Ricardo Nitrini

Background LatAm‐FINGERS is a non‐pharmacological multicenter randomized clinical trial aimed at preventing cognitive impairment. The intervention advocates for a lifestyle change based on diet, exercise, risk factor control, cognitive training, and socialization. However, the baseline assessment lacks a evaluation of the participants sociability b...

Background LatAm‐FINGERS is the first non‐pharmacological multicenter randomized clinical trial aimed at preventing cognitive impairment in Latin America. It encompasses twelve countries that collectively represent 45% of the territory in the Americas. Its objective is to reach populations that, despite sharing commonalities such as language, are c...

Background LatAm‐FINGERS ‐ the first non‐pharmacological multicenter randomized clinical trial in Latin America ‐ is a valuable opportunity to study lifestyle in a heterogeneous and multiethnic population exposed to a large number of cardiovascular risk factors. Our aims are to study the risk distribution in the LatAm‐FINGERS cohort and to explore...

Background The LatAm‐FINGERS trial marks a pioneering initiative as the first non‐pharmacological clinical trial encompassing participants from 12 Latin American countries, including Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Ecuador, Dominican Republic, Mexico, Peru, Puerto Rico, and Uruguay. This initiative represents a significant...

Cognitive impairment and symptoms of psychiatric disorders have been reported frequently as features of post‐acute sequelae of SARS‐CoV‐2 infection. This study aims to investigate subjective memory complaints in COVID‐19 survivors and determine if these are more strongly associated with objective cognitive impairment related to sequelae of SARS‐CoV...

Background Cognitive impairment is very common in stroke patients and is rarely diagnosed. Cognitive deficits involving language functions, praxis, visuospatial, visuoconstructive skills and memory are prominent. The available cognitive assessment tests do not address some specific characteristics of stroke patients and have important limitations i...

Background The Neuromodulatory Subcortical System (NSS) consists of nuclei exhibiting early vulnerability to tauopathies, including Alzheimer’s Disease (AD). Within the NSS, there is a spectrum of vulnerability that becomes apparent in the earliest stages of AD, offering a chance to probe factors underlying vulnerability to AD. Method In this stud...

Background Racial differences in dementia prevalence and incidence were found with higher dementia burden in African descendants. Previous neuropathological studies were conducted mostly in white participants in convenience samples. Further studies in diverse populations are important to foster the understanding of race differences in dementia path...

Background Hypertension is a midlife modifiable risk factor for dementia. Uncontrolled hypertension is related to brain damage that could result in cognitive impairment, and one way of evaluating uncontrolled hypertension through life is assessing left ventricular hypertrophy (LVH). Previous imaging studies have shown a relationship between LVH and...

Background Cardiovascular risk factors (CVRF) are among the main modifiable risk factors for dementia in Latin America (LA). Therefore, improving cardiovascular health (CVH) is one of the main objectives of the LatAm‐FINGERS trial, the largest non‐pharmacological (lifestyle improvement) randomized trial in LA. But, to fully comprehend CVH it is nec...

Background Despite the increasing number of people with dementia, it remains underdetected worldwide, even in high‐income countries. In Brazil, the number of people with dementia is expected to triple by 2050 and diagnosis can be challenging, contributing to high and growing rates of underdiagnosis. At the moment, there is no national estimate of u...

Background Some older adults with subjective decline (SCD) had a positive amyloid biomarker indicating a preclinical stage of Alzheimer’s disease. Objectives To assess the accuracy of Delayed Recall of Figure Memory Test (DR‐FMT) of Brief Cognitive Screening Battery to predict amyloid status in SCD older adults. Method The sample consisted of 45...

Background ApoE has been linked to individual differences in risk and resilience to neurodegeneration in normal aging. The ApoE4 genotype has been associated with an increased risk of developing late‐onset Alzheimer’s disease (age 65 and older). Within the cognitively healthy population, important differences have been reported in the distribution...

Background Nitric oxide (NO) is involved in synaptic transmission and cerebral plasticity, playing a role in the memory process. However, in states of brain inflammation, hypoxia, or ischemia, there is induction of inducible nitric oxide synthase (iNOS) expression by astrocytes and pyramidal cells in the brain. Under conditions of chronic activatio...

Background Previous studies suggest an association between Alzheimer’s disease and carotid artery atherosclerosis. However, the association between atherosclerotic carotid plaque composition and Alzheimer’s disease pathology (neuritic plaques and neurofibrillary tangles) has not been explored yet. Method Carotid arteries were dissected and the seg...

Background Transactive DNA‐binding protein 43 (TDP‐43) proteinopathy is associated with neurodegeneration, including LATE and linked to cognitive deterioration. While some research suggests a higher prevalence of TDP‐43 in women, no differences have been identified among racial groups. Nonetheless, the influence of gender on cognition within the co...

Background The atherosclerotic plaque in carotid arteries has been associated with dementia. Clinic radiological studies in older adults suggest that the composition of atherosclerotic plaque in the carotid artery can predict vascular dementia (VD) or mixed dementia. The proposed study aims to assess components of atherosclerotic plaques in the car...

Background The study of dementia and its differences between the sexes is widely investigated, mainly in Alzheimer’s disease. However, most studies on dementia are not carried out in a multiethnic population. Here we analyze demographic data, clinical symptoms, and neuropathological characteristics of a large mixed Brazilian sample. Method The Bio...

Background Prior research investigating sex and racial differences in amyloid pathology burden has yielded inconsistent findings. We examined the impact of sex and other confounding factors on neuritic plaque burden and cognitive outcomes. Method This study included 1,857 individuals, with post‐mortem brain tissues, from the Biobank for Aging Stud...

Background Clinicopathological studies suggest a role of minor cerebrovascular changes in the cognitive decline of individuals with a low neurodegenerative burden. However, it remains unclear whether small vascular brain lesions can impact cognition in middle aging individuals. Additionally, recent clinicopathological studies have shown that even a...

Objectives: Despite the increasing number of people with dementia (PWD), detection remains low worldwide. In Brazil, PWD is expected to triple by 2050, and diagnosis can be challenging, contributing to high and growing rates of underdiagnosis. At the moment, there is no national estimate of the under detection or characteristics of its distribution...

Background Antihypertensives (AHD) can influence cerebral autoregulation (CA) and attenuate hypertrophic concentric remodelling of arterioles. The aim of this study was to examine the associations between AHD, CA and structural and functional properties of cerebral arteries. Methods In this observational, cross‐sectional study 115 volunteers were...

Based on my work as a clinical neurologist with more than 50 years of experience in caring for patients with Alzheimer's disease (AD), I focus, in this review article, on the disease's two fundamental aspects for the doctor: diagnosis and treatment. The 1984 diagnostic criteria had been stable for more than a quarter of a century when it was replac...

In recent years, the diagnostic accuracy of Alzheimer’s disease has been enhanced by the development of different types of biomarkers that indicate the presence of neuropathological processes. In addition to improving patient selection for clinical trials, biomarkers can assess the effects of new treatments on pathological processes. However, there...

Novel therapies for Alzheimer’s disease, particularly anti-amyloid drugs like lecanemab and donanemab, have shown modest clinical benefits but also significant risks. The present paper highlights the challenges of access to diagnosis, cost-effectiveness, safety, and the need for more representation of diverse populations in clinical trials. Recomme...

Importance Since 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by soc...

Cognitive impairment and symptoms of psychiatric disorders have been reported frequently as features of post-acute sequelae of SARS-CoV-2 infection. This study aims to investigate subjective memory complaints in COVID-19 survivors and determine if these are more strongly associated with objective cognitive impairment related to sequelae of SARS-CoV...

Antihypertensive treatment (AT) is essential for preventing hypertension-related cognitive decline. The goals of this observational study were to compare cognitive performance (CP) between non-hypertensive (NH) volunteers and hypertensive patients and to evaluate the correlation between CP and antihypertensive drugs (AHD). Three groups were constit...

Background Age is the most important risk factor for develop dementia, and the recommendation is that older adults are cognitively tested to detect impairment in the initial stage for adequate treatment. The demand for the care of these older adults is great, drawing attention to the need for rapid tests, with good accuracy and simple application t...

Importance Race differences in dementia prevalence and incidence have previously been reported, with higher dementia burden in Black decedents. However, previous neuropathological studies were conducted mostly in convenience samples with White participants; conducting clinicopathological studies across populations is crucial for understanding the u...

Objectives Pathogenic variants in presenilin 1 (PSEN1) are related to early-onset Alzheimer disease (AD) and may occur as de novo variants. In comparison with sporadic forms, it can present with psychiatric manifestations, seizures, myoclonus, and focal presentation. Because PSEN1 can occur in young patients who lack a family history of neurologic...

Background: The Addenbrooke’s Cognitive Examination-Revised (ACE-R) is an accessible cognitive tool that supports the early detection of mild cognitive impairment (MCI), Alzheimer’s disease (AD), and behavioral variant frontotemporal dementia (bvFTD). Objective: To investigate the diagnostic efficacy of the ACE-R in MCI, AD, and bvFTD through the i...

Superagers, older adults with memory performance similar to middle-aged individuals, were studied to identify key neural networks responsible for their brain function connectivity. Using a previously published resting-state fMRI (rs-fMRI) dataset from 31 participants (14 superagers and 17 controls) examined at 3 and 7 Tesla (T) scanners, we cross-v...

The absence of a natural animal model is one of the main challenges in Alzheimer’s disease research. Despite the challenges of using nonhuman primates in studies, these animals can bridge mouse models and humans, as nonhuman primates are phylogenetically closer to humans and can spontaneously develop AD-type pathology. The capuchin monkey, a New Wo...

In recent years, we have seen a significant increase in the incidence and prevalence of oncological diseases. With the evolution of treatments and the tendency to increase the life expectancy of cancer patients, it is necessary to consider even more: not only survival but also the quality of life in this period, with the individual being able to ma...

Background Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer’s disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to e...

Background Corticobasal syndrome (CBS) is associated with diverse underlying pathologies, including the four‐repeat (4R)‐tauopathies. The Movement Disorders Society (MDS) criteria for progressive supranuclear palsy (PSP) proposed the novel category “probable 4R‐tauopathy” to address the phenotypic overlap between PSP and corticobasal degeneration (...

Introduction Arterial hypertrophy and remodeling are adaptive responses present in systemic arterial hypertension that can result in silent ischemia and neurodegeneration, compromising brain connections and cognitive performance (CP). However, CP is affected differently over time, so traditional screening methods may become less sensitive in assess...

The absence of a natural animal model is one of the main challenges in Alzheimer’s disease research. Despite the challenges of using non-human primates in studies, they can bridge mouse models and humans, as non-human primates are phylogenetically close to humans and can spontaneously develop AD-type pathology. The capuchin monkey, a New World prim...

Introduction The Brazilian population in the United States (U.S.), a Latinx subgroup, is rapidly growing and aging but remains underrepresented in U.S. health research. In addition to group‐specific genetic and environmental risks, Brazilian immigrants and their offspring in the U.S. likely have cumulative risks for health inequities. It is estimat...

Background: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are important causes of dementia with challenging differential diagnoses in many cases. Addenbrooke's Cognitive Examination-Revised (ACE-R) is a cognitive battery that may be useful to differentiate the two disorders. Objective: The objectibe of this stud...

Introduction: Apolipoprotein E (APOE) ε4 allele has been associated with higher carotid atherosclerosis risk, while the APOE-ε2 seems to decrease this risk. Data from autopsy studies, where carotid arteries can be evaluated in their full extension, is scarce. Therefore, we investigated the association between APOE alleles and direct morphometric m...

Background Frontotemporal dementia (FTD) is a frequent cause of young-onset dementia and represents a major challenge for the diagnosis and clinical management. It is essential to evaluate the difficulties faced by physicians on the diagnostic workup and on patient care. Objective The aim of this study was to investigate the current practices and t...

Alzheimer’s disease (AD) represents a substantial burden to patients, their caregivers, health systems, and society in Latin America and the Caribbean (LAC). This impact is exacerbated by limited access to diagnosis, specialized care, and therapies for AD within and among nations. The region has varied geographic, ethnic, cultural, and economic con...

Background Corticobasal syndrome (CBS) is a neurodegenerative disease related to multiple underlying pathologies, including four‐repeat (4R) tauopathies, namely corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), Alzheimer’s disease (AD), among others. The Movement Disorders Society‐PSP clinical criteria proposed a diagnostic...

Background Neuropsychiatric symptoms (NPS) are very common in Lewy body dementias (LBD), but their aetiology is poorly understood. In a post‐mortem study we aimed to characterise the contribution of neuropathological substrates to some of the most common NPS in dementia. Method Participants who passed away between 2004 and 2021 underwent comprehen...

Background The ACE‐R is an accurate and brief cognitive battery for the detection of mild dementia, especially for the discrimination between Alzheimer’s disease (AD) and frontotemporal dementia. The aim of this study was to develop a new logarithm based on discriminative items of the ACE‐R combined with relevant demographic characteristics that ma...

Background The COVID‐19 pandemic is accelerating the use of telemedicine in the management of chronic neurological diseases. However, studies on the feasibility of assessing language and cognition are still scarce, especially in developing countries in which education is very heterogeneous. This pilot study evaluated the feasibility of using teleme...

Bipolar disorder (BD) presents with a progressive course in a subset of patients. However, our knowledge of molecular changes in older BD is limited. In this study, we examined gene expression changes in the hippocampus of BD from the Biobank of Aging Studies to identify genes of interest that warrant further exploration. RNA was extracted from the...

Background Professional soccer athletes are exposed to repetitive head impacts and are at risk of developing chronic traumatic encephalopathy. Objective To evaluate regional brain glucose metabolism (rBGM) and gray matter (GM) volume in retired soccer players (RSPs). Methods Male RSPs and age and sex-matched controls prospectively enrolled between...

Unlabelled: Subjective cognitive decline is defined as a self-perceived cognitive decline but with normal performance in neuropsychological assessments. Objective: To verify the evolution of patients diagnosed with subjective cognitive decline compared to the cognitively normal group without any concern. Methods: This is a follow-up study base...

Objective To analyze the potential impact of sociodemographic, clinical and biological factors on the long-term cognitive outcome of patients who survived moderate and severe forms of COVID-19. Methods We assessed 710 adult participants (Mean age = 55 ± 14; 48.3% were female) 6 to 11 months after hospital discharge with a complete cognitive batter...

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....

The human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. W...

Introduction: Cognitive impairment is common after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, associations between post-hospital discharge risk factors and cognitive trajectories have not been explored. Methods: A total of 1105 adults (mean age ± SD 64.9 ± 9.9 years, 44% women, 63% White) with severe coronav...

Background: Education is believed to contribute positively to brain structure and function, as well as to cognitive reserve. One of the brain regions most impacted by education is the medial temporal lobe (MTL), a region that houses the hippocampus, which has an important role in learning processes and in consolidation of memories, and is also kno...

Arterial hypertrophy and remodeling are adaptive responses present in SAH that can result in silent ischemia and neurodegeneration, compromising brain connections and cognitive abilities. However, antihypertensives can minimize these histological changes. We try to assess whether cerebrovascular hemodynamic parameters, representative of these histo...

Dementia affects more Black individuals, likely due to a combination of environmental and biological factors1,2,3. APOE ε4 allele risk of dementia is different between individuals with European (EUR) and African (AFR) ancestries4,5,6. It is unclear what drives these differences in Alzheimer’s disease (AD) neuropathology among patients with cognitiv...

Background Most people with dementia already live in low‐ to middle‐income countries (LMIC). However, most evidence regarding dementia prevention comes from high‐income countries that have different socioeconomic status (SES) and risk factors prevalence than LMIC. In this session, we will present results on risk and protective factors for dementia...

The LatAm‐FINGERS initiative is a non‐pharmacological intervention trial to prevent cognitive impairment in 12 Latin American countries. Our aim is to describe the challenges faced when launching a multi‐country trial and the strategies used to tackle them. The principal challenges included: 1) Training personnel from the different teams in trial p...

More than 300 variants in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) genes have been reported to cause Dominantly Inherited Alzheimer Disease (DIAD). However, most of these reports come from non‐Hispanic whites and the full extent of DIAD remains understudied in Latin American (LatAm) countries. Here we descr...

The Latin American FINGERS initiative gathers 12 countries, including Spanish and Portuguese‐speaking populations. We aim to describe challenges and opportunities related to launching a multi‐country trial during the Covid‐19 pandemic. Identified challenges included. a) To train personnel from the different teams in trial procedures b) To assess th...

The aim of this study was to characterize the oral discourse of CBS patients and to verify whether measures obtained during a semi-spontaneous speech production could differentiate CBS patients from controls. A second goal was to compare the performance of patients with CBS probably due to Alzheimer’s disease (CBS-AD) pathology and CBS not related...

In the absence of clinically meaningful disease‐modifying treatments, the number of adults with dementia worldwide is projected to more than triple. Much of this increase will occur in low and middle‐income countries (LMICs); by 2050, 68% of adults living with dementia will be in LMICs. However, there is a gross under‐representation of LMICs in his...

In low‐ and middle‐income countries, the educational level of the population tends to vary significantly and persons with no literacy are in high numbers. In addition, countries with vast territories, such as Brazil, present significant differences in culture and language. These facts pose challenges for cognitive assessment. To this date, most cog...

Arterial hypertrophy and remodeling are adaptive responses present in the systemic arterial hypertension (SAH). As a result, antihypertensive drugs (AHD) begin to play an important role in controlling the cerebral blood flow. To evaluate the influence of AHD on cerebral hemodynamic parameters (CHP). Three groups of patients were compared: hypertens...

This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer’s disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, seco...

This paper presents the consensus of the Scientific Department of Cognitive Neurology and Aging from the Brazilian Academy of Neurology on the diagnostic criteria for Alzheimer’s disease (AD) in Brazil. The authors conducted a literature review regarding clinical and research criteria for AD diagnosis and proposed protocols for use at primary, seco...

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 prevalen...