miRNAs in cerebrospinal fluid associated with Alzheimer's disease: A systematic review and pathway analysis using a data mining and machine learning approach.

Alzheimer's disease (AD) is the most common type and accounts for 60%-70% of the reported cases of dementia. MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in gene expression regulation. Although the diagnosis of AD is primarily clinical, several miRNAs have been associated with AD and considered as potential markers for diagnosis and progression of AD. We sought to match AD-related miRNAs in cerebrospinal fluid (CSF) found in the GeoDataSets, evaluated by machine learning, with miRNAs listed in a systematic review, and a pathway analysis. Using machine learning approaches, we identified most differentially expressed miRNAs in Gene Expression Omnibus (GEO), which were validated by the systematic review, using the acronym PECO-Population (P): Patients with AD, Exposure (E): expression of miRNAs, Comparison (C): Healthy individuals, and Objective (O): miRNAs differentially expressed in CSF. Additionally, pathway enrichment analysis was performed to identify the main pathways involving at least four miRNAs selected. Four miRNAs were identified for differentiating between patients with and without AD in machine learning combined to systematic review, and followed the pathways analysis: miRNA-30a-3p, miRNA-193a-5p, miRNA-143-3p, miRNA-145-5p. The pathways epidermal growth factor, MAPK, TGF-beta and ATM-dependent DNA damage response, were regulated by these miRNAs, but only the MAPK pathway presented higher relevance after a randomic pathway analysis. These findings have the potential to assist in the development of diagnostic tests for AD using miRNAs as biomarkers, as well as provide understanding of the relationship between different pathophysiological mechanisms of AD.

Optimal cardiovascular health is associated with slower cognitive decline.

BACKGROUND: Life's Simple 7, a lifestyle and cardiovascular index associated with cognition, has been updated to Life's Essential 8 (LE8) to include sleep. LE8 has been related to cardiovascular outcomes but its association with cognition is unclear. METHODS: In this longitudinal analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), LE8 score was based on health behaviors (diet, physical activity, nicotine exposure, and sleep health) as well as health-related factors (body mass index, blood lipids, blood glucose, and blood pressure). Cognition was assessed in three waves, 4 years apart, using the Consortium to Establish a Registry for Alzheimer's Disease - Word List, semantic and phonemic verbal fluency, the Trail-Making Test B (TMT-B), and a global composite score. We used linear mixed-model analysis, inverse probability weighting, and interaction analysis. RESULTS: At baseline, the mean age of the study cohort was 51.4 ± 8.9 years, 56% were women, and 53% were White. Higher baseline LE8 scores were associated with slower decline in global cognition (ß = 0.001, 95% confidence interval [CI] 0.001, 0.002; p < 0.001), memory (ß = 0.001, 95% CI 0.000, 0.002; p = 0.013), verbal fluency (ß = 0.001, 95% CI 0.000, 0.002; p = 0.003), and TMT-B (ß = 0.004, 95% CI 0.003, 0.005; p < 0.001). This association was mainly driven by LE8 health factors, particularly blood glucose and blood pressure. Age, sex, and race were modifiers of the association between LE8 and global cognitive decline (p < 0.001), suggesting it was more pronounced in older, male, and Black participants. CONCLUSIONS: Higher baseline LE8 scores were associated with slower global and domain-specific cognitive decline during 8 years of follow-up, mainly due to health factors such as blood glucose and blood pressure. Sociodemographic factors were modifiers of this association.

Clinical profile and survival analysis of Alzheimer's disease patients in a Brazilian cohort.

OBJECTIVE: To investigate the clinical and epidemiological characteristics of a large sample of patients with dementia due to Alzheimer's disease (AD) who were followed up at a cognitive neurology outpatient clinic. METHODS: Retrospective, longitudinal, and descriptive design. We collected data from patients with dementia due to AD who visited the outpatient clinic of the SARAH Network of Rehabilitation Hospitals in Rio de Janeiro, Brazil, between May 2009 and June 2019. The evaluated characteristics included age of onset, sex, education, family history, comorbidities, time until diagnosis, and survival rates. RESULTS: Overall, 1434 patients were evaluated, 74% of whom were women, with a mean age at symptom onset of 72.7 years and 75.8 at diagnosis. A positive family history was reported in 602 patients, with a first-degree relative in 86.3% of them. Hypertension was the most prevalent comorbidity, affecting 61.2% of the sample, and 16.2% were classified as having early-onset AD. The mean survival rate for the sample population was 112.8 months (9.4 years). The sample population was positively affected by dyslipidaemia. CONCLUSIONS: This study presents a clinical and epidemiological analysis of a large and diverse group of patients with AD. The study confirms previous observations such as a higher prevalence of AD in women, low education among sufferers, and the presence of a family history. The study also found that comorbidities significantly affected patient survival and provides new data on the survival rates of patients with early and late AD in the Brazilian population.

Promoting diverse perspectives: Addressing health disparities related to Alzheimer's and all dementias.

Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well-resourced, non-Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's-related risk factors in those other groups. The Alzheimer's Association hosted a virtual conference on June 14-16, 2021, supported in part by the National Institute on Aging (R13 AG072859-01), focused on health disparities. The conference was held entirely online and consisted of 2 days of core programming and a day of focused meetings centered on American Indian and Alaska Natives and on LGBTQIA+ populations. Over 1300 registrants attended discussions focused on the structural and systemic inequities experienced across diverse groups, as well as ways to investigate and address these inequities.

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease.

BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10-5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Clinical and functional correlates of parkinsonism in a population-based sample of individuals aged 75 + : the Pietà study.

BACKGROUND: Parkinsonism is strongly associated with ageing, and many studies have suggested that parkinsonian signs may affect up to half of older adults and is associated with a wide range of adverse health outcomes. We compared clinical and functional characteristics of oldest-old community-dwelling individuals with parkinsonism (parkinsonian group [PG]) to individuals without parkinsonism (non-parkinsonian group [NPG]. METHODS: The Pietà study is a population-based study conducted in Caeté, southeast Brazil, involving 607 individuals aged 75 + years submitted to an extensive clinical evaluation. A subset of 65 PG individuals (61.5% women, median age of 82 years) was compared to 542 NPG individuals (64.8% women, median age of 80 years). RESULTS: PG individuals had significantly more functional impairment, clinical comorbidities (including number of falls, loss of bladder control and dysphagia) and major depression. Multivariate analysis revealed that older age, higher UPDRSm scores, lower category fluency test (animals/minute) and delayed recall memory scores were associated with PG. This group was also more cognitively impaired, with lower performance than NPG individuals in the Mini-Mental State Examination, category fluency test (animals/minute), clock drawing and in delayed recall (p < 0.001 for all tests). UPDRSm scores were the most contributing factor to cognition that independently explained variability in functionality of the entire sample. CONCLUSION: Individuals aged 75 + years with parkinsonism were significantly more clinically and functionally impaired in this population-based sample. Cognitive dysfunction explained most of the loss of functionality in these patients. UPDRS-m scores contributed independently to explain variability in functionality in the whole sample.

Efficacy of anti-amyloid-ß monoclonal antibody therapy in early Alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: Studies targeting amyloid-ß in patients with Alzheimer's disease (AD) have conflicting results and early initiation of therapy may yield better outcomes. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Clinicaltrials.gov for randomized trials comparing monoclonal antibodies (mAbs) with placebo in MCI or mild dementia due to AD. RESULTS: Nineteen studies comprising 15,275 patients were included. In patients with early AD, mAbs reduced the rate of decline, in both the Clinical Dementia Rating Scale, the sum of boxes (CDR-SB; MD -0.30; 95% CI -0.42,-0.19; p < 0.01), and the Alzheimer's Disease Assessment Scale, cognitive subscore (ADAS-cog; SMD -0.80; 95% CI -10.25,-0.35; p < 0.01). The results were similar between clinical stages for CDR-SB (MCI, MD -0.19; 95% CI -0.35,-0.03; p = 0.02; mild dementia, MD -0.45; 95% CI -0.65,-0.25; p < 0.01; subgroup differences, p = 0.13), as well as for ADAS-Cog (MCI, SMD -0.83; 95% CI -1.49,-0.17; p = 0.01; mild dementia, SMD -0.69; 95% CI -1.32 to -0.05; p = 0.03; subgroup differences, p = 0.47). The risk of amyloid-related imaging abnormalities (ARIA) was significantly higher in patients taking mAbs, including ARIA-edema (RR 7.7; 95% CI 4.60 to 13.00; p < 0.01), ARIA-hemorrhage (RR 1.8; 95% CI 1.22 to 2.59; p < 0.01), and symptomatic or serious ARIA (RR 14.1; 95% CI 7.30 to 27.14; p < 0.01). CONCLUSION: Anti-amyloid-ß mAbs attenuate cognitive and functional decline compared with placebo in early AD; whether the magnitude of this effect is clinically important remains uncertain, especially relative to the safety profile of these medications. Starting immunotherapy in patients with MCI was not significantly different than starting in the mild dementia stage. PROSPERO REGISTRY: CRD42023430698.

Risk factors for dementia in Brazil: Differences by region and race.

INTRODUCTION: Twelve risk factors (RFs) account for 40% of dementia cases worldwide. However, most data for population attributable fractions (PAFs) are from high-income countries (HIC). We estimated how much these RFs account for dementia cases in Brazil, stratifying estimates by race and socioeconomic level. METHODS: We calculated the prevalence and communalities of 12 RFs using 9412 Brazilian Longitudinal Study of Aging participants, then stratified according to self-reported race and country macro-regions. RESULTS: The overall weighted PAF was 48.2%. Less education had the largest PAF (7.7%), followed by hypertension (7.6%), and hearing loss (6.8%). PAF was 49.0% and 54.0% in the richest and poorest regions, respectively. PAFs were similar among White and Black individuals (47.8% and 47.2%, respectively) but the importance of the main RF varied by race. DISCUSSION: Brazil's potential for dementia prevention is higher than in HIC. Education, hypertension, and hearing loss should be priority targets.

Association between carotid intima-media thickness and cognitive decline differs by race.

INTRODUCTION: Common carotid intima-media thickness (cIMT) is a marker of subclinical atherosclerosis and is associated with cognitive decline. Although carotid atherosclerosis is more frequent in White than in Black participants, little is known whether race modifies the association between cIMT and cognitive decline. METHODS: In this longitudinal analysis of the ELSA-Brasil, we assessed cIMT using ultrasound and cognitive performance using different domain tests. We used linear mixed models, interaction analysis, and race stratified analyses. RESULTS: Baseline high IMT values were associated with memory (p < 0.001), verbal fluency (p < 0.001), TMT-B (p < 0.001)), and global cognitive decline (p < 0.001). Race was an effect modifier in the association between IMT and global cognitive decline (0.043), with stronger association in White (p < 0.001) than in Black (p = 0.009) participants. DISCUSSION: Baseline IMT was associated with global and domain-specific cognitive decline and race modified this relationship, with stronger associations in White participants. HIGHLIGHTS: Carotid intima-media thickness (cIMT) was associated with cognitive decline. cIMT and cognitive decline association was stronger in White than in Black participants. We used inverse probability weighting to address attrition bias.

Biomarkers for dementia in Latin American countries: Gaps and opportunities.

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.

Gaps in clinical research in frontotemporal dementia: A call for diversity and disparities-focused research.

Frontotemporal dementia (FTD) is one of the leading causes of dementia before age 65 and often manifests as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). FTD's exact clinical presentation varies by culture, language, education, social norms, and other socioeconomic factors; current research and clinical practice, however, is mainly based on studies conducted in North America and Western Europe. Changes in diagnostic criteria and procedures as well as new or adapted cognitive tests are likely needed to take into consideration global diversity. This perspective paper by two professional interest areas of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment examines how increasing global diversity impacts the clinical presentation, screening, assessment, and diagnosis of FTD and its treatment and care. It subsequently provides recommendations to address immediate needs to advance global FTD research and clinical practice.

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.

Effects of dabigatran versus warfarin on 2-year cognitive outcomes in old patients with atrial fibrillation: results from the GIRAF randomized clinical trial.

BACKGROUND: Observational studies support a role for oral anticoagulation to reduce the risk of dementia in atrial fibrillation patients, but conclusive data are lacking. Since dabigatran offers a more stable anticoagulation, we hypothesized it would reduce cognitive decline when compared to warfarin in old patients with atrial fibrillation. METHODS: The GIRAF trial was a 24-month, randomized, parallel-group, controlled, open-label, hypothesis generating trial. The trial was done in six centers including a geriatric care unit, secondary and tertiary care cardiology hospitals in São Paulo, Brazil. We included patients aged ≥ 70 years and CHA2DS2-VASc score > 1. The primary endpoint was the absolute difference in cognitive performance at 2 years. Patients were assigned 1:1 to take dabigatran (110 or 150 mg twice daily) or warfarin, controlled by INR and followed for 24 months. Patients were evaluated at baseline and at 2 years with a comprehensive and thorough cognitive evaluation protocol of tests for different cognitive domains including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Exam (MMSE), a composite neuropsychological test battery (NTB), and computer-generated tests (CGNT). RESULTS: Between 2014 and 2019, 5523 participants were screened and 200 were assigned to dabigatran (N = 99) or warfarin (N = 101) treatment. After adjustment for age, log of years of education, and raw baseline score, the difference between the mean change from baseline in the dabigatran group minus warfarin group was - 0.12 for MMSE (95% confidence interval [CI] - 0.88 to 0.63; P = 0.75), 0.05 (95% CI - 0.07 to 0.18; P = 0.40) for NTB, - 0.15 (95% CI - 0.30 to 0.01; P = 0.06) for CGNT, and - 0.96 (95% CI - 1.80 to 0.13; P = 0.02) for MoCA, with higher values suggesting less cognitive decline in the warfarin group. CONCLUSIONS: For elderly patients with atrial fibrillation, and without cognitive compromise at baseline that did not have stroke and were adequately treated with warfarin (TTR of 70%) or dabigatran for 2 years, there was no statistical difference at 5% significance level in any of the cognitive outcomes after adjusting for multiple comparisons. TRIAL REGISTRATION: Cognitive Impairment Related to Atrial Fibrillation Prevention Trial (GIRAF), NCT01994265 .

Sex differences in the association between alcohol intake and cognitive decline over 4 years in a middle-aged cohort: The Brazilian Longitudinal Study of Adult Health.

BACKGROUND AND PURPOSE: The association between alcohol intake and cognitive decline has been widely studied. Sex differences and cognitive domains affected by alcohol intake patterns make this topic complex. The objective of this study was to investigate the effect of alcohol intake on cognition in middle-aged participants in the Brazilian Longitudinal Study of Adult Health by sex during 4 years of follow-up. METHODS: A total of 7595 participants (55% women) aged between 50 and 75 years at baseline were assessed. Semantic and phonemic fluency, memory, and executive functions were assessed at baseline (2008-2010) and repeated during Visit 2. Linear mixed models were used to investigate the association between cognition and current abstainers, never drinkers, light drinkers, moderate drinkers, and heavy drinkers. RESULTS: Heavy alcohol intake accentuated the decline in executive functions for men (ß = -0.01, p < 0.05), and in semantic fluency (ß = -0.02, p < 0.05) and memory (ß = -0.02, p < 0.05) for women. Never drinker men also showed an accentuated decline in semantic fluency (ß = -0.02, p < 0.01). Moderate alcohol intake slowed cognitive decline in phonemic fluency for men (ß = 0.02, p < 0.01) and women (ß = 0.01, p < 0.01), and in executive functions (ß = 0.01, p < 0.05) for women. CONCLUSIONS: Having more than 14 drinks per week can impact executive functions in men and memory in women. In addition, alcohol consumption of seven to 14 drinks per week may have a protective effect on gender-specific cognitive functions. These findings should be considered in public health policies and guidelines on alcohol and cognitive aging.

Association Between Adherence to the MIND Diet and Cognitive Performance is Affected by Income: The ELSA-Brasil Study.

BACKGROUND: The relationship between the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diet and cognition has not been widely investigated in low- to middle-income countries. We investigated the relationship between MIND diet and cognition in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline data. METHODS: We included 11,788 participants. MIND diet adherence was based on the intake of 15 components according to a food frequency questionnaire. We analyzed the association between MIND diet adherence and global cognition, memory, and executive function using adjusted linear regression. We examined the interaction between income and MIND diet adherence on cognition and presented income stratified analyses. RESULTS: MIND diet adherence was not associated with cognition in the whole sample. Income was an effect modifier of MIND adherence on global cognition (P=0.03) and executive function (P<0.001). For participants with high income, greater adherence was associated with better executive function [ß=0.015, 95% confidence interval (CI)=0.002; 0.028, P=0.025]; while for participants with low income, greater adherence was associated with lower global cognition (ß=-0.020, 95% CI=-0.036; -0.005, P=0.010) and executive function (ß=-0.023, 95% CI=-0.039; -0.007, P=0.004). Adherence to the MIND diet was higher among participants with high income (P<0.001). CONCLUSION: For high-income participants, greater adherence was associated with better cognitive performance; for low-income participants, greater adherence was associated with lower cognitive performance.

Aphasia localization: was Pierre Marie right?

Language and its associated disorders have puzzled humanity since the dawn of civilization. The first descriptions of aphasia go back to classical antiquity. The Egyptians and Babylonians believed speech was a divine gift to mortals, and their descriptions of aphasia attributed these events to their Gods' anger and disfavour. The Edwin Smith Surgical Papyrus and the Hippocratic Corpus report several aphasia cases, relating this phenomenology to apoplexy, epilepsy, and other illnesses.

Episodic memory in progressive supranuclear palsy: a neuropsychological and neuroimaging study.

BACKGROUND: Episodic memory impairment may occur in progressive supranuclear palsy (PSP). However, it remains uncertain whether this is due to executive dysfunction or to the involvement of brain areas responsible for memory. OBJECTIVES: To investigate the specific brain regions underlying episodic memory impairment in PSP. METHODS: Twenty-one patients with PSP and 20 healthy controls underwent the Figure Memory Test (FMT) from the Brief Cognitive Screening Battery and brain MRI. We explored correlations between gray matter volumes and memory scores in PSP patients, adjusting for age and performance on the Frontal Assessment Battery. RESULTS: PSP patients performed worse than controls (p < 0.001) on delayed recall in the FMT. Delayed recall scores correlated to bilateral hippocampal and parahippocampal volumes in PSP patients. CONCLUSIONS: Medial temporal structures may play a role in episodic memory impairment in PSP, suggesting that amnesia in PSP is not solely due to executive dysfunction.

Slowly progressive behavioral frontotemporal dementia syndrome in a family co-segregating the C9orf72 expansion and a Synaptophysin mutation.

INTRODUCTION: Synaptophysin, already related to X-linked intellectual disability, is expressed mainly in the central nervous system. Studies in humans indicate that the downregulation of synaptophysin could be involved in the development of dementia. Our study presents the first familial case of behavioral variant frontotemporal dementia associated with the co-occurrence of the repeat expansion in C9orf72 and a pathogenic variant in the SYP gene. METHODS: Exome sequencing and repeat-primed PCR for C9orf72 were performed for two siblings with clinical and imaging findings suggestive of slowly progressive behavioral frontotemporal dementia. RESULTS: We found that both siblings have the hexanucleotide expansion in C9orf72 and a null variant in the SYP gene. The most affected sibling presents the putative variant in a hemizygous state. With milder symptoms, his sister has the same pathogenic variant in heterozygosis, compatible with X-linked inheritance. DISCUSSION: Our results strengthened previous suggestive evidence that the phenotypes associated with C9orf72 repeat expansion are variable and probably influenced by additional genetic modifiers. We hypothesized that the pathogenic variant in the SYP gene might have modified the typical phenotype associated with the C9orf72 mutation.

Alzheimer's disease and type 2 diabetes mellitus: A systematic review of proteomic studies.

Similar to dementia, the risk for developing type 2 diabetes mellitus (T2DM) increases with age, and T2DM also increases the risk for dementia, particularly Alzheimer's disease (AD). Although T2DM is primarily a peripheral disorder and AD is a central nervous system disease, both share some common features as they are chronic and complex diseases, and both show involvement of oxidative stress and inflammation in their progression. These characteristics suggest that T2DM may be associated with AD, which gave rise to a new term, type 3 diabetes (T3DM). In this study, we searched for matching peripheral proteomic biomarkers of AD and T2DM based in a systematic review of the available literature. We identified 17 common biomarkers that were differentially expressed in both patients with AD or T2DM when compared with healthy controls. These biomarkers could provide a useful workflow for screening T2DM patients at risk to develop AD.

Normative Data for the ELSA-Brasil Neuropsychological Assessment and Operationalized Criterion for Cognitive Impairment for Middle-Aged and Older Adults.

OBJECTIVES: Normative data should consider sociodemographic diversity for the accurate diagnosis of cognitive impairment. This study aims to provide normative data for a brief neuropsychological battery and present diagnostic criteria for cognitive impairment that could be used in primary care settings. METHODS: We selected 9618 Brazilian middle-aged and older adults after detailed exclusion criteria to avoid subtle cognitive impairment. We analyzed age, sex, and education influence on cognitive performance. To verify the evidence of criterion validity, we compared the cognitive performance of subjects with and without a depressive episode. Additionally, we verified the percentage of spurious scores under three different cutoffs. RESULTS: Age and education had the greatest impact on cognition. Normative scores were provided according to age and education groups. Participants with a depressive episode performed poorer than control subjects. The clinical cutoff of at least two scores below the 7th percentile revealed the adequate percentage of spurious and possible clinical performance. CONCLUSIONS: The Longitudinal Study on Adult Health (ELSA-Brasil) provided normative data based on a unique selected set of cognitively normal subjects. Normative groups were selected based on age and education, and the battery was sensitive to the presence of a depressive episode. We suggested clinical cutoffs for the tests in this battery that could be used in primary care settings to improve the accurate diagnosis of cognitive impairment.