María Julieta Russo

Analysis of C9orf72 in patients with frontotemporal dementia and amyotrophic lateral sclerosis from Argentina

Pathologic expansion of the G4C2 repeat in C9orf72 is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). To evaluate the frequency of the G4C2 expansion in a Latin American cohort of FTD and ALS patients, we used a 2-step genotyping strategy. For FTD, we observed an overall expansion frequency of 18.2% (6 of 33 unrelated cases). Moreover, the C9orf72 expansion accounted for 37.5% of all familial FTD cases (6 of 16 families). The expansion frequency in sporadic ALS cases was 2% (1 of 47 unrelated patients), whereas we observed the expansion in 1 of 3 families with a positive history for ALS. Overall, the expansion frequency in our FTD group was similar to that reported for patients in Europe and North America, whereas the frequency in our sporadic ALS group was significantly lower. To our knowledge, this is the first report on the frequency of the C9orf72 expansion in a Latin American population.

Diagnostic accuracy of the Phototest for cognitive impairment and dementia in Argentina

Phototest is a simple, easy and very brief test with theoretical advantages over available dementia screening tests in Spain. The objective of this study was to estimate the diagnostic accuracy of the Phototest for cognitive impairment and dementia and to compare it with that of the MMSE and the Clock Drawing Test (CDT) in an Argentine population. A phase II cross-sectional study of diagnostic tests evaluation was performed in a sample of 30 controls, 61 with amnestic mild cognitive impairment (a-MCI), and 56 with mild Alzheimer type dementia (DAT). The diagnostic accuracy (DA) was assessed in relation to the clinical diagnosis by calculating the area under the ROC curve (UAC), Sensitivity (Sn), and Specificity (Sp).The DA of the Phototest for a-MCI and DAT (0.93 and 0.97 [UAC]) was higher than that of the MMSE and the CDT. The cut-off points of 27/28 for DAT (Sn = 89.29 [78.1–96.0], Sp = 96.67 [82.8–99.9]) and 30/31 for a-MCI (Sn = 85.25 [73.8–93.0], Sp = 90.00 [73.5–97.9]) maximized the sum of Sn and Sp. Phototest correlates significantly with MMSE and CDT. The Phototest is an efficient instrument for the detection of mild dementia or MCI, with good accuracy and good correlation with tests measuring overall cognitive impairment.

Creation of the Argentina-Alzheimer's Disease Neuroimaging Initiative

The Alzheimers Disease Neuroimaging Initiative (ADNI) is a multisite, longitudinal study that assesses clinical, imaging, genetic, and biospecimen biomarkers through the process of normal aging to mild cognitive impairment and dementia. We present the creation of the Argentina‐ADNI—the first South American ADNI—and its effort to acquire data comparable with those gathered in other worldwide ADNI centers.

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.

A systematic review and meta-analysis of the diagnostic accuracy of the Phototest for cognitive impairment and dementia

The recently developed Phototest is a simple, easy and very brief test for detecting cognitive impairment or dementia. Objective To evaluate the diagnostic accuracy of the Phototest for detecting cognitive impairment or dementia. Methods We used a manually created database to search for studies evaluating the Phototest diagnostic yield and performed an initial meta-analysis to determine sensitivity (Sn) and specificity (Sp) of diagnostic parameters. We also performed a second meta-analysis of individual participant data. Results In total, 6 studies were included in the meta-analysis. For dementia, Sn was 0.85 (95% CI, 0.82-0.88) and Sp 0.87 (95% CI, 0.85-0.99); for cognitive impairment, Sn was 0.80 (95% CI, 0.77-0.92) and Sp 0.88 (95% CI, 0.86-0.90). In the individual data meta-analysis, 1565 subjects were included, where best cut-off points for dementia and for cognitive impairment were 26/27 (Sn=0.89 (95% CI 0.85-0.91), Sp=0.84 (95% CI, 0.82-0.91)) and 28/29 (Sn=0.79 (95% CI, 0.76-0.81), Sp=0.88 (95% CI, 0.86-0.90)), respectively. Conclusion Phototest has good diagnostic accuracy for dementia and cognitive impairment. It is brief, simple and can be used in illiterate persons. This makes it suitable for use in primary care settings and/or in subjects with low educational level.

High-technology augmentative communication for adults with post-stroke aphasia: a systematic review

ABSTRACT Introduction: Augmentative and alternative communication (AAC) systems were introduced into clinical practice by therapists to help compensate for persistent language deficits in people with aphasia. Although, there is currently a push towards an increased focus on compensatory approaches in an attempt to maximize communication function for social interaction, available studies including AAC systems, especially technologically advanced communication tools and systems, known as ‘high-technology AAC’, show key issues and obstacles for these tools to become utilized in mainstream clinical practice. Areas covered: The current review synthesizes communication intervention studies that involved the use of high-technology communication devices to enhance linguistic communication skills for adults with post-stroke aphasia. The review focuses on compensatory approaches that emphasized functional communication. It also summarizes recommendations for the report of studies evaluating high-technology devices that may be potentially relevant for other researchers working with adults with post-stroke aphasia. Expert commentary: Taken together with positive results in heterogeneous studies, high-technology devices represent a compensatory strategy to enhance communicative skills in individuals with post-stroke aphasia. Improvements in the design of studies and reporting of results may lead to better interpretation of the already existing scientific results from aphasia management.

Utility of the Spanish version of the FTLD-modified CDR in the diagnosis and staging in frontotemporal lobar degeneration

INTRODUCTION The Clinical Dementia Rating Scale (CDR) is a tool designed to quantify the severity of dementia symptoms and is also useful to assess disease progression, in Alzheimers disease (AD). A new version of the scale was developed by adding two extra domains that focused on the core aspects of frontotemporal dementia symptomatology, Language and Behavior/Comportment/Personality. OBJECTIVES In this study, we adapted and validated the modified CDR scale in our setting and language (Rioplatense-Spanish). MATERIALS AND METHODS 46 patients with probable AD, 27 behavioral variant of Frontotemporal Dementia (bvFTD), 18 Primary Progressive Aphasia (PPA) and 40 healthy participants were included. The adapted version of the scale was administered by a blind rater who interviewed patients together with patients caregiver. RESULTS Using ROC curves, the domain language and behavior were superior to the memory domain in accuracy for detecting PPA and bvFTD, respectively, but both of them had equivalent diagnostic accuracies for probable AD. Logistic regression analyses showed that either the LANG or BEHAV domains significantly improved the discrimination between probable AD, bvFTD and PPA. CONCLUSIONS The Spanish version of the modified CDR adds value for the characterization of the non-amnestic symptoms in patients with neurodegenerative dementias.

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.

Cognitive Vascular Impairment: An Overview of Clinical, Diagnosis, and Treatment

Emphasis has shifted from diagnosis of vascular dementia (VaD) based on restrictive criteria to include a broader spectrum of disease, named “vascular cognitive impairment (VCI).” This construct includes mixed dementia and cognitive impairment with no dementia. While VaD is the second leading cause of cognitive impairment in late life, either alone or in combination with Alzheimer’s disease, the milder form is much more common. The concept of mixed dementia has been included in the clinical diagnosis of VCI. With the advent of amyloid imaging, it will be possible to assess the relative contributions of both pathologies to brain function, thereby further elucidating the combined effects on cognitive aging and dementia risk. Novel neuroimaging methodology to identify biomarkers and risks for vascular injuries associated with VCI are necessary. Given its growing health, social, and economic burden, the prevention and treatment of milder forms of VCI are critical priorities for clinical care and research.

Vascular Cognitive Disorder: A Diagnostic and Pharmacological Treatment Updating

Cognitive impairment underpins some of the clinical spectrum of the cerebrovascular disease (CVD), as well as contributes to the patients impaired social and behavioral functioning, and the higher mortality. When cognitive function is affected by CVD, we name it as vascular cognitive impairment (VCI). The cognitive impairment may be mild, or may be severe enough to warrant a diagnosis of dementia. Pure vascular dementia is not common. Because of that the concept of mixed dementia has been included in the clinical diagnosis of VCI. Despite a general emphasis in the international literature on the primary and secondary prevention of CVD to avoid vascular dementia or their combination with Alzheimers disease, the controversy concerning their diagnostic criteria and optimal treatment is still open. Given its growing burden, the prevention and treatment of CVD and the spectrum of VCI are critical priorities for clinical care and research. We performed a selective review about the current status of vascular dementia, mild cognitive impairment due to CVD, and mixe d dementia, with special emphasis on available evidence of pharmacological strategies for treatment and prevention from controlled clinical trials.