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The aim of this study was to characterize the neuropsychological and neuroimaging profiles of mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients, and to study the magnitude of the differences by comparing both outcomes with healthy subjects in a cross-sectional manner. Five hundred and thirty-five subjects (356 cognitively normal adults (CONT), 79 MCI, and 100 AD) were assessed with the NEURONORMA neuropsychological battery. Thirty CONT, 23 MCI, and 23 AD subjects from this sample were included in the neuroimaging substudy. Patients' raw cognitive scores were converted to age and education-adjusted scaled ones (range 2-18) using co-normed reference values. Medians were plotted to examine the cognitive profile. MRIs were processed by means of FreeSurfer. Effect size indices (Cohen's d) were calculated in order to compare the standardized differences between patients and healthy subjects. Graphically, the observed cognitive profiles for MCI and AD groups produced near to parallel lines. Verbal and visual memories were the most impaired domains in both groups, followed by executive functions and linguistic/semantic ones. The largest effect size between AD and cognitively normal subjects was found for the FCSRT (d = 4.05, AD versus CONT), which doubled the value obtained by the best MRI measure, the right hippocampus (d = 1.65, AD versus CONT). Our results support the notion of a continuum in cognitive profile between MCI and AD. Neuropsychological outcomes, in particular the FCSRT, are better than neuroimaging ones at detecting differences among subjects.

The adverse effects of cannabis use on executive functions are still controversial, fostering the need for novel biomarkers able to unveil individual differences in the cognitive impact of cannabis consumption. Two common genetic polymorphisms have been linked to the neuroadaptive impact of Δ9-tetrahydrocannabinol (THC) exposure and to executive functions in animals: the catechol-O-methyltransferase (COMT) gene val158met polymorphism and the SLC6A4 gene 5-HTTLPR polymorphism. We aimed to test if these polymorphisms moderate the harmful effects of cannabis use on executive function in young cannabis users. We recruited 144 participants: 86 cannabis users and 58 non-drug user controls. Both groups were genotyped and matched for genetic makeup, sex, age, education, and IQ. We used a computerized neuropsychological battery to assess different aspects of executive functions: sustained attention (CANTAB Rapid Visual Information Processing Test, RVIP), working memory (N-back), monitoring/shifting (CANTAB ID/ED set shifting), planning (CANTAB Stockings of Cambridge, SOC), and decision-making (Iowa Gambling Task, IGT). We used general linear model-based analyses to test performance differences between cannabis users and controls as a function of genotypes. We found that: (i) daily cannabis use is not associated with executive function deficits; and (ii) COMT val158met and 5-HTTLPR polymorphisms moderate the link between cannabis use and executive performance. Cannabis users carrying the COMT val/val genotype exhibited lower accuracy of sustained attention, associated with a more strict response bias, than val/val non-users. Cannabis users carrying the COMT val allele also committed more monitoring/shifting errors than cannabis users carrying the met/met genotype. Finally, cannabis users carrying the 5-HTTLPR s/s genotype had worse IGT performance than s/s non-users. COMT and SLC6A4 genes moderate the impact of cannabis use on executive functions.

The retrogenesis model states that the progression of brain aging and Alzheimer's disease (AD) deterioration proceeds inversely to human ontogenic acquisition patterns. Our aim was to assess if the progressive decline of cognitive abilities and functional capacity in AD follows an inverse sequence of acquisition compared to normal developmental patterns. One hundred eighty one children ranging in age from 4 to 12 years and 148 adults (cognitively normal, subjects with mild cognitive impairment, and mild-moderately severe AD) were assessed with the same cognitive and functional tools. The statistical analyses showed a progressive and inverse distribution on cognitive, functional, and mental age scores when comparing results of children classified by chronological age and patients by dementia staging. The pattern of cognitive acquisition in children showed a progressive development of overall cognitive function along all age ranges, in addition to a simultaneous acquisition of instrumental and basic daily living activities in the functional domain. AD patients showed a progressive decline in cognitive and functional domains, which concurs with the sequence of impairment reported in this dementia. Our findings provide support to the inverse and progressive pattern of functional and cognitive decline observed in AD patients compared to the developmental acquisition of these capacities in children, as stated by the retrogenesis model. Nonetheless, certain differences should be considered when comparing the sequence of acquisition during ontogenic development with that of progressive loss during the course of AD. Retrogenesis may account for the progressive loss of neocortical-related functions in AD.

Objective Serial cognitive assessments are useful for many purposes, such as monitoring cognitive decline or evaluating the result of an intervention. In order to determine if an observed change is reliable and meaningful, longitudinal reference data from non-clinical samples are needed. Since neuropsychological outcomes are affected by language and cultural background, cognitive tests should be adapted, and country-based norms collected. The lack of cross-sectional normative data for Spanish population has been partially remediated, but there is still a need of reliable change norms. This paper aims to give an initial response to this need by providing several reliable change indices (RCI) for 1-year follow-up in a Spanish sample. Method A longitudinal observational study was designed. A total of 122 healthy subjects over age 50 were evaluated twice (M = 369.5, SD= 10.7 days) with the NEURONORMA battery. Scores changes were analyzed, and simple discrepancy scores, standard deviation indices, RCI, and standardized regression-based scores were calculated. Results Significant improvements were observed in variables related to memory, both verbal and visual, visuospatial function, and the completion time of complex problems. Reference tables for several RCI are provided for their use in clinical settings. Conclusions Our results confirm the existence of heterogeneous practice effects after 1 year, and support the recommendation of using reliable change norms to avoid misdiagnosis in repeated assessments. This study provides with initial, preliminary norms of cognitive change for its use in Spanish elders. Further studies on larger samples and different inter-visit intervals are still needed.

Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use.Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 min. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results.The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI. The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce - but never substitute - clinical judgment, patient-doctor communication, and inter-professional dialogue.

Lexical fluency tests are frequently used in clinical practice to assess language and executive function.As part of the Spanish normative studies project in young adults (NEURONORMA young adults project), we provide age- and education-adjusted normative data for 3 semantic fluency tasks (animals, fruits and vegetables, and kitchen tools), three formal lexical fluency tasks (words beginning with P, M and R), three excluded-letter fluency tasks (words excluding A, E and S) and a verb fluency task.The sample consisted of 179 participants who are cognitively normal and range in age from 18 to 49 years. Tables are provided to convert raw scores to scaled scores. Age- and education-adjusted scores are provided by applying linear regression techniques.The results show that education impacted most of the verbal fluency test scores, with no effects related to age and only minimal effects related to sex.The norms obtained will be extremely useful in the clinical evaluation of young Spanish adults.

Verbal and visuospatial span, Letter-Number Sequencing, Trail Making Test, and Symbol Digit Modalities Test are frequently used in clinical practice to assess attention, executive functions and memory.In the present study, as part of the Spanish normative studies of NEURONORMA young adults Project, normative data adjusted by age and education are provided for digits, Corsi Block-Tapping Task, Letter-Number Sequencing, Trail Making Test, and Symbol Digit Modalities Test.The sample consisted of 179 participants from 18 to 49 years old, who were cognitively normal. Tables to convert raw scores to scaled scores are provided. Age and education adjusted scores are provided by applying linear regressions.Education affected scores in most of the attention tests; age was found to be related to the visuospatial span and to speed of visuomotor tracking, and there was no relationship as regards sex.The data obtained will be useful in the clinical evaluation of young Spanish adults.

In clinical neuropsychology, normative data are necessary to relate the performance of a subject to a reference group. These normative data should be collected from a pertinent population taking into account sociodemographic and cultural factors.This paper describes the methods and sample characteristics of a series of Spanish normative studies on young adults (NEURONORMA young adults Project). The normative information was based on a series of selected, commonly used, neuropsychological tests covering attention, language, visual-perceptual abilities, constructional tasks, memory, and executive functions.A sample of 179 cognitively normal subjects from 18 to 49 years was studied. Demographics, socio-cultural, and medical data were collected. The statistical procedure used in the normative studies is described.Sociodemographic, family background, health habits, medical history and use of drugs are presented.The use of these norms should improve neuropsychological diagnostic accuracy in young Spanish subjects. These data may also be of considerable use for comparisons with other normative studies.

The Boston Naming Test (BNT) and the Token Test (TT) are frequently used in clinical practice to assess naming and comprehension.The aim of this paper is to present normative data for the BNT and for the TT as part of the NEURONORMA young adults Project.A total of 179 Spanish healthy subjects from 18 to 49 years old were evaluated. Tables to convert raw scores to scaled scores are provided. Age- and education- adjusted scores are obtained by applying linear regressions.The results show an effect of education in both tests, and a minimal effect of age and sex.The normative data obtained will be useful in the clinical evaluation of young Spanish adults.

The Rey-Osterrieth Complex Figure (ROCF) and the Free and Cued Selective Reminding Test (FCSRT) are widely used in clinical practice. The ROCF assesses visual perception, constructional praxis, and visuo-spatial memory. The FCSRT assesses verbal learning and memory.In this study, as part of the Spanish normative studies project in young adults (NEURONORMA young adults), we present age- and education-adjusted normative data for both tests obtained by using linear regression techniques.The sample consisted of 179 healthy participants ranging in age from 18 to 49 years. We provide tables for converting raw scores to scaled scores in addition to tables with scores adjusted by socio-demographic factors.The results showed that education affects scores for some of the memory tests and the figure-copying task. Age was only found to have an effect on the performance of visuo-spatial memory tests, and the effect of sex was negligible.The normative data obtained will be extremely useful in the clinical neuropsychological evaluation of young Spanish adults.

The Visual Object and Space Perception Battery (VOSP) and Judgment of Line Orientation tests (JLO) are used in clinical practice to assess visuoperceptual and visuospatial abilities.In this study, as part of the Spanish normative studies project in young adults (NEURONORMA young adults), we present normative data for a short version of the VOSP test and for the JLO test.The sample consisted of 179 participants who are cognitively normal and range in age from 18 to 49 years. Tables are provided to convert raw scores to scaled scores. Education- and sex-adjusted scores were obtained by applying linear regression techniques.Our results show that education and sex only affect scores on the JLO test, and that age has no effect.The normative data obtained will be extremely useful in the clinical evaluation of young Spanish adults.

The short version of the Barcelona Test is a clinical tool that covers a wide spectrum of neuropsychological skills. Since its creation in 1977, it has often been subject of study either for its internal aspects or in validation studies with other cognitive tests. The results indicate that the Barcelona Test is a useful instrument in detecting cognitive impairment.The aim of this study is to measure the testretest reliability and the interrater reliability of the Abbreviated Barcelona Test in normal population.the sample consists of 31 normal subjects (14 men and 17 women) from 20 to 65 years old.Abbreviated Barcelona Test (TBA), Mini-Mental Status Examination (MMSE), Syndrome-Kurztest (SKT) and Interview for Deterioration of Daily living in Dementia (IDDD).descriptive statistics and intraclass correlation coefficient.Test-retest reliability shows good intraclass correlation coefficients with both direct ICC=0.92 (IC 95%: 0.85-0.96) or typified scores ICC=0.79 (IC 95%: 0.61-0.89). Nevertheless, when each of the subtests is considered, correlations clearly show two characteristics: subtest with no or minimal range of scores and subtest with distribution of scores (as is the case of memory and executive function). The intraclass coefficient found for the interrater reliability is ICC =0.99 (IC 95 %: 0.99-0.99) and an alpha of 0.99 which indicate excellent reliability. As a whole, the abbreviated version of the Barcelona Test has excellent test-retest and interrater reliability psychometric characteristics.

The study aimed to investigate the Rapid Disability Rating Scale-2 (RDRS-2) in Alzheimer's disease (AD). Test retest reliability, internal consistency, data of discriminant validity of the scale, correlations with other functional and cognitive measures were analyzed.451 subjects were assessed: 254 healthy controls, 86 with cognitive impairment but no dementia (CIND) and 111 subjects diagnosed of AD. Total and subscales scores of the RDRS-2 were obtained. The total score is the sum of three subscales: activities of daily living, disability, and special problems. To establish its correlation with other functional scales and cognitive instruments, the following tools were applied: Blessed Dementia Rating Scale (BDRS), Interview for the Deterioration of Daily Living in Dementia (IDDD), Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) and the Mini-Mental State Examination (MMSE).lineal multivariate regression analysis. Crossvalidation. ROC curves. Intraclass coefficient. Cronbach's alpha and Pearson's Correlation coefficient.RDRS-2 scores by group were the following (mean and SD): Controls (18.95; 1.64), CIND (20.61; 2.88), and AD (28.96; 9.07). Results from regression analysis 282 demonstrated absence of influence of sociocultural variables such as age and education in RDRS-2 scores. Correlations with other instruments were as following: BDRS, r=0.820; IDDD, r=0.882; ADAS-Cog, r=0.762, and MMSE, r=0.742. Intraclass coefficient was 0.86 and Cronbach's alpha was 0.91. For the RDRS-2 the best cutoff score was 21 (82.88% sensitivity and 88.8% specificity). Area under the ROC curve was 0.92.The Spanish adaptation of the RDRS-2 is free of sociocultural influence, and shows very adequate data on internal consistency and stability. Although not specifically designed for its use in AD it correlates highly and significantly with other functional scales as well as with the degree of cognitive impairment in AD.

This study aims to discover the criterion validity of the Blessed Dementia Rating Scale (BDRS) for the diagnosis of Alzheimer's disease. Different cut-off scores and corresponding diagnostic sensitivities and specificities were established. Test-retest reliability and internal consistency of the BDRS were also analyzed.451 subjects were studied (254 controls, 86 subjects with mild cognitive impairment and 111 patients with Alzheimer's disease).scores from different sections of the Blessed score were obtained. The global score (BBRS-Total) is the result of the sum of the three sections, A (changes in every day activities), B (changes in habits) and C (changes in personality). The sum of parts A and B (BDRS-Mod) were also quantified.ROC curves, intraclass correlation coefficient and Cronbach's alpha.The best cut-off score for the BDRS-Total was 3.5 (sensitivity: 87.39%, and specificity: 90%). For the BDRS-Mod, the best cut-off score was 1.5 (sensitivity: 90%, and specificity: 89%). Area under the ROC curve was 0.964 and 0.963 respectively. Intraclass correlation coefficient was 0.98 and Cronbach's alpha was 0.925.The BDRS has good discriminative validity in terms of sensitivity, specificity and predictive value. It also has good test-retest reliability and internal consistency.

The objective is to establish the existence of possible correlations between cognitive measures using the a-BT, and functional measures in a population of normal to moderately severe demented subjects.A sample of 107 subjects (42 healthy controls, 19 subjects with mild cognitive impairment and 46 patients with probable Alzheimer's disease) were included in the present study. The instruments of the cognitive measure used was the abbreviated Barcelona Test (a-BT), a test of general cognitive function. Apart from that, the following functional scales, evaluating activities of daily living, were used: Rapid Disability Rating Scale-2 (RDRS-2), Blessed Dementia Rating Scale (BDRS), and Interview for Deterioration in Daily living in Dementia (IDDD). The statistical procedures were the correlations between cognitive and functional measures using Pearson's correlation coefficient.The correlations obtained between the cognitive and all functional measures were all highly significant (p0.0001) and consistently high, with correlations ranging between 0.72 and 0.80. Correlations between the a-BT and functional measures of more basic activities of daily living (RDRS-2, BDRS) were lower than those that included instrumental and some advanced activities of daily living (IDDD).The present paper establishes the existence of satisfactory correlations between the functional measures studied and the global scores of the a-BT. These correlations are applicable for groups of subjects with cognitive impairment that does not reach the threshold of a diagnosis of dementia as well as subjects suffering from Alzheimer's disease, at least up to moderately severe cases. The global score of the a-BT allows for some degree of prediction of the functional status of a subject with suspected Alzheimer's disease pathology evaluated.

The Geriatric Evaluation of Relative's Rating Instrument (GERRI) is a scale that evaluates the frequencies of alterations in behavior and functional capacity over a two-week period prior to exploration. The scale depends on the observations done by a relative o first caregiver of the studied subject.To adapt and standardize the GERRI for the use in the Spanish population as a part of a general project to standardized cognitive and functional tests.The scale was administered to 444 subjects: 249 controls, 85 mild memory-cognitive disorders without dementia subjects (DWD) and 110 patients with Alzheimer-type dementia (ATD). An across-sectional statistical study was conducted in our samples stratified by age, gender and education. We evaluated the reliability of repeatability of the test, the internal reliability and the age, sex and education effects on the score of the different subscales. We also took into account the diagnostical validity in the Alzheimer disease and finally we correlated this test results with Mini mental test.The demographic variables age and schooling were found to affect the GERRI subscales differently. Gender did not reach significance. Internal consistency for the GERRI-Social, -Mood and -Cognitive were 0.8620, 0.7647 and 0.9259, respectively.The Spanish version of the GERRI may be applied to Spanish clinical series because of its reliable internal consistency and reproducibility.

Drawings tasks have achieved a very central position in neurology by virtue of their sensitivity to many different kinds of brain lesions. Variables of age and education may significantly affect test performance and therefore should taken into account when developing test norms.To increase the sample of the original version of the Barcelona test (BT) and analyze the results of the drawing task.322 normal subjects (47.1% women and 52.9% males), stratified in 7 groups according to age and education were included in the large sample. Copying subtest of the BT were used. Descriptive statistics and multiple lineal regression were applied to the data.Due to the relevance of age and education on coping drawing tasks (Kruskal-Wallis: p0.001 for age and p0.001 for education). Both variables (age and education) were analyzed using multiple lineal regression in order to establish possible effects of age and/or education for each group (F = 18.073; p0.001). Subjects aged more than 70 had the best adjust to the regression model (R2 = 0.4245; F = 18.07; p0.001; delta R2 = 13.56). Furthermore age has an important role as modulator to the results.Age and education influenced copying drawing performance for raw scores as well as when considering timed performance, in a different way for each studied group. While the correlation of education and performance on copy drawing tasks is a direct one, for age this relation is inverse.

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.

The aim of this study was to define a shortened form of the Barcelona neuropsychological test to be used in clinical neurology. There was a selection of subtests from the original test and descriptive statistics of an enlarged number of normal volunteers. 341 normal subjects were studied, 178 male (52.19%) and 163 female (47.1%). Age mean: 54.80, SD = 17.44. Education: mean 9.0 years, SD: 5.4. Subjects were stratified in five groups considering age and education. Subtest were choose according clinical criteria and considering data from a previous study. Five different age and education scoring profiles were defined. This reduced version of the Barcelona test includes the main neuropsychological areas and it takes only 30-45 minutes administration. The Barcelona test meets practical standards in neuropsychology.

To adequately evaluate patients with 4 neuropsychological deficits a project for norming cognitive and functional instruments that assess dementia (NORMACODEM) was designed. Four hundred fifty-one subjects in three groups: 254 controls, 86 patients with minor memory/cognitive deficits without dementia (DWD) and 111 patients with probable Alzheimer-type dementia (ATD) according to the NINCDS/ADRDA criteria. Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale (ADAS), Abbreviated Barcelona Test (ABT), Global Dementia Staging (GDS), Functional Assessment Staging (FAST), Clinical Dementia Rating (CDR), Rapid Disability Rating Scale-2 (RDRS-2), Blessed Dementia Rating Scale (BDRS), Interview for Deterioration in Daily life in Dementia (IDDD), Geriatric Evaluation by Relatives Rating Instrument (GERRI), Geriatric Depression Scale (GDS), Zung Self-Rating Anxiety Scale (ZSRAS). Descriptive statistics and analysis of variance. The characteristics of the sample were as follows.99 men, 155 women. Mean (SD) age: 64.6 (10.9) years. Mean (SD) educational level: 9.1 (4.9) years. DWD: 42 men, 44 women. Mean (SD) age: 65.8 (8.7) years. Men (SD) educational level: 8.4 (4.4) years. ATD: 48 mean, 63 women. Mean (SD) age: 68.3 (8.0) years. Mean (SD) educational level: 6.2 (4.3) years. The ATD patients were significantly older than the controls. Mean educational level was significantly lower in the ATD group than in the other two.

Evaluation with the geriatric depression scale carried out in 30 patients with Parkinson's disease who did not present subjective complaint of loss of memory or impairment in superior mental function capable of interfering in daily routine showed a high frequency of depression of 50-70% depending on where the cut-off in the geriatric depression scale was located. Depression in these patients does not significantly relate with either cognitive impairment or the degree of motor incapacity. Neither were depression or anxiety in these patients related with demographic data such as the age of the patient, age at onset of the disease, sex, months of evolution, or education. In contrast, a positive correlation was found between depression and anxiety.