Publications by authors named "Ricardo Allegri"

135 Publications

Accelerated epigenetic aging in adults with Down Syndrome in the Argentine population.

Alzheimers Dement 2021 Dec;17 Suppl 2:e058593

Fleni, Buenos Aires, Argentina.

Background: Life expectancy of individuals with Down Syndrome (DS) is currently 60 years. From age 40 they have an increased risk of dementia and almost all of them have histopathological features of Alzheimer's disease (AD) in their brains. Also, it is known that the ε4 allele of the APOE gene and the R47H variant of TREM2 increase the risk of AD. DS is also associated with a group of clinical manifestations of accelerated aging. DNA methylation-based biomarkers of ageing (epigenetic clocks) can be assessed by different models. It is known that DNA methylation age (DNAm) has a positive correlation with chronological age in disomic individuals while DS subjects exhibit an age acceleration effect in blood and brain.

Method: We determined the DNAm age of a cohort of seven participants with chromosome 21 trisomy (confirmed by G-banding karyotyping). Median age was 49 years. Their cognitive status was assessed by clinical and neuropsychological evaluations. AD risk variants in APOE and TREM2 were analyzed by RFLP-PCR. DNAm age was assessed in peripheral blood leukocytes, using the Illumina 850K platform. We used the Horvath's epigenetic clock, based on the DNAm levels of 353 specific CpG sites.

Result: Five participants exhibited the ε3/ε3 genotype in APOE and two of them the ε3/ε4 genotype. We did not observe the R47H risk variant in TREM2 in this group. Five participants showed a significant biological age acceleration and one participant's DNAm age was similar to his chronological age. Of note, one participant showed a deceleration in the DNAm age. This participant also had multiple myeloma. It is known that the DNA methylation profile of multiple myeloma cells differs from normal plasma cells. On the other hand, we did not find a trend towards a greater presence of the risk allele ε4 or cognitive impairment in participants with a significant DNAm age acceleration.

Conclusion: The majority participants presented an acceleration in their biological age, but this fact was not correlated with a greater presence of the risk allele ε4 or cognitive impairment. This is the first dataset of DNA methylation ages of a cohort of people with Down Syndrome in Latin America.
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http://dx.doi.org/10.1002/alz.058593DOI Listing
December 2021

Acute and Subacute Clinical Markers After Sport-Related Concussion.

Neurology 2022 Jan;98(1 Supplement 1):S16

Objective: This study aimed to determine the association of a range of off-field symptoms reported by athletes retrospectively with on-field concussion signs and in-office symptoms among rugby union players.

Background: Players with sports concussion experience multiple symptoms. Understanding the association between these symptoms and clinical markers of concussion would facilitate a targeted approach to symptom assessment and treatment.

Design/methods: Cross-sectional study. We consecutively enrolled 92 adult rugby union players, within the first 72 hours after sport concussion. Ten symptoms assessed using a retrospective symptoms interview were examined for their association with observed concussion signs and post-concussion symptoms using the Post-Concussion Symptoms Scale (PCSS).

Results: Odds ratios revealed that athletes who was overtly symptomatic based on retrospective concussion interview at the time of the concussion were over 2.6 times more likely ( = 0.047) to have exhibited post-traumatic amnesia when compared with athletes who was asymptomatic. There were no differences between groups in terms of on-field loss of consciousness or confusion. Off-field symptoms reported by athlete were associated with symptoms reporting on the Beck Depression Inventory (OR 2.8; 95% CI 1.14-6.88), headache (OR 4.9; 95% CI 1.92-12.79), memory concerns (OR 3.15; 95% CI 1.06-9.34), pressure in head (OR 2.8; 95% CI 1.03-8.08), and visual disturbances (OR 3.9; 95% CI 1.05-14.50) within the first 72 hours after concussion.

Conclusions: Symptomatic concussed rugby athletes have increased odds for sustaining on-field concussion signs that can be observed by others and persistent symptoms within the first 72 hours after concussion. Information from the on-field and off-field assessment is essential in understanding the severity of sports concussion.
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http://dx.doi.org/10.1212/01.wnl.0000801884.93340.fdDOI Listing
January 2022

Assessment of Argentine Health Care Providers' Knowledge on Sports-Related Concussion: A Cross-sectional Study.

Neurology 2022 Jan;98(1 Supplement 1):S15

Objective: To assess the current experience, beliefs and knowledge of survey respondents in the diagnosis and management of sports-related concussion and their relationship to formal concussion training.

Background: Athletes who have had a concussion may be at risk of a wide range of short- or long-term complications. The experience with and knowledge about concussion may be the most important factors for an effective concussion management.

Design/methods: A cross-sectional survey was conducted in July and August 2020 all over Buenos Aires, Argentina among health care professionals involved in the training and care of the competitive or recreational athletes. The survey covered: (i) the socio-demographic characteristics; (ii) experience; (iii) beliefs; and (iv) assessment of knowledge on sports concussion.

Results: A total of 626 participants completed and returned the questionnaire (response rate 86%). The majority of the health care professionals were physicians (n = 429; 68.5%). Nearly two-thirds (72%) of the respondents were related to rugby. Soccer was the second sport (6.2%). Seventy 4 percent of the respondents (n = 463) reported having concussion training. Respondents correctly answered on average 6.23 ± 2.16 (out of 10) concussion knowledge questions. The largest gaps were related to the topics of clinical interpretation of severity symptoms scales and neuroimaging. The smallest gaps were identified for young athletes (<18 years of age) management after a concussion. There was a significant difference in mean survey respondents' knowledge scores about concussion (F [1,622] = 109.479, < 0.001) between who had received the formal concussion training and those who had not, whilst adjusting for age and years the participant reported having had experience in sport.

Conclusions: Knowledge gaps exist in the clinical practice when dealing with professionals who are involved in the care of athletes. Our findings confirm the need for training and education on sport-related concussion.
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http://dx.doi.org/10.1212/01.wnl.0000801876.46061.a2DOI Listing
January 2022

Spanish version of the Frontotemporal Dementia Knowledge Scale: adaptation and validation.

Arq Neuropsiquiatr 2021 Dec 17. Epub 2021 Dec 17.

Fleni, Servicio de Neurología Cognitiva, Neuropsiquiatría y Neuropsicología, Departamento de Neurología, Buenos Aires, Argentina.

Background: Frontotemporal dementia (FTD) is a neurodegenerative disease and is one of the most common causes of dementia in people under 65. There is often a significant diagnostic delay, as FTD can be confused with other psychiatric conditions. A lack of knowledge regarding FTD by health professionals is one possible cause for this diagnostic confusion.

Objectives: The aim of this study was to adapt and validate the Frontotemporal Dementia Knowledge Scale (FTDKS) in Spanish.

Methods: A translation was done, following cross-cultural adaptation guidelines, which consisted of forward translation, blind back translation, and an analysis by a committee of experts. For the present study, 134 professionals from different health areas responded the Spanish version of the FTDKS. The statistical analysis was performed using R version 4.0.0 "Arbor day" and the Psych, sjPlot packages.

Results: The Spanish version of the FTDKS had good reliability and internal consistency (Cronbach alpha 0.74.). The sample's mean score was 19.78 (range = 4-32, SD 6.3) out of a maximum of 36 points.

Conclusions: The results obtained show that the Spanish version has good psychometric properties. The FTDKS is applicable in our environment and can be a useful tool to evaluate the knowledge of health professionals regarding frontotemporal dementia.
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http://dx.doi.org/10.1590/0004-282X-ANP-2020-0550DOI Listing
December 2021

Computational basis of decision-making impairment in multiple sclerosis.

Mult Scler 2021 Dec 21:13524585211059308. Epub 2021 Dec 21.

Department of Neurology, Fleni, Buenos Aires, Argentina.

Background: Multiple sclerosis (MS) is commonly associated with decision-making, neurocognitive impairments, and mood and motivational symptoms. However, their relationship may be obscured by traditional scoring methods.

Objectives: To study the computational basis underlying decision-making impairments in MS and their interaction with neurocognitive and neuropsychiatric measures.

Methods: Twenty-nine MS patients and 26 matched control subjects completed a computer version of the Iowa Gambling Task (IGT). Participants underwent neurocognitive evaluation using an expanded version of the Brief Repeatable Battery. Hierarchical Bayesian Analysis was used to estimate three established computational models to compare parameters between groups.

Results: Patients showed increased learning rate and reduced loss-aversion during decision-making relative to control subjects. These alterations were associated with: (1) reduced net gains in the IGT; (2) processing speed, executive functioning and memory impairments; and (3) higher levels of depression and current apathy.

Conclusion: Decision-making deficits in MS patients could be described by the interplay between latent computational processes, neurocognitive impairments, and mood/motivational symptoms.
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http://dx.doi.org/10.1177/13524585211059308DOI Listing
December 2021

Estimation of cognitive reserve and its impact on cognitive performance in older adults.

Appl Neuropsychol Adult 2021 Dec 6:1-11. Epub 2021 Dec 6.

Cognitive Neurology Service of the FLENI Foundation, Foundation for Childhood Neurological Disorders, Cognitive Neurology, Neuropsychology and Neuropsychiatry Section (CONICET-FLENI), Buenos Aires, Argentine.

Objectives: Cognitive reserve provides evidence in the search for answers regarding the role that lifestyle has in the protection of cognition in old age. Through a structural equations model, different things were analyzed: the relative weight of education, occupational complexity, free time activities and the intelligence quotient in cognitive reserve; and its impact on three cognitive domains: memory, language and executive functions.

Design: A trail analysis was executed, using structural equations procedure.

Participants: 167 older participants (mean = 76.74 years, standard deviation = 6.8 years).

Measurements: Participants were assessed with: Sociodemographic Questionnaire, Occupational Activity Agency Questionnaire, Social Participation Questionnaire and Neuropsychological Evaluation Battery for: memory, language and executive functions.

Results: The cognitive reserve factor is well represented by the measures included, with values ​​between .43 and .86, and shows a direct effect on language ( = .52,  < .001), executive functions ( = .77, <.001), and memory ( = .36,  = .003).

Conclusions: In conclusion, lifestyle factors, such as education, occupational complexity, leisure time activities and intelligence quotient have an impact on the conformation of cognitive reserve and performance in some psychological processes.
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http://dx.doi.org/10.1080/23279095.2021.2002864DOI Listing
December 2021

Editorial: Consequences of the COVID-19 Pandemic on Care for Neurological Conditions.

Front Neurol 2021 15;12:788912. Epub 2021 Nov 15.

Department of Cognitive Neurology, Neuropsychiatry and Neuropsychology, Instituto Neurológico Fleni, Buenos Aires, Argentina.

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http://dx.doi.org/10.3389/fneur.2021.788912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634886PMC
November 2021

Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease.

Alzheimers Dement 2021 Dec 2. Epub 2021 Dec 2.

Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.

As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and "sporadic" late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences.
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http://dx.doi.org/10.1002/alz.12505DOI Listing
December 2021

Cognitive consequences of COVID-19: results of a cohort study from South America.

Arq Neuropsiquiatr 2021 Nov 19. Epub 2021 Nov 19.

Fleni, Department of Cognitive Neurology, Buenos Aires, Argentina.

Background: Neurological and psychiatric manifestations associated with SARS-CoV-2 infection have been reported throughout the scientific literature. However, studies on post-COVID cognitive impairment in people with no previous cognitive complaint are scarce.

Objective: We aim to investigate the impact of COVID-19 on cognitive functions in adults without cognitive complaints before infection and to study cognitive dysfunction according to disease severity and cognitive risk factors.

Methods: Forty-five post-COVID-19 patients and forty-five controls underwent extensive neuropsychological evaluation, which assessed cognitive domains such as memory, language, attention, executive functions, and visuospatial skills, including psychiatric symptomatology scales. Data were collected on the severity of infection, premorbid medical conditions, and functionality for activities of daily living before and after COVID-19.

Results: Significant differences between groups were found in cognitive composites of memory (p=0.016, Cohen's d= 0.73), attention (p<0.001, Cohen's d=1.2), executive functions (p<0.001, Cohen's d=1.4), and language (p=0.002, Cohen's d=0.87). The change from premorbid to post-infection functioning was significantly different between severity groups (WHODAS, p=0.037). Self-reported anxiety was associated with the presence of cognitive dysfunction in COVID-19 subjects (p=0.043).

Conclusion: Our results suggest that the presence of cognitive symptoms in post-COVID-19 patients may persist for months after disease remission and argue for the inclusion of cognitive assessment as a protocolized stage of the post-COVID examination. Screening measures may not be sufficient to detect cognitive dysfunction in post-COVID-19 patients.
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http://dx.doi.org/10.1590/0004-282X-ANP-2021-0320DOI Listing
November 2021

Theory of mind, emotion recognition and emotional reactivity factors in early multiple sclerosis: Results from a South American cohort.

Appl Neuropsychol Adult 2021 Nov 22:1-11. Epub 2021 Nov 22.

Departamento de Neurología, FLENI, Buenos Aires, Argentina.

Objectives: To study different components of social cognition and quality of life in patients with early multiple sclerosis and low Expanded Disability Status Scale and to test the influence of cognitive performance, fatigue and neuropsychiatric symptoms on social cognition performance.

Methods: Thirty-four patients with relapsing-remitting MS, with ≤2 years of disease duration and scores ≤2 on the EDSS and 30 healthy controls underwent neuropsychological assessment with the Brief Repeatable Neuropsychological Test Battery. Components of social cognition, such as emotion recognition, theory of mind, empathy, and emotional reactivity, were assessed with the Reading the Mind in the Eyes test, the Faux Pas task, the International Affective Imagery System, and the Empathy Quotient. Anxiety, depression, fatigue and quality of life were measured.

Results: Patients showed significant differences in verbal memory, executive functions and social cognition, especially emotion recognition and ToM. Regarding emotional reactivity, patients showed a positive bias in the interpretation of the valence of neutral images.

Conclusions: Patients with early MS showed impairments in several components of social cognition independent of cognitive performance, neuropsychiatric symptoms and fatigue. Social cognition deficits may be present in MS even in the early stages.
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http://dx.doi.org/10.1080/23279095.2021.2004542DOI Listing
November 2021

Connectivity and Patterns of Regional Cerebral Blood Flow, Cerebral Glucose Uptake, and Aβ-Amyloid Deposition in Alzheimer's Disease (Early and Late-Onset) Compared to Normal Ageing.

Curr Alzheimer Res 2021 ;18(8):646-655

Centro de Imagenes Moleculares, Fleni. Ruta 9, km 52.5, B1625XAF Escobar, Buenos Aires, Argentina.

Purpose: The aim of this study was to investigate the differences in early (EOAD) and late (LOAD) onset of Alzheimer´s disease, as well as glucose uptake, regional cerebral blood flow (R1), amyloid depositions, and functional brain connectivity between normal young (YC) and Old Controls (OC).

Methodology: The study included 22 YC (37 ± 5 y), 22 OC (73 ± 5.9 y), 18 patients with EOAD (63 ± 9.5 y), and 18 with LOAD (70.6 ± 7.1 y). Patients underwent FDG and PIB PET/CT. R1 images were obtained from the compartmental analysis of the dynamic PIB acquisitions. Images were analyzed by a voxel-wise and a VOI-based approach. Functional connectivity was studied from the R1 and glucose uptake images.

Results: OC had a significant reduction of R1 and glucose uptake compared to YC, predominantly at the dorsolateral and mesial frontal cortex. EOAD and LOAD vs. OC showed a decreased R1 and glucose uptake at the posterior parietal cortex, precuneus, and posterior cingulum. EOAD vs. LOAD showed a reduction in glucose uptake and R1 at the occipital and parietal cortex and an increased at the mesial frontal and temporal cortex. There was a mild increase in an amyloid deposition at the frontal cortex in LOAD vs. EOAD. YC presented higher connectivity than OC in R1 but lower connectivity considering glucose uptake. Moreover, EOAD and LOAD showed a decreased connectivity compared to controls that were more pronounced in glucose uptake than R1.

Conclusion: Our results demonstrated differences in amyloid deposition and functional imaging between groups and a differential pattern of functional connectivity in R1 and glucose uptake in each clinical condition. These findings provide new insights into the pathophysiological processes of AD and may have an impact on patient diagnostic evaluation.
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http://dx.doi.org/10.2174/1567205018666211116095035DOI Listing
January 2021

[Spanish Norms for Mini-SEA (Mini Social Cognition and Emotional Assessment) in adults in Buenos Aires].

Vertex 2021 Jun;XXXII(152):5-10

Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría, Departamento de Neurología, FLENI, Buenos Aires, Argentina.

Introduction And Objective: The Mini-SEA is a quick and brief cognitive assessment test developed to study social cognition. It consists of a modified version of the faux pas Test and an emotional recognition test based on Ekman's faces. The objective of this work was to obtain the first Spanish Speaking norms for the Mini-SEA test.

Material And Methods: 64 healthy volunteers, between 35 and 80 years old, were recruited and evaluated with the Mini-SEA by specialized neuropsychologists from the Cities of Buenos Aires and La Plata, both in the Province of Buenos Aires, Argentina.

Results: The total mean (M) of the Mini-SEA was 25 +/- 4. The M of the faux pas Score was 12.5 +/- 2.4 and the M of the Emotional Recognition Score was 12.8 +/- 1.5. The sample was divided into 4 age groups: Group 1 (<50 years), Group 2 (50-59 years), Group 3 (60-69 years) and Group 4 (more than 70 years). Differences were found in the age continuum in the Emotional Recognition score between group 1 and 4 (p <0.05) and between group 3 and 4 (p <0.01), but not in the Faux Pas Score.

Conclusion: This study presents the first normative values of the Mini-SEA Social Cognition test for a Spanish-speaking population. The Mini-SEA, being a quick and easy to administer test, allows the study of social cognition in an adequate and precise way, especially in prodromal stages of neurodegenerative diseases.
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June 2021

Acute and post-acute neurological manifestations of COVID-19: present findings, critical appraisal, and future directions.

J Neurol 2021 Oct 21. Epub 2021 Oct 21.

Department of Neurology, Centre for Global Health, Technical University of Munich, Munich, Germany.

Acute and post-acute neurological symptoms, signs and diagnoses have been documented in an increasing number of patients infected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19). In this review, we aimed to summarize the current literature addressing neurological events following SARS-CoV-2 infection, discuss limitations in the existing literature and suggest future directions that would strengthen our understanding of the neurological sequelae of COVID-19. The presence of neurological manifestations (symptoms, signs or diagnoses) both at the onset or during SARS-CoV-2 infection is associated with a more severe disease, as demonstrated by a longer hospital stay, higher in-hospital death rate or the continued presence of sequelae at discharge. Although biological mechanisms have been postulated for these findings, evidence-based data are still lacking to clearly define the incidence, range of characteristics and outcomes of these manifestations, particularly in non-hospitalized patients. In addition, data from low- and middle-income countries are scarce, leading to uncertainties in the measure of neurological findings of COVID-19, with reference to geography, ethnicity, socio-cultural settings, and health care arrangements. As a consequence, at present a specific phenotype that would specify a post-COVID (or long-COVID) neurological syndrome has not yet been identified.
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http://dx.doi.org/10.1007/s00415-021-10848-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528941PMC
October 2021

Working Group Recommendations for the Practice of Teleneuropsychology in Latin America.

Arch Clin Neuropsychol 2021 Oct 20. Epub 2021 Oct 20.

Department of Cognitive Neurology, Fleni, Buenos Aires, Argentina.

Objective: Teleneuropsychology (teleNP) could potentially expand access to services for patients who are confined, have limited personal access to healthcare, or live in remote areas. The emergence of the COVID-19 pandemic has significantly increased the use of teleNP for cognitive assessments. The main objective of these recommendations is to identify which procedures can be potentially best adapted to the practice of teleNP in Latin America, and thereby facilitate professional decision-making in the region.

Method: Steps taken to develop these recommendations included (1) formation of an international working group with representatives from 12 Latin American countries; (2) assessment of rationale, scope, and objectives; (3) formulation of clinical questions; (4) evidence search and selection; (5) evaluation of existing evidence and summary; and (6) formulation of recommendations. Levels of evidence were graded following the Oxford Centre for Evidence-Based Medicine system. Databases examined included PubMed, WHO-IRIS, WHO and PAHO-IRIS, Índice Bibliográfico Español en Ciencias de la Salud (IBCS), and LILACS.

Results: Working group members reviewed 18,400 titles and 422 abstracts and identified 19 articles meeting the criteria for level of evidence, categorization, and elaboration of recommendations. The vast majority of the literature included teleNP tests in the English language. The working group proposed a series of recommendations that can be potentially best adapted to the practice of teleNP in Latin America.

Conclusions: There is currently sufficient evidence to support the use of videoconferencing technology for remote neuropsychological assessments. These recommendations will likely contribute to the advancement of teleNP research and practice in the region.
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http://dx.doi.org/10.1093/arclin/acab080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8574290PMC
October 2021

Changes in the Care of Neurological Diseases During the First Wave of the COVID-19 Pandemic: A Single Private Center Study in Argentina.

Front Neurol 2021 3;12:613838. Epub 2021 Sep 3.

Departamento de Neurología, Fleni, Buenos Aires, Argentina.

Healthcare systems are struggling to cope with the rapid evolution of the COVID-19 pandemic. In Argentina, the pandemic is advancing despite prolonged lockdown measures. We aim to analyze the impact of the easing of lockdown measures in the number of visits to the emergency department (ED), and outpatient consultations (OC) to a tertiary neurological center. We compared the number of ED visits with the social mobility overtime. We also compared the number of OC, and the geographic distribution of patients' addresses between 2019 and 2020. ED visits decreased 48.33% ( = 14,697 in 2019 vs. = 7,595 in 2020). At the beginning of the lockdown, the social mobility decreased in pharmacies/groceries, and workplaces, along with a reduction in the number of ED visits. With the easing of lockdown restrictions, the social mobility decreased in residential places, slightly increased in workplaces and almost return to normal in pharmacies/groceries. Variations in ED visits correlate better with social mobility in workplaces (coef. =0.75, < 0.001) than in groceries/pharmacies (coef. =0.68, < 0.001). OC decreased 43%. Fourteen percent of OC were tele consults. This was associated with an increase of the geographical area of influence of our center (standard distance of 109 km in 2019 and 127 km in 2020). Despite an increase in social mobility, the number of ED visits and OC to an Argentinian tertiary neurological center remain worrisomely low. The pandemic catalyzed the introduction of telemedicine in our country. This has also allowed patients from distant zones to gain access to specialized neurological care.
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http://dx.doi.org/10.3389/fneur.2021.613838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446505PMC
September 2021

What Do We Mean by Behavioral Disinhibition in Frontotemporal Dementia?

Front Neurol 2021 7;12:707799. Epub 2021 Jul 7.

Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CA, United States.

Behavioral variant frontotemporal dementia, unlike other forms of dementia, is primarily characterized by changes in behavior, personality, and language, with disinhibition being one of its core symptoms. However, because there is no single definition that captures the totality of behavioral symptoms observed in these patients, disinhibition is an umbrella term used to encompass socially disruptive or morally unacceptable behaviors that may arise from distinct neural etiologies. This paper aims to review the current knowledge about behavioral disinhibition in this syndrome, considering the cultural factors related to our perception of behavior, the importance of phenomenological interpretation, neuroanatomy, the brain networks involved and, finally, a new neuroscientific theory that offers a conceptual framework for understanding the diverse components of behavioral disinhibition in this neurodegenerative disorder.
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http://dx.doi.org/10.3389/fneur.2021.707799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292604PMC
July 2021

Comparison of CSF biomarkers in Down syndrome and autosomal dominant Alzheimer's disease: a cross-sectional study.

Lancet Neurol 2021 08;20(8):615-626

Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Background: Due to trisomy of chromosome 21 and the resultant extra copy of the amyloid precursor protein gene, nearly all adults with Down syndrome develop Alzheimer's disease pathology by the age of 40 years and are at high risk for dementia given their increased life expectancy compared with adults with Down syndrome in the past. We aimed to compare CSF biomarker patterns in Down syndrome with those of carriers of autosomal dominant Alzheimer's disease mutations to enhance our understanding of disease mechanisms in these two genetic groups at high risk for Alzheimer's disease.

Methods: We did a cross-sectional study using data from adults enrolled in the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study, a multisite longitudinal study of Alzheimer's disease in Down syndrome, as well as a cohort of carriers of autosomal dominant Alzheimer's disease mutations and non-carrier sibling controls enrolled in the Dominantly Inherited Alzheimer Network (DIAN) study. For ABC-DS, participants with baseline CSF, available clinical diagnosis, and apolipoprotein E genotype as of Jan 31, 2019, were included in the analysis. DIAN participants with baseline CSF, available clinical diagnosis, and apolipoprotein E genotype as of June 30, 2018, were evaluated as comparator groups. CSF samples obtained from adults with Down syndrome, similarly aged carriers of autosomal dominant Alzheimer's disease mutations, and non-carrier siblings (aged 30-61 years) were analysed for markers of amyloid β (Aβ, Aβ); tau phosphorylated at threonine 181-related processes; neuronal, axonal, or synaptic injury (total tau, visinin-like protein 1, neurofilament light chain [NfL], synaptosomal-associated protein 25); and astrogliosis and neuroinflammation (chitinase-3-like protein 1 [YKL-40]) via immunoassay. Biomarker concentrations were compared as a function of dementia status (asymptomatic or symptomatic), and linear regression was used to evaluate and compare the relationship between biomarker concentrations and age among groups.

Findings: We assessed CSF samples from 341 individuals (178 [52%] women, 163 [48%] men, aged 30-61 years). Participants were adults with Down syndrome (n=41), similarly aged carriers of autosomal dominant Alzheimer's disease mutations (n=192), and non-carrier siblings (n=108). Individuals with Down syndrome had patterns of Alzheimer's disease-related CSF biomarkers remarkably similar to carriers of autosomal dominant Alzheimer's disease mutations, including reductions (all p<0·0080) in Aβ to Aβ ratio and increases in markers of phosphorylated tau-related processes; neuronal, axonal, and synaptic injury (p<0·080); and astrogliosis and neuroinflammation, with greater degrees of abnormality in individuals with dementia. Differences included overall higher concentrations of Aβ and YKL-40 (both p<0·0008) in Down syndrome and potential elevations in CSF tau (p<0·010) and NfL (p<0·0001) in the asymptomatic stage (ie, no dementia symptoms).

Funding: National Institute on Aging, Eunice Kennedy Shriver National Institute of Child Health and Human Development, German Center for Neurodegenerative Diseases, and Japan Agency for Medical Research and Development.
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http://dx.doi.org/10.1016/S1474-4422(21)00139-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496347PMC
August 2021

Music Based Assessment for Cognitive Functions for Spanish-Speaking Adults With Acquired Brain Injury (ECMUS): A Pilot-Validation Study.

J Music Ther 2021 Nov;58(4):408-436

Rehabilitation Department, FLENI, Buenos Aires, Argentina.

Acquired brain injury (ABI) commonly causes cognitive dysfunction that needs to be assessed and treated to maximize rehabilitation outcomes. Research suggests that music, emotion, and cognition are intimately linked, and that music can contribute to the assessment and treatment of cognitive functions of adults who have suffered from ABI. To this date, no standardized music based assessment tool exists to identify and measure cognitive functioning and mood states of Spanish-speaking persons with ABI at treatment intake and over time. The objective of this study was to develop such a scale and determine its psychometric properties in terms of internal consistency, reliability, and concurrent validity. The "Evaluación de la Cognición Musical para Adultos con Lesión Cerebral Adquirida" (in English "Music Based Assessment for Cognitive Functions of Adults with Acquired Brain Injury - ECMUS") was developed and tested at a neurorehabilitation institute in Argentina. Twenty-four healthy adults and 20 adults with ABI were recruited and assessed with the ECMUS. Despite the limited number of participants, this preliminary psychometric examination shows promising results. The tool has an acceptable internal consistency, excellent test-retest and inter-rater reliability, and, depending on the subscale, weak to strong correlations to related, nonmusical constructs. Overall, this pilot study opens the possibility to further explore the inclusion of music in assessment procedures of Spanish-speaking individuals with ABI in rehabilitation settings. It is clinically derived and emphasizes evidence-based contributions of the field of music therapy to interdisciplinary assessment and treatment in rehabilitation settings.
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http://dx.doi.org/10.1093/jmt/thab011DOI Listing
November 2021

Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease.

Alzheimers Dement (Amst) 2021 5;13(1):e12197. Epub 2021 Jul 5.

The Florey Institute University of Melbourne Parkville Victoria Australia.

Introduction: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment.

Methods: We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally.

Results: Our risk score separated asymptomatic versus demented DIAD-MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%-98.2%]) and improved prediction beyond established methods based on familial age of onset.

Discussion: Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials.
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http://dx.doi.org/10.1002/dad2.12197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256623PMC
July 2021

Generation of a human induced pluripotent stem cell line from a familial Alzheimer's disease PSEN1 T119I patient.

Stem Cell Res 2021 05 5;53:102325. Epub 2021 Apr 5.

Laboratorios de Investigación Aplicada en Neurociencias (LIAN-CONICET), Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (Fleni), Escobar, Provincia de Buenos Aires, Argentina. Electronic address:

Human induced pluripotent stem cells (hiPSC) line FLENIi001-A was reprogrammed from dermal fibroblasts using the lentiviral-hSTEMCCA-loxP vector. Fibroblasts were obtained from a skin biopsy of a 72-year-old Caucasian male familial Alzheimer's disease patient carrying the T119I mutation in the PSEN1 gene. PSEN1 genotype was maintained and stemness and pluripotency confirmed in the FLENIi001-A hiPSC line.
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http://dx.doi.org/10.1016/j.scr.2021.102325DOI Listing
May 2021

Utility of a Spanish version of Three Words-Three Shapes Test to detect memory impairment in primary progressive aphasia.

Appl Neuropsychol Adult 2021 Apr 9:1-7. Epub 2021 Apr 9.

Ageing and Memory Clinic, FLENI, Buenos Aires, Argentina.

Introduction: Three Words-Three Shapes (3W3S) is a bedside test that assesses verbal and non-verbal memory and has proven useful in staging memory decline in amnestic disorders and primary progressive aphasia. Given its simple structure, the 3W3S can be easily adapted to other languages maintaining the original shapes and only modifying the words. We aim to validate a Spanish version of the 3W3S test and establish whether memory loss patterns present in amnesic disorders associated with Alzheimer's etiology and PPA were correctly characterized.

Method: The translation and adaptation of the 3W3S were performed according to standardized guidelines and applied to a cohort of patients with Dementia of Alzheimer's type (DAT = 20), mild cognitive impairment (aMCI= 20), primary progressive aphasia (PPA = 20), and healthy controls (HC = 20).

Results: In verbal memory performance, PPA patients' score was lower than that of MCI and HC and similar to DAT's in the effortless encoding ( < 0.001), delayed recall ( < 0.001), and recognition ( < 0.012). For non-verbal performance, PPA patients performed better than DAT and similar to HC and MCI subjects ( < 0.001).

Conclusions: Results show good applicability of 3W3S to determine memory function in PPA patients, independently from language ability. Visual and verbal components of memory are dissociated in PPA.
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http://dx.doi.org/10.1080/23279095.2021.1907391DOI Listing
April 2021

Impact of Social Isolation on People with Dementia and Their Family Caregivers.

J Alzheimers Dis 2021 ;81(2):607-617

Behavioral and Cognitive Research Group, Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brazil.

Background: People with dementia and their family caregivers may face a great burden through social isolation due to the COVID-19 pandemic, which can be manifested as various behavioral and clinical symptoms.

Objective: To investigate the impacts of social isolation due to the COVID-19 pandemic on individuals with dementia and their family caregivers.

Methods: Two semi-structured questionnaires were applied via telephone to family caregivers of people diagnosed with dementia in three cities in Argentina, Brazil, and Chile, in order to assess clinical and behavioral changes in people with dementia and in their caregivers.

Results: In general, 321 interviews were conducted. A significant decline in memory function has been reported among 53.0%of people with dementia. In addition, 31.2%of individuals with dementia felt sadder and 37.4%had increased anxiety symptoms. These symptoms of anxiety were greater in individuals with mild to moderate dementia, while symptoms of agitation were greater in individuals with severe dementia. Moreover, compulsive-obsessive behavior, hallucinations, increased forgetfulness, altered appetite, and increased difficulty in activities of daily living were reported more frequently among individuals with moderate to severe dementia. Caregivers reported feeling more tired and overwhelmed during this period and these symptoms were also influenced by the severity of dementia.

Conclusion: Social isolation during the COVID-19 pandemic triggered a series of negative behavioral repercussions, both for people with dementia and for their family caregivers in these three South American countries.
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http://dx.doi.org/10.3233/JAD-201580DOI Listing
June 2021

Diagnostic accuracy of the UDS 3.0 neuropsychological battery in a cohort with Alzheimer's disease in Colombia.

Appl Neuropsychol Adult 2021 Mar 24:1-9. Epub 2021 Mar 24.

Department of Psychology, Universidad de la Costa, Barranquilla, Colombia.

Background: Alzheimer's disease (AD) is a neurodegenerative disease that causes a gradual loss of cognitive functions and limits daily activities performance. Early diagnosis of AD is essential to start timely treatment. This study aimed to validate the Uniform Data Set neuropsychological battery version 3.0 (UDS 3.0) in a Colombian cohort.

Methods: This study is a cross-sectional type, consecutive, incidental, with 143 persons, divided into two groups: 48 diagnosed AD cases and 95 healthy controls, between the ages of 50 and 80+, and between 1 and 19+ years of education.

Results: The results indicate differences between the control group and the AD group in most battery tests. A significant correlation was found between the Montreal Cognitive Assessment (MoCA), Multilingual Naming Test (MINT), Craft Story, Benson Figure Test, P-word and F-word Phonemic Fluency Test, and their respective reference tests. Cutoff points were found based on the Youden index for each sub-test. The results indicate that all sub-tests are above the reference line of the ROC curve.

Conclusion: The use of the UDS 3.0 in Colombia would help improving clinical diagnostic routes because of its high accuracy and high correlation with tests that measure general impairment; it has good sensitivity and specificity, and it can be a useful tool for AD.
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http://dx.doi.org/10.1080/23279095.2021.1897007DOI Listing
March 2021

Segregation of functional networks is associated with cognitive resilience in Alzheimer's disease.

Brain 2021 08;144(7):2176-2185

Dementia Research Centre, University College London, Queen Square, London, UK.

Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer's disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal ageing, we tested the hypothesis that higher segregation of the brain's connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer's disease. Using resting-state functional MRI, we assessed both resting-state functional MRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: (i) 108 individuals with autosomal dominantly inherited Alzheimer's disease and 71 non-carrier controls; and (ii) 156 amyloid-PET-positive subjects across the spectrum of sporadic Alzheimer's disease and 184 amyloid-negative controls. In the autosomal dominant Alzheimer's disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer's sample, disease stage was assessed by temporal lobe tau-PET (i.e. composite across Braak stage I and III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer's disease, we found higher functional MRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (P = 0.007). Similarly, for patients with sporadic Alzheimer's disease, higher functional MRI-assessed system segregation was associated with less decrement in global cognition (P = 0.001) and episodic memory (P = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer's disease.
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http://dx.doi.org/10.1093/brain/awab112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370409PMC
August 2021

Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease.

Neurology 2021 03 25;96(12):e1632-e1645. Epub 2021 Jan 25.

From the Departments of Radiology (N.J.-M., T.M.B., B.A.G., G.C., P.M., R.C.H., T.L.S.B.), Neurology (E.M., J.H., B.M.A., R.J.P., J.C.M., R.J.B.), Psychological and Brain Sciences (J.H.), Psychiatry (C.C., C.M.K.), and Pathology and Immunology (R.J.P.) and Division of Biostatistics (G.W., C.X.), Washington University School of Medicine, St. Louis, MO; Banner Alzheimers Institute (Y.S.), Phoenix, AZ; Department of Cognitive Neurology and Neuropsychology (R.F.A.), Instituto de Investigaciones Neurológicas Fleni, Buenos Aires, Argentina; Departments of Neurology and Clinical and Translational Science (S.B.B.), University of Pittsburgh School of Medicine, PA; Department of Neurology (A.M.B.), Taub Institute for Research on Alzheimers Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY; Neuroscience Research Australia (W.S.B., P.R.S.); School of Medical Sciences (P.R.S.), University of New South Wales (W.S.B.), Sydney, Australia; Dementia Research Centre and UK Dementia Research Institute (D.M.C., N.C.F., A.O.), UCL Queen Square Institute of Neurology, London, UK; Departments of Neurology (J.P.C., K.A.J.) and Radiology (K.A.J.), Massachusetts General Hospital, Boston; Department of Neurology (H.C.C., J.M.R.), Keck School of Medicine of USC, Los Angeles, CA; Department of Psychiatry and Human Behavior (S.C., A.K.W.L., S.S.), Memory and Aging Program, Butler Hospital, Brown University Alpert Medical School, Providence, RI; Center for Neuroimaging, Department of Radiology and Imaging Science (M.R.F., A.J.S.), Department of Pathology and Laboratory Medicine (B.G.), and Indiana Alzheimers Disease Research Center (A.J.S.), Indiana University School of Medicine, Indianapolis; Departments of Molecular Imaging and Neurology (M.F.), Royal Prince Alfred Hospital, University of Sydney, Australia; Department of Neurology (N.R.G.-R.), Mayo Clinic, Jacksonville, FL; German Center for Neurodegenerative Diseases (DZNE) (C.L., J.L., I.Y.); Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy (C.L.), University of Tübingen; Department of Neurology (J.L., I.Y.), Ludwig-Maximilians-Universität München; Munich Cluster for Systems Neurology (SyNergy) (J.L., I.Y.), Germany; Florey Institute and The University of Melbourne (C.L.M.), Australia; Department of Neurology (J.M.N.), Columbia University Irving Medical Center, New York, NY; Department of Radiology (K.K., C.R.J., G.M.P.), Mayo Clinic, Rochester, MN; Department of Molecular Imaging and Therapy (C.C.R., V.L.V.), Austin Health, University of Melbourne, Heidelberg, Australia; Clinical Research Center for Dementia (H.S.), Osaka City University; Department of Neurology (M.S.), Hirosaki University Graduate School of Medicine; and Department of Neurology (K.S.), The University of Tokyo, Japan.

Objective: To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we longitudinally evaluated families with dominantly inherited Alzheimer disease (DIAD).

Methods: Mutation carriers (n = 310) and noncarriers (n = 201) underwent neuroimaging, including gradient echo MRI sequences to detect CMHs, and neuropsychological and clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical markers of disease.

Results: Three percent of noncarriers and 8% of carriers developed CMHs primarily located in lobar areas. Carriers with CMHs were older, had higher diastolic blood pressure and Hachinski ischemic scores, and more clinical, cognitive, and motor impairments than those without CMHs. ε4 status was not associated with the prevalence or incidence of CMHs. Prevalent or incident CMHs predicted faster change in Clinical Dementia Rating although not composite cognitive measure, cortical thickness, hippocampal volume, or white matter lesions. Critically, the presence of 2 or more CMHs was associated with a significant risk for development of additional CMHs over time (8.95 ± 10.04 per year).

Conclusion: Our study highlights factors associated with the development of CMHs in individuals with DIAD. CMHs are a part of the underlying disease process in DIAD and are significantly associated with dementia. This highlights that in participants in treatment trials exposed to drugs, which carry the risk of ARIA-H as a complication, it may be challenging to separate natural incidence of CMHs from drug-related CMHs.
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http://dx.doi.org/10.1212/WNL.0000000000011542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032370PMC
March 2021

Comparing cortical signatures of atrophy between late-onset and autosomal dominant Alzheimer disease.

Neuroimage Clin 2020 5;28:102491. Epub 2020 Nov 5.

Department of Radiology, Department of Neurology, Department of Psychiatry, Department of Pathology and Immunology, Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO, USA.

Defining a signature of cortical regions of interest preferentially affected by Alzheimer disease (AD) pathology may offer improved sensitivity to early AD compared to hippocampal volume or mesial temporal lobe alone. Since late-onset Alzheimer disease (LOAD) participants tend to have age-related comorbidities, the younger-onset age in autosomal dominant AD (ADAD) may provide a more idealized model of cortical thinning in AD. To test this, the goals of this study were to compare the degree of overlap between the ADAD and LOAD cortical thinning maps and to evaluate the ability of the ADAD cortical signature regions to predict early pathological changes in cognitively normal individuals. We defined and analyzed the LOAD cortical maps of cortical thickness in 588 participants from the Knight Alzheimer Disease Research Center (Knight ADRC) and the ADAD cortical maps in 269 participants from the Dominantly Inherited Alzheimer Network (DIAN) observational study. Both cohorts were divided into three groups: cognitively normal controls (n = 381; n = 145), preclinical (n = 153; n = 76), and cognitively impaired (n = 54; n = 48). Both cohorts underwent clinical assessments, 3T MRI, and amyloid PET imaging with either C-Pittsburgh compound B or F-florbetapir. To generate cortical signature maps of cortical thickness, we performed a vertex-wise analysis between the cognitively normal controls and impaired groups within each cohort using six increasingly conservative statistical thresholds to determine significance. The optimal cortical map among the six statistical thresholds was determined from a receiver operating characteristic analysis testing the performance of each map in discriminating between the cognitively normal controls and preclinical groups. We then performed within-cohort and cross-cohort (e.g. ADAD maps evaluated in the Knight ADRC cohort) analyses to examine the sensitivity of the optimal cortical signature maps to the amyloid levels using only the cognitively normal individuals (cognitively normal controls and preclinical groups) in comparison to hippocampal volume. We found the optimal cortical signature maps were sensitive to early increases in amyloid for the asymptomatic individuals within their respective cohorts and were significant beyond the inclusion of hippocampus volume, but the cortical signature maps performed poorly when analyzing across cohorts. These results suggest the cortical signature maps are a useful MRI biomarker of early AD-related neurodegeneration in preclinical individuals and the pattern of decline differs between LOAD and ADAD.
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http://dx.doi.org/10.1016/j.nicl.2020.102491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689410PMC
June 2021

Environmental factors between normal and superagers in an Argentine cohort.

Dement Neuropsychol 2020 Dec;14(4):345-349

Departamento de Neurología, FLENI Ringgold Standard Institution - Buenos Aires, Argentina.

Normal aging usually brings age-related cognitive decline. However, there is a group of aged individuals who have exceptional memory performance: the superagers.

Objective: Our aim was to identify the environmental factors that could influence exceptional memory performance in a cohort of Argentine individuals.

Methods: Forty healthy volunteers >80 years of age were classified into two groups, superagers (SA, n=20) and normal agers (NA, n=20), according to the Northwestern SuperAging Program criteria. Participants were neuropsychologically tested and evaluated on environmental aspects: working status, education, bilingualism, cognitive reserve, physical activity, social networking, clinical comorbidities, and longevity of parents and siblings.

Results: Both groups were highly educated (NA=16.3±3 years; SA 15.85±2.6; p=0.6), 11.8% of the sample was still working without differences between groups. There were no differences in cognitive reserve inventory (p=0.7), physical activity engagement (p=0.423), or social network index (p=0.73). As for longevity, 44% of the siblings lived longer than 80 years of age (p=0.432) and maternal longevity was linked to SA (NA=46.7%; SA=80%; p=0.045).

Conclusions: This study is a pilot approximation to the superaging population in Argentina. Our results suggest that environmental factors related to successful aging do not differentiate superaging. SA may depend on variables yet to be identified, probably of a genetic/metabolic order.
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http://dx.doi.org/10.1590/1980-57642020dn14-040003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735051PMC
December 2020

Dominantly inherited Alzheimer's disease in Latin America: Genetic heterogeneity and clinical phenotypes.

Alzheimers Dement 2021 04 23;17(4):653-664. Epub 2020 Nov 23.

Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.

Introduction: A growing number of dominantly inherited Alzheimer's disease (DIAD) cases have become known in Latin American (LatAm) in recent years. However, questions regarding mutation distribution and frequency by country remain open.

Methods: A literature review was completed aimed to provide estimates for DIAD pathogenic variants in the LatAm population. The search strategies were established using a combination of standardized terms for DIAD and LatAm.

Results: Twenty-four DIAD pathogenic variants have been reported in LatAm countries. Our combined dataset included 3583 individuals at risk; countries with highest DIAD frequencies were Colombia (n = 1905), Puerto Rico (n = 672), and Mexico (n = 463), usually attributable to founder effects. We found relatively few reports with extensive documentation on biomarker profiles and disease progression.

Discussion: Future DIAD studies will be required in LatAm, albeit with a more systematic approach to include fluid biomarker and imaging studies. Regional efforts are under way to extend the DIAD observational studies and clinical trials to Latin America.
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http://dx.doi.org/10.1002/alz.12227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140610PMC
April 2021

Biphasic cortical macro- and microstructural changes in autosomal dominant Alzheimer's disease.

Alzheimers Dement 2021 04 16;17(4):618-628. Epub 2020 Nov 16.

Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

Introduction: A biphasic model for brain structural changes in preclinical Alzheimer's disease (AD) could reconcile some conflicting and paradoxical findings in observational studies and anti-amyloid clinical trials.

Methods: In this study we tested this model fitting linear versus quadratic trajectories and computed the timing of the inflection points vertexwise of cortical thickness and cortical diffusivity-a novel marker of cortical microstructure-changes in 389 participants from the Dominantly Inherited Alzheimer Network.

Results: In early preclinical AD, between 20 and 15 years before estimated symptom onset, we found increases in cortical thickness and decreases in cortical diffusivity followed by cortical thinning and cortical diffusivity increases in later preclinical and symptomatic stages. The inflection points 16 to 19 years before estimated symptom onset are in agreement with the start of tau biomarker alterations.

Discussion: These findings confirm a biphasic trajectory for brain structural changes and have direct implications when interpreting magnetic resonance imaging measures in preventive AD clinical trials.
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http://dx.doi.org/10.1002/alz.12224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043974PMC
April 2021

COVID-19 Epidemic in Argentina: Worsening of Behavioral Symptoms in Elderly Subjects With Dementia Living in the Community.

Front Psychiatry 2020 28;11:866. Epub 2020 Aug 28.

Memory and Ageing Center, Department of Cognitive Neurology, Neuropsychiatry and Neuropsychology, Fleni. Fundación para el estudio de enfermedades neurológicas de la infancia, Buenos Aires, Argentina.

In Argentina, the quality of care that elderly subjects with dementia living in the community received has been deeply affected by COVID-19 epidemic. Our objective was to study to what extend mandatory quarantine imposed due to COVID-19 had affected behavioral symptoms in subjects with dementia after the first 8 weeks of quarantine. We invited family members to participate in a questionnaire survey. The sample consisted of family caregivers (n = 119) of persons with AD or related dementia living at home. We designed a visual analog scale to test the level of the burden of care of family members. Items inquired in the survey included type and setting (home or day care center) of rehabilitation services (physical/occupational/cognitive rehabilitation) and change in psychotropic medication and in behavioral symptoms that subjects with dementia experienced before and during the epidemic. Characteristics of people with dementia and their caregivers were analyzed with descriptive statistics using the chi-square tests, p < 0.01 was considered significant. Results: The sample included older adults with dementia. Mean age: 81.16 (±7.03), 35% of the subjects had more than 85 years of age. Diagnosess were 67% Alzheimer´s dementia and 26% mixed Alzheimer´s disease (AD). Stages were 34.5% mild cases, 32% intermediate stage, and 33% severe cases as per Clinical dementia Rating score. In 67% of the sample, a family member was the main caregiver. Important findings were increased anxiety (43% of the sample), insomnia (28% of the subjects), depression (29%), worsening gait disturbance (41%), and increase use of psychotropics to control behavioral symptoms. When we compared the frequency of behavioral symptoms within each dementia group category, we found that anxiety, depression, and insomnia were more prevalent in subjects with mild dementia compared to subjects with severe dementia. We analyzed the type and pattern of use of rehabilitation services before and during the isolation period, and we observed that, as a rule, rehabilitation services had been discontinued in most subjects due to the quarantine. We concluded from our analysis that during COVID-19 epidemic there was a deterioration of behavioral symptoms in our population of elderly dementia subjects living in the community. Perhaps, our findings are related to a combination of social isolation, lack of outpatient rehabilitation services, and increased stress of family caregivers. It is necessary to develop a plan of action to help dementia subjects deal with the increased stress that this epidemic imposed on them.
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http://dx.doi.org/10.3389/fpsyt.2020.00866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485090PMC
August 2020
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