Patricio Chrem Mendez

Cognitive reserve and Aβ1-42 in mild cognitive impairment (Argentina-Alzheimer’s Disease Neuroimaging Initiative)

Background The purpose of this study was to investigate the relationship between cognitive reserve and concentration of Aβ1-42 in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment, those with Alzheimer’s disease, and in control subjects. Methods Thirty-three participants from the Argentina-Alzheimer’s Disease Neuroimaging Initiative database completed a cognitive battery, the Cognitive Reserve Questionnaire (CRQ), and an Argentinian accentuation reading test (TAP-BA) as a measure of premorbid intelligence, and underwent lumbar puncture for CSF biomarker quantification. Results The CRQ significantly correlated with TAP-BA, education, and Aβ1-42. When considering Aβ1-42 levels, significant differences were found in CRQ scores; higher levels of CSF Aβ1-42 were associated with higher CRQ scores. Conclusion Reduced Aβ1-42 in CSF is considered as evidence of amyloid deposition in the brain. Previous results suggest that individuals with higher education, higher occupational attainment, and participation in leisure activities (cognitive reserve) have a reduced risk of developing Alzheimer’s disease. Our results support the notion that enhanced neural activity has a protective role in mild cognitive impairment, as evidenced by higher CSF Aβ1-42 levels in individuals with more cognitive reserve.

Predicting episodic memory performance using different biomarkers: results from Argentina-Alzheimer's Disease Neuroimaging Initiative.

Purpose Argentina-Alzheimer’s Disease Neuroimaging Initiative (Arg-ADNI) is the first ADNI study to be performed in Latin America at a medical center with the appropriate infrastructure. Our objective was to describe baseline characteristics and to examine whether biomarkers related to Alzheimer’s disease (AD) physiopathology were associated with worse memory performance. Patients and methods Fifteen controls and 28 mild cognitive impairment and 13 AD dementia subjects were included. For Arg-ADNI, all biomarker parameters and neuropsychological tests of ADNI-II were adopted. Results of positron emission tomography (PET) with fluorodeoxyglucose and 11C-Pittsburgh compound-B (PIB-PET) were available from all participants. Cerebrospinal fluid biomarker results were available from 39 subjects. Results A total of 56 participants were included and underwent baseline evaluation. The three groups were similar with respect to years of education and sex, and they differed in age (F=5.10, P=0.01). Mean scores for the baseline measurements of the neuropsychological evaluation differed significantly among the three groups at P<0.001, showing a continuum in their neuropsychological performance. No significant correlations were found between the principal measures (long-delay recall, C-Pittsburgh compound-B scan, left hippocampal volume, and APOEε4) and either age, sex, or education (P>0.1). Baseline amyloid deposition and left hippocampal volume separated the three diagnostic groups and correlated with the memory performance (P<0.001). Conclusion Cross-sectional analysis of baseline data revealed links between cognition, structural changes, and biomarkers. Follow-up of a larger and more representative cohort, particularly analyzing cerebrospinal fluid and brain biomarkers, will allow better characterization of AD in our country.

Argentina ADNI: Preliminary report on CSF biomarkers

Background: The majority of individuals referred to a Memory Clinic have subtle symptoms of cognitive impairment and from a clinical point of view most of them are not demented. Eventually, many of these individuals develop a form of dementia that is clinically detectable but some of them may remain stable for years, and the concern may even disappear. The EEG diagnostic tool presented here is designed to help the clinician to evaluate possible progress of the cognitive symptoms in MCI subjects over time. Methods: In an EEG database EEGs from 342 mild AD subjects and 181 MCI individuals have been entered. The EEG data from the MCI individuals was collected over a period of 7 years (20052011). Over the course of 8 years these MCI individuals have been followed up. The MCI individuals were divided into three subgroups according to their clinical status at follow up: prodromal AD (pAD), stable MCI (sMCI), and other. The pAD and sMCI groups were compared by constructing a classifier by applying statistical pattern recognition to a large set of EEG features. Results: Of the 181 MCI individuals 70 were diagnosed with AD 1-7.7 years after the EEG measurement with a mean of 2 years. 79 remainedMCI for at least 3 years, with a mean of 4.75 years and standard deviation of 1.00 year. The remaining 32 individuals had developed other types of dementia at follow up. The pAD-sMCI classifier indicates that using EEG it is possible to predict which of the MCI individuals will at a later time develop AD with accuracy of about 80%. Conclusions: Following amore substantial clinical validation and an easy access to the methodology, we expect this application of clinical EEG in support for differential diagnosis of mild cognitive impairment to become a realistic first step in the full clinical workup of patients who visit a memory clinic. The underlying technology is well known, widely available and inexpensive in relation to other imaging techniques.

Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI): neuropsychological evolution profile after one-year follow up

The Argentina-Alzheimers disease neuroimaging initiative (Arg-ADNI) study is a longitudinal prospective cohort of 50 participants at a single institution in Buenos Aires, Argentina. Longitudinal assessments on a neuropsychological test battery were performed on 15 controls, 24 mild cognitive impairment (MCI) patients and 12 Alzheimers disease (AD) dementia patients. In our study population, there was a high prevalence of positive AD biomarkers in the AD group, 92.3% (12/13); and a low prevalence in the normal controls, 20%; almost half (48%) of the patients diagnosed with MCI had positive amyloid detection. After a one year, the significant differences found at baseline on neuropsychological testing were similar at the follow-up assessment even though the AD group had significantly altered its functional performance (FAQ and CDR). The exception was semantic fluency, which showed greater impairment between the AD group and MCI and normal controls respectively. For these tests, the addition of AD biomarkers as a variable did not significantly alter the variations previously found for the established clinical groups model. Finally, the one-year conversion rate to dementia was 20% in the MCI cohort.

THE A/T/N CLASSIFICATION IN THE PROGNOSIS OF MILD COGNITIVE IMPAIRMENT IN THE ARGENTINE-ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE COHORT

patients were classified based on their baseline CSF biomarker levels as biomarker (BM)-positive or BM-negative. Clinical decline was determined by following the patients over a period of 24 months, based on Mini-Mental State Examination (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB) and Functional Activities Questionnaire (FAQ) scores. The ability of the CSF biomarkers and ratios to separate patients with higher versus lower change in clinical scores was estimated based on a multivariable linear mixed effects model. Time-to-event analyses, including Kaplan-Meier curves, were performed for outcome dementia (follow-up of up to 72 months). Results:MMSE scores showed a significantly stronger decrease in BM-positive compared with BM-negative patients (Table 1, Figure 1). pTau/Ab42 and tTau/ Ab42 ratios performed better as predictors of clinical decline than single biomarkers (Table 1). Similar results were obtained for the other scores (Table 1). Although no clear optimum for the biomarker cut-offs could be identified, good separation was observed between patients with lower and higher risk of progression to dementia for the biomarkers (Figure 2). Conclusions:

CORTICAL THICKNESS FOLLOW-UP AFTER ONE YEAR IN ADNI-ARGENTINA COHORT

P1-451 CORTICALTHICKNESS FOLLOW-UP AFTER ONE YEAR IN ADNI-ARGENTINA COHORT Ismael Luis Calandri, Ignacio Demey, Patricio Alexis Chrem Mendez, Gabriela Cohen, Maria Julieta Russo, Ezequiel Surace, Horacio Martinetto, Federico Nahas, Maria Eugenia Martin, Paula Harris, Jorge Campos, Gustavo Sevlever, Silvia Vazquez, Allegri F. Ricardo, Ra ul Carrea Institute for Neurological Research (FLENI), Buenos Aires, Argentina; Hospital Brit anico de Buenos Aires, Buenos Aires, Argentina; Ra ul Carrea Institute for Neurological Research (FLENI), Buenos Aires, Argentina. Contact e-mail: ismaelcalandri@gmail.com

Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America

Frontotemporal lobar degeneration is a neuropathological disorder that causes a variety of clinical syndromes including frontotemporal dementia (FTD), progressive supranuclear palsy, and corticobasal syndrome (CBS). FTD associated with parkinsonism occurs frequently as a result of mutations in the C9orf72 gene and also in the genes coding for the protein associated with microtubule tau (MAPT) and progranulin (GRN) on chromosome 17 (FTDP-17). Herein, we report an Argentinean family, of Basque ancestry, with an extensive family history of behavioral variant of FTD. Twenty-one members over 6 generations composed the pedigree. An extensive neurologic and neurocognitive examination was performed on 2 symptomatic individuals and 3 nonsymptomatic individuals. Two different phenotypes were identified among affected members, CBS in the proband and FTD in his brother. DNA was extracted from blood for these 5 individuals and whole-exome sequencing was performed on 3 of them followed by Sanger sequencing of candidate genes on the other 2. In both affected individuals, a missense mutation (p.P301L; rs63751273) in exon 10 of the MAPT gene (chr17q21.3) was identified. Among MAPT mutations, p.P301L is the most frequently associated to different phenotypes: (1) aggressive, symmetrical, and early-onset Parkinsonism; (2) late parkinsonism associated with FTD; and (3) progressive supranuclear palsy but only exceptionally it is reported associated to CBS. This is the first report of the occurrence of the p.P301L-MAPT mutation in South America and supports the marked phenotypic heterogeneity among members of the same family as previously reported.

WHAT HAPPENS WHEN TWO AD AMYLOID BIOMARKERS HAVE DISCORDANT RESULTS IN THE SAME PATIENT

DISEASE USING ULTRA-WIDEFIELD IMAGING (UWFI) Lajos Csincsik, Erin Flynn, Enrico Pellegrini, Giorgos Papanastasiou, Tom MacGillivray, Craig W. Ritchie, Tunde Peto, Imre Lengyel, Queen’s University Belfast, Belfast, United Kingdom; The George Washington University, Washington DC, USA; University of Edinburgh, Edinburgh, United Kingdom; Queen’s University Belfast, Belfast, United Kingdom. Contact e-mail: lcsincsik01@qub.ac.uk

ADNI: ARGENTINEAN COHORT — ONE-YEAR FOLLOW-UP

P1-182 THEEFFECTOFAPOEE4ONEPISODICMEMORY IN PATIENTSWITHAMNESTICMILDCOGNITIVE IMPAIRMENT Ivana Mokrisova, Jan Laczo, Martina Parizkova, Kamil Vlcek, Martin Vyhnalek, Katerina Sheardova, Vojtech Kaplan, Vaclav Matoska, Ross Andel, Jakob Hort, Memory Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic; 2 International Clinical Research Center, St. Anne’s University Hospital Brno, Brno, Czech Republic; Department of Neurophysiology of Memory, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic; 4 Department of Clinical Biochemistry, Hematology and Immunology, Homolka Hospital, Prague, Czech Republic; School of Aging Studies, University of South Florida, Tampa, FL, USA. Contact e-mail: mokrisova.ivana@gmail.com

HIPPOCAMPAL ATROPHY: AUTOMATED VOLUMETRY VS VISUAL EXAMINATION–AN ARG ADNI COHORT ANALYSIS

the low-probability was positive. The syndromic diagnoses that most discrepancies were found were: amnesticMCI (37% had negative PIB), amnestic and other domains (40%, negative PIB) into high probability group; nonamnestic MCI (33% positive PIB), and non-logopenic PPA and FTD (33% and 45% positive PIB) into low probability group. Normal controls and AD patients (typical and atypical presentation) were the most consistent across clinical and molecular diagnostics. Conclusions: There were discrepancies in molecular diagnosis in both high and low probability groups. The implications of these inconsistencies were different between each clinical category. The most important contribution to the diagnosis of 11C-PIB-PET is really significant in cases of early-onset AD, and atypical presentation (PPA, FTD and PCA).