 0.86-0.99]). The IFS-Pe presented a higher sensitivity (S), specificity (Sp), and positive (+LR) and negative likelihood ratios (-LR) (S = 96.72%, Sp = 89.47%, +LR = 9.1 and -LR = 0.03) than ACE-Pe (S = 96.72%, Sp = 63.16%, +LR = 2.62 and -LR = 0.05) and MMSE-Pe (S = 90.16%, Sp = 78.95%, +LR = 4.28 and -LR = 0.12). In the multiple regression analysis, the IFS-Pe was not affected by age, sex or years of schooling. CONCLUSION: The IFS-Pe has the best diagnostic accuracy for detecting VCI and discriminating between pre-dementia (VCI-ND) and dementia (VD) stages.

Social Cognition and Behavioral Assessments Improve the Diagnosis of Behavioral Variant of Frontotemporal Dementia in Older Peruvians With Low Educational Levels.

Background: The behavioral variant of frontotemporal dementia (bvFTD), characterized by early behavioral abnormalities and late memory impairment, is a neurodegenerative disorder with a detrimental impact on patients and their caregivers. bvFTD is often difficult to distinguish from other neurodegenerative diseases, such as Alzheimer's disease (AD), using brief cognitive tests. Combining brief socio-cognitive and behavioral evaluations with standard cognitive testing could better discriminate bvFTD from AD patients. We sought to evaluate the diagnostic accuracy of brief socio-cognitive tests that may differentiate bvFTD and AD patients with low educational levels. Methods: A prospective study was performed on 51 individuals over the age of 50 with low educational levels, with bvFTD or AD diagnosed using published criteria, and who were receiving neurological care at a multidisciplinary neurology clinic in Lima, Peru, between July 2017 and December 2020. All patients had a comprehensive neurological evaluation, including a full neurocognitive battery and brief tests of cognition (Addenbrooke's Cognitive Examination version III, ACE-III), social cognition (Mini-social Cognition and Emotional Assessment, Mini-SEA), and behavioral assessments (Frontal Behavioral Inventory, FBI; Interpersonal Reactivity Index-Emphatic Concern, IRI-EC; IRI-Perspective Taking, IRI-PT; and Self-Monitoring Scale-revised version, r-SMS). Receiver operating characteristic (ROC) analysis to calculate the area under the curve (AUC) was performed to compare the brief screening tests individually and combined to the gold standard of bvFTD and AD diagnoses. Results: The AD group was significantly older than the bvFTD group (p < 0.001). An analysis of the discriminatory ability of the ACE-III to distinguish between patients with AD and bvFTD (AUC = 0.85) and the INECO Frontal Screening (IFS; AUC = 0.78) shows that the former has greater discriminatory ability. Social and behavioral cognition tasks were able to appropriately discriminate bvFTD from AD. The Mini-SEA had high sensitivity and high moderate specificity (83%) for discriminating bvFTD from AD, which increased when combined with the brief screening tests ACE-III and IFS. The FBI was ideal with high sensitivity (83%), as well as the IRI-EC and IRI-PT that also were adequate for distinguishing bvFTD from AD. Conclusions: Our study supports the integration of socio-behavioral measures to the standard global cognitive and social cognition measures utilized for screening for bvFTD in a population with low levels of education.

Thyroid Dysfunction, Vitamin B12, and Folic Acid Deficiencies Are Not Associated With Cognitive Impairment in Older Adults in Lima, Peru.

Background: Reversible etiologies of cognitive impairment are common and treatable, yet the majority of mild cognitive impairment (MCI) and dementia research in Latin America has focused on irreversible, neurodegenerative etiologies. Objective: We sought to determine if thyroid dysfunction and vitamin B12 and folate deficiencies are associated with cognitive disorders among older adults with memory complaints in Lima, Peru. Methods: This was a retrospective review of patients who presented for cognitive evaluations to a multidisciplinary neurology clinic in Lima, Peru from January 2014 to February 2020. We included individuals aged ≥60 years, native Spanish-speakers, with at least a primary school educational level and a complete clinical assessment. Patients had either subjective cognitive decline (SCD), MCI, or dementia. One-way ANOVA and multiple logistic regression analyses were performed. Results: We included 720 patients (330 SCD, 154 MCI, and 236 dementia); the dementia group was significantly older [mean age SCD 69.7 ± 4.1, dementia 72.4 ± 3.7 (p = 0.000)] and had lower folate levels than SCD patients. The MCI group had higher free T3 levels compared with SCD patients. Those with lower TSH had greater dementia risk (OR = 2.91, 95%CI: 1.15-6.86) but not MCI risk in unadjusted models. B12 deficiency or borderline B12 deficiency was present in 34% of the dementia group, yet no clear correlation was seen between neuropsychological test results and B12 levels in our study. There was no association between MCI or dementia and thyroid hormone, B12 nor folate levels in adjusted models. Conclusion: Our findings do not support an association between metabolic and endocrine disorders and cognitive impairment in older Peruvians from Lima despite a high prevalence of B12 deficiency. Future work may determine if cognitive decline is associated with metabolic or endocrine changes in Latin America.

Neuropsychiatric Symptoms in Patients With Alzheimer's Disease During SARS-COV-2 Pandemic in Peru.

To evaluate neuropsychiatric symptoms in patients with Alzheimer's disease (AD) and their association with cognition and functionality during lockdown of the COVID-19's first wave. We included 91 patients and caregivers of people with AD from a memory clinic. The RUDAS, M@T, and CDR were administered to patients and NPI/ADCS-ADL to caregivers. Baseline and lockdown measurements scales were analyzed to compare the frequencies at baseline versus lockdown and conditional Odds Ratio (ORc) was calculated for the neuropsychiatric symptoms. During the pandemic, significant increase in the number of cases was observed in depression (23%), agitation (36.8%), aberrant motor activity (12%), sleep disorders (26.3%), and appetite change (12.1%). In worsening of pre-existing symptoms, the most frequent were delusions (75%), followed by sleep disorders (71.7%). Lockdown induces a rapid increase of neuropsychiatric symptoms affecting cognitive symptoms and functionality of Peruvian patients with AD.

Performance of the Rowland Universal Dementia Assessment Scale for the Detection of Mild Cognitive Impairment and Dementia in a Diverse Cohort of Illiterate Persons From Rural Communities in Peru.

Background: The accurate diagnosis of neurocognitive disorders in illiterate Peruvian populations is challenging, largely owing to scarcity of brief cognitive screening tools (BCST) validated in these diverse populations. The Peruvian version of the Rowland Universal Dementia Assessment Scale (RUDAS-PE) is a BCST that relies minimally on educational attainment and has shown good diagnostic accuracy in an urban illiterate population in Peru, yet its psychometric properties in illiterate populations in rural settings of the country have not been previously investigated. Objectives: To establish the diagnostic accuracy of the RUDAS-PE compared to expert clinical diagnosis using the Clinical Dementia Rating (CDR) Scale in healthy and cognitively impaired illiterate persons living in two culturally and geographically distinct rural communities of Peru. Methods: A cross-sectional, population-based study of residents ≥ 50 years of age living in the Peruvian rural communities of Santa Clotilde and Chuquibambilla. A total of 129 subjects (76 from Santa Clotilde and 53 from Chuquibambilla) were included in this study. Gold standard diagnostic neurocognitive evaluation was based on expert neurological history and examination and administration of the CDR. Receiver operating characteristics, areas under the curve (AUC), and logistic regression analyses were conducted to determine the performance of RUDAS-PE compared to expert gold standard diagnosis. Results: Compared to gold standard diagnosis, the RUDAS-PE was better at correctly discriminating between MCI and dementia than discriminating between MCI and controls in both sites (97.0% vs. 76.2% correct classification in Chuquibambilla; 90.0% vs. 64.7% in Santa Clotilde). In Chuquibambilla, the area under the curve (AUC) of the RUDAS to discriminate between dementia and MCI was 99.4% (optimal cutoff at <18), whereas between MCI and controls it was 82.8% (optimal cutoff at <22). In Santa Clotilde, the area under the curve (AUC) of the RUDAS to discriminate between dementia and MCI was 99.1% (optimal cutoff at <17), whereas between MCI and controls it was 75.5% (optimal cutoff at <21). Conclusions: The RUDAS-PE has acceptable psychometric properties and performed well in its ability to discriminate MCI and dementia in two cohorts of illiterate older adults from two distinct rural Peruvian communities.

Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population.

Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. The apolipoprotein E (ApoE) ε4 is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic white populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation in ε4 risk is correlated with the genetic ancestral background local to the ApoE gene. Native American populations are substantially underrepresented in AD genetic studies. The Peruvian population with up to ~80 of Amerindian (AI) ancestry provides a unique opportunity to assess the role of AI ancestry in AD. In this study, we assess the effect of the ApoE ε4 allele on AD in the Peruvian population. A total of 79 AD cases and 128 unrelated cognitive healthy controls from Peruvian population were included in the study. Genome-wide genotyping was performed using the Illumina Global screening array v2.0. Global ancestry and local ancestry analyses were assessed. The effect of the ApoE ε4 allele on AD was tested using a logistic regression model by adjusting for age, gender, and population substructure (first 3 principal components). Results showed that the genetic ancestry surrounding the ApoE gene is predominantly AI (60.6%) and the ε4 allele is significantly associated with increased risk of AD in the Peruvian population (odds ratio = 5.02, confidence interval: 2.3-12.5, p-value = 2e-4). Our results showed that the risk for AD from ApoE ε4 in Peruvians is higher than we have observed in non-Hispanic white populations. Given the high admixture of AI ancestry in the Peruvian population, it suggests that the AI genetic ancestry local to the ApoE gene is contributing to a strong risk for AD in ε4 carriers. Our data also support the findings of an interaction between the genetic risk allele ApoE ε4 and the ancestral backgrounds located around the genomic region of ApoE gene.

Systematic Review of the Diagnostic Validity of Brief Cognitive Screenings for Early Dementia Detection in Spanish-Speaking Adults in Latin America.

Objectives: The aim of this study was to evaluate the validity of brief cognitive screening (BCS) tools designed to diagnose mild cognitive impairment (MCI) or dementia in Spanish-speaking individuals over the age of 50 years from Latin America (LA). Methods: A systematic search of titles and abstracts in Medline, Biomed Central, Embase, Scopus, Scirus, PsycINFO, LILACS, and SciELO was conducted. Inclusion criteria were papers written in English or Spanish involving samples from Spanish-speaking Latin American individuals published until 2018. Standard procedures were applied for reviewing the literature. The data related to the study sample, methodology, and procedures applied, as well as the performance obtained with the corresponding BCS, were collected and systematized. Results: Thirteen of 211 articles met the inclusion criteria. The studies primarily involved memory clinic-based samples, with the exception of two studies from an adult day-care center, one from a primary care clinic, and one from a community-based sample. All the studies originated from five of the 20 countries of LA and all used standardized diagnostic criteria for the diagnosis of dementia and MCI; however, the diagnostic protocols applied differed. Most studies reported samples with an average of 10 years of education and only one reported a sample with an average of <5 years of education. No publication to date has included an illiterate population. Although the Montreal cognitive assessment (MoCA) is the most widely-used BCS tool in LA, it is significantly influenced by education level. Conclusions: Although evidence is still limited, the findings from studies on LA populations suggest that MoCA requires cultural adaptations and different cutoff points according to education level. Moreover, the diagnostic validity of the INECO frontal screening (IFS) test should be evaluated in populations with a low level of education. Given the heterogeneity that exists in the levels of education in LA, more studies involving illiterate and indigenous populations are required.

Depression in women with a diagnosis of breast cancer. Prevalence of symptoms of depression in Peruvian women with early breast cancer and related sociodemographic factors.

We sought to review literature on the prevalence of symptoms of depression in women with a diagnosis of breast cancer (BC) and in the Peruvian population determine the prevalence of symptoms of depression and to describe the association with sociodemographic characteristics. Descriptive cross-sectional analytical study of 254 patients from the National Cancer Institute of Peru (Instituto Nacional de Enfermedades Neoplásicas) with a diagnosis of clinical stage I or II BC. The patients included women aged between 26 and 67 years old. Symptoms of depression were monitored by the Beck Depression Inventory-II. Moreover, clinical features and patient sociodemographic characteristics were analyzed and their association with depression was assessed by logistic regression. The average age of the patients was 47.8 ± 9.2 years; 5.4% of the patients were postmenopausal at the time of the questionnaire. About 55% of women were from Lima, 58.3% had completed secondary education (11 ± 3.2 years), 45.7% were not working, and 46.5% were single. The prevalence of depression was 25.6% at the time of BC diagnosis. Of those patients with symptoms of depression, 16.9% showed symptoms of mild depression, 6.3% moderate, and 2.4% severe. A multivariable logistic regression model showed that in Peruvian women with a diagnosis of BC being married or employed significantly decreased the odds of presenting depressive symptoms (P = 0.029 and 0.017, respectively). Our main limitation was the lack of evaluation of depressive symptoms before the diagnosis, during or at the end of treatment. Another limitation was that the Beck Depression Inventory-II test could only identify depressive symptoms, but not depression as a disease. We have reviewed relevant literature on depression in women with a diagnosis of BC. The data presented suggests an association between both employment and marital status with depressive symptoms among Peruvian women with a diagnosis of BC. Pre-emptive support for women at risk could influence resilience and/or motivation for compliance with antineoplastic treatments.