Jordi Peña-Casanova

Spanish Multicenter Normative Studies (NEURONORMA Project): Methods and Sample Characteristics

This paper describes the methods and sample characteristics of a series of Spanish normative studies (The NEURONORMA project). The primary objective of our research was to collect normative and psychometric information on a sample of people aged over 49 years. The normative information was based on a series of selected, but commonly used, neuropsychological tests covering attention, language, visuo-perceptual abilities, constructional tasks, memory, and executive functions. A sample of 356 community dwelling individuals was studied. Demographics, socio-cultural, and medical data were collected. Cognitive normality was validated via informants and a cognitive screening test. Norms were calculated for midpoint age groups. Effects of age, education, and sex were determined. The use of these norms should improve neuropsychological diagnostic accuracy in older Spanish subjects. These data may also be of considerable use for comparisons with other normative studies. Limitations of these normative data are also commented on.

Spanish Multicenter Normative Studies (NEURONORMA Project): Norms for Verbal Fluency Tests

Lexical fluency tests are frequently used in clinical practice to assess language and executive function. As part of the Spanish multicenter normative studies (NEURONORMA project), we provide age- and education-adjusted norms for three semantic fluency tasks (animals, fruit and vegetables, and kitchen tools), three formal lexical tasks (words beginning with P, M, and R), and three excluded letter fluency tasks (excluded A, E, and S). The sample consists of 346 participants who are cognitively normal, community dwelling, and ranging in age from 50 to 94 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. The current norms should provide clinically useful data for evaluating elderly Spanish people. These data may also be of considerable use for comparisons with other international normative studies. Finally, these norms should help improve the interpretation of verbal fluency tasks and allow for greater diagnostic accuracy.

Manual validation of FreeSurfer's automated hippocampal segmentation in normal aging, mild cognitive impairment, and Alzheimer Disease subjects

Hippocampal volume is reduced in Alzheimer Disease (AD) and has been proposed as a possible surrogate biomarker to aid early diagnosis. Whilst automated methods to segment the hippocampus from magnetic resonance images are available, manual segmentation, in spite of being time-consuming and unsuitable for large samples, is still the standard. In order to study the validity of FreeSurfers automated method, we compared hippocampal automated measures with manual tracing in a sample composed of healthy elderly (N=41), Mild Cognitive Impairment (MCI) (N=23), and AD (N=25) subjects. Percent volume overlap, percent volume difference, correlations, and Bland-Altman plots were studied. Automated measures were slightly larger than hand tracing ones (mean difference 10%). Percent volume overlap showed good results, but was far from perfect (78%). Manual and automated volume correlations were approximately 0.84 and the Bland-Altman analysis showed acceptable interchangeability of methods. Within-group analysis demonstrated that patient samples obtained smaller values in validity indexes than controls. Globally, FreeSurfers automated hippocampal volumetry showed adequate validity when compared to manual tracing, with a tendency to overestimation. Nevertheless, the greater difference between automated and manual segmentation in atrophic brains suggests that studies in AD based on this software could be more likely to produce false negatives.

Spanish Multicenter Normative Studies (NEURONORMA Project): Norms for Verbal Span, Visuospatial Span, Letter and Number Sequencing, Trail Making Test, and Symbol Digit Modalities Test

As part of the Spanish Multicenter Normative Studies (NEURONORMA project), we provide age- and education-adjusted norms for the following instruments: verbal span (digits), visuospatial span (Corsis test), letter-number sequencing (WAIS-III), trail making test, and symbol digit modalities test. The sample consists of 354 participants who are cognitively normal, community-dwelling, and age ranging from 50 to 90 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. The current norms should provide clinically useful data for evaluating elderly Spanish people. These data may be of considerable use for comparisons with other normative studies. Limitations of these normative data are mainly related to the techniques of recruitment and stratification employed.

Spanish Multicenter Normative Studies (NEURONORMA Project): Norms for the Rey–Osterrieth Complex Figure (Copy and Memory), and Free and Cued Selective Reminding Test

The Rey-Osterrieth complex figure (ROCF) and the free and cued selective reminding test (FCSRT) are frequently used in clinical practice. The ROCF assesses visual perception, constructional praxis, and visuospatial memory, and the FCSRT assesses verbal learning and memory. As part of the Spanish Normative Studies (NEURONORMA), we provide age- and education-adjusted norms for the ROCF (copy and memory) and for the FCSRT. The sample consists of 332 and 340 participants, respectively, who are cognitively normal, community dwelling, and ranging in age from 50 to 94 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. Although age and education affected the score of the ROCF and FCSRT, sex was found to be unrelated in this normal sample. The normative data presented here were obtained from the same study sample as all other NEURONORMA norms and the same statistical procedures were applied. These co-normed data will allow clinicians to compare scores from one test with all the tests included in the project.

Clinical Validity and Utility of the Interview for Deterioration of Daily Living in Dementia for Spanish-Speaking Communities

The assessment of activities of daily living is a central procedure in the diagnosis of dementia. Few instruments in the field allow for early detection of functional decline because the items they use refer mainly to basic activities of daily living (BADL), which do not become compromised until later in the disease process. The Interview for Deterioration of Daily Living in Dementia (IDDD) may be a valuable tool for early detection of functional decline because it includes, apart from a BADL subscale, another subscale containing a variety of instrumental activities of daily living (LADL), which are the first to be affected in dementing processes. We present an adaptation and validation of the IDDD for Spanish-speaking communities (S-IDDD). A total of 254 control subjects (CONT), 86 patients with mild memory/cognitive impairment with no dementia (CIND), and 111 patients diagnosed with probable dementia of the Alzheimer type (DAT) participated in this project. IDDD total scores (mean and SD) were as follow: CONT: 33.1 (0.4); CIND: 35.2 (3.4); DAT: 54.3 (18.6). The present validation showed no sociodemographic effects on the IDDD total scores. The IDDD demonstrated great internal consistency (alpha = .985) and reproducibility (intraclass correlation coefficient = .94). Correlations were high (r = .81; p < .1) when they took into account the whole sample, but decreased significantly when the groups were separated by pathologic condition. The scale showed significant differences between DAT versus CIND and CONT. The IADL subscale differentiated all three groups, which makes it extremely valuable for early detection of functional decline. The present study shows that the S-IDDD is a reliable adaptation of the original IDDD scale and may be used successfully in Spanish populations for staging and follow-up of subjects with dementia.

Cognitive performance in recreational ecstasy polydrug users: a two-year follow-up study

There is important preclinical evidence of long lasting neurotoxic and selective effects of ecstasy MDMA on serotonin systems in non-human primates. In humans long-term recreational use of ecstasy has been mainly associated with learning and memory impairments. The aim of the present study was to investigate the neuropsychological profile associated with ecstasy use within recreational polydrug users, and describe the cognitive changes related to maintained or variable ecstasy use along a two years period. We administered cognitive measures of attention, executive functions, memory and learning to three groups of participants: 37 current polydrug users with regular consumption of ecstasy and cannabis, 23 current cannabis users and 34 non-users free of illicit drugs. Four cognitive assessments were conducted during two years. At baseline, ecstasy polydrug users showed significantly poorer performance than cannabis users and non-drug using controls in a measure of semantic word fluency. When ecstasy users were classified according to lifetime use of ecstasy, the more severe users (more than 100 tablets) showed additional deficits on episodic memory. After two years ecstasy users showed persistent deficits on verbal fluency, working memory and processing speed. These findings should be interpreted with caution, since the possibility of premorbid group differences cannot be entirely excluded. Our findings support that ecstasy use, or ecstasy/cannabis synergic effects, are responsible for the sub-clinical deficits observed in ecstasy polydrug users, and provides additional evidence for long-term cognitive impairment owing to ecstasy consumption in the context of polydrug use.

Spanish Multicenter Normative Studies (NEURONORMA Project): Norms for Boston Naming Test and Token Test

As part of the Spanish Multicenter Normative Studies (NEURONORMA project), we provide age- and education-adjusted norms for the Boston naming test and Token test. The sample consists of 340 and 348 participants, respectively, who are cognitively normal, community-dwelling, and ranging in age from 50 to 94 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. Age and education affected the score of the both tests, but sex was found to be unrelated to naming and verbal comprehension efficiency. Our norms should provide clinically useful data for evaluating elderly Spaniards. The normative data presented here were obtained from the same study sample as all the other NEURONORMA norms and the same statistical procedures for data analyses were applied. These co-normed data allow clinicians to compare scores from one test with all tests.

Spanish Multicenter Normative Studies (NEURONORMA Project): norms for the Stroop color-word interference test and the Tower of London-Drexel.

As part of the NEURONORMA project, we provide age- and education-adjusted norms for the Stroop color-word interference test (SCWT)-Golden version and the Tower of London-Drexel University version (TOL(DX)). The sample consists of 344 and 347 participants, respectively, who are cognitively normal, community dwelling, and ranging in age from 50 to 90 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. Demographic variables, age, and education significantly affect scores of the SWCT and TOL(DX), sex, however, was found to be unrelated to performance in this sample. The normative data presented here were obtained from the same study sample as all the other NEURONORMA tests. In addition, the same statistical procedures for data analyses were applied. These co-normed data allow clinicians to compare scores from one test with all tests.

A Randomized, Double-blind, Placebo Controlled-trial of Triflusal in Mild Cognitive Impairment: The Trimci Study

BackgroundAmnestic mild cognitive impairment represents, in many cases, the earliest clinical phases of Alzheimer disease. Anti-inflammatory agents have epidemiologic support as drugs potentially beneficial in Alzheimer disease. In vivo studies have shown that Triflusal and its active metabolite 2-hydroxy-4-trifluoromethyl-benzoic acid have potent anti-inflammatory actions in the central nervous system. MethodsWe conducted a randomized, double-blind, placebo-controlled trial of Triflusal in patients with amnestic mild cognitive impairment. Subjects were randomly assigned to receive 900 mg of Triflusal or placebo for 18 months. The primary outcome was a change in Cognitive subscale of the Alzheimer Disease Assessment Scale; conversion to dementia was a secondary outcome. ResultsA slow rate of recruitment forced a premature cessation of the study. Two hundred and fifty-seven subjects were enrolled and followed-up for an average of 13 months. The significance level was not reached for the primary outcome even though a trend in favor of Triflusal was observed. However, there was a significant difference in the probability of progression to dementia of Alzheimers type with a lower risk in the Triflusal compared with the placebo group (hazard ratio, 2.10; 95% confidence interval, 1.10-4.01; P=0.024). ConclusionsIn this study, Triflusal therapy was associated with a significant lower rate of conversion to dementia that is likely to be clinically relevant. Because the trial was prematurely halted, these results should be interpreted with caution and require further confirmation.