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The application of the Boston Naming Test (BNT) is time-consuming and shortened versions need to be developed for screening purposes. The aims of this study were to develop four equivalent 15-item forms of a Spanish adaptation of the BNT, to test the equivalence of the new versions in a clinical sample, and to provide normative data. The normative sample consisted of 340 subjects. The clinical sample included 172 patients (76 Mild Cognitive Impairment and 96 Alzheimer's disease). An empirical procedure was used to develop the shortened versions. All new versions demonstrated satisfactory internal consistency. Pearson's coefficient analysis showed strong relationships among the four short-form versions as well as between each of them and the 60-item test. The inferential confidence interval method demonstrated the equivalence between the four shortened versions. Age and education affected the score of all short-form versions, but sex was found to be unrelated to the performance. Normative data were calculated for midpoint age groups. This paper proposes four 15-item equivalent versions that could be useful and time-saving tools for screening purposes.

Background: The Alzheimer's Disease Functional Assessment and Change Scale (ADFACS) is a functional assessment instrument widely used in clinical research., Aims: To test the diagnostic and concurrent validity of the Spanish version of this scale and to describe the functional deficit pattern for mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia., Methods: The ADFACS, the Interview for Deterioration in Daily Living Activities in Dementia (IDDD), and the Mini Mental State Examination (MMSE) were administered to 146 control subjects (CS) and 165 patients (67 MCI and 98 AD). Nonparametric tests were used to compare the diagnostic groups. Cronbach's α and correlations with the MMSE and the IDDD were calculated. Sensitivity, specificity and predictive values were studied., Results: The ADFACS had a high internal consistency (α = 0.95). Three cutoff points of 1, 4, and 17 were provided to separate CS and MCI patients, MCI and mild AD patients, and mild AD and moderate AD patients, respectively. The ADFACS strongly correlated with functional (IDDD, 0.927) and cognitive (MMSE, 0.747) measures. A similar pattern of dysfunction, but in different grades, was found for the MCI and AD groups., Conclusion: The ADFACS is a reliable, valid, and sensitive instrument to assess functional abilities; it is useful in dementia assessment for elderly populations.

Mild cognitive impairment (MCI) is a transitional state between normal aging and Alzheimer disease (AD). Artificial neural networks (ANNs) are computational tools that can provide valuable support to clinical decision making, classification, and prediction of cognitive functioning. The aims of this study were to develop, train, and explore and develop the ability of ANNs to differentiate MCI and AD, and to study the relevant variables in MCI and AD diagnosis. The sample consisted of 346 controls and 79 MCI and 97 AD patients. A linear discriminant analysis (LDA) and ANNs with 12 input neurons (10 subtests of a neuropsychological test, the abbreviated Barcelona Test; age; and education), 4 hidden neurons, and output neuron (diagnosis) were used to classify the patients. The ANNs were superior to LDA in its ability to classify correctly patients (100-98.33% vs. 96.4-80%, respectively) and showed better predictive performance. Semantic fluency, working and episodic memory and education showed up as the most significant and sensitive variables for classification. Our results indicate that ANNs have an excellent capacity to discriminate MCI and AD patients from healthy controls. These findings provide evidence that ANNs can be a useful tool for the analysis of neuropsychological profiles related to clinical syndromes.

Investigate how the subventricular proliferation and organisation is modified in a patient with FTLD-ALS. We studied the subventricular zone (SVZ) of a patient with FTLD-ALS immunohistochemical and histologically. We found an increase of Ki-67 positive cells and neuroblast in the subventricular zone, suggesting an activation of proliferating activity in response to FTD-ALS. This proliferation can act as a compensatory mechanism for rapid neuronal death and its modulation could provide a new therapeutic pathway in ALS. These results suggest a modification of neurogenesis in FTD-ALS., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The abbreviated Barcelona Test (a-BT) is an instrument widely used in Spain and Latin American countries for general neuropsychological assessment. The purpose of the present study was to provide new norms for the a-BT as part of the Neuronorma project. The sample consisted of 346 healthy controls. Overlapping cell procedure and midpoint techniques were applied to develop the normative data. Age, education, and sex influences were studied. Results indicated that although age and education affected the score on this test, sex did not. Raw scores were transformed to age-adjusted scaled scores (SS(A)) based on percentile ranks. These SS(A) were also converted into age-education scaled scores using a linear regression model. Norms were presented on age-education scaled scores. Also, the a-BT cognitive profile was presented and should prove to be clinically useful for interpretation. These co-normed data will allow clinicians to compare scores from a-BT with all the tests included in the Neuronorma project.

Reelin is a glycoprotein that modulates synaptic function and plasticity in the mature brain, thereby favouring memory formation. We recently reported altered cerebral Reelin expression in Alzheimer's disease (AD). Here we demonstrate pronounced Reelin changes at protein and mRNA levels in the frontal cortex in adult Down's syndrome (DS), where the extra copy of chromosome 21 leads to overexpression of beta-amyloid. In cortical extracts of fetal DS samples we detected increased levels of the full-length Reelin and the 310-kDa fragment. Overexpression of mutant human amyloid precursor protein also led to an increase in levels of Reelin fragments in Tg2576 transgenic mice for human beta-amyloid. Finally, in vitro Abeta42 treatment of SH-SY5Y neuroblastoma cells led to increased Reelin levels. An altered pattern of Reelin glycosylation was detected in extracts from the frontal cortex of AD patients and in Abeta42-treated SH-SY5Y cells, supporting the notion that beta-amyloid triggers altered Reelin processing. These results provide evidence that Reelin expression and processing is altered in several amyloid conditions., (2009 Elsevier Inc. All rights reserved.)

Cortical representations of the native language and a second language may have different anatomical distribution. The relationships between the phonologic and orthographic forms of words continue to be debated. We present a bilingual patient whose competence in his mother tongue was disrupted following brain ischaemia. Semantic units were accessible only as isolated letters in written as well as oral language presentation. His second language appeared completely unaffected. Whole word system disturbance of both orthography and phonology pathways of the native language could explain this presentation. It is a great opportunity to learn about the language neural network when a bilingual subject presents with brain ischaemia.

This study forms part of the Spanish Multicenter Normative Studies (NEURONORMA project). Normative data for people aged over 49 years are presented for selected tasks of the visual object and space perception battery (VOSP) and for the judgment of line orientation (JLO) test. Age-adjusted norms were derived from a sample of 341 participants who are cognitively normal and community-dwelling. Age- and education-adjusted norms are also provided. Years of education were modeled on age-scaled scores to derive regression equations that were applied for further demographic adjustments. The normative information provided here should prove useful for characterizing and interpreting individual test performances as well as comparing the scores from these tests with any other test using NEURONORMA norms.

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.

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.

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 (Corsi's 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.

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.

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.

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.

Background: Variability of age at onset (AO) of Alzheimer disease (AD) among members of the same family is important as a biological clue and because of its clinical effects., Objective: To evaluate which clinical variables influence the discrepancy in AO among affected relatives with familial AD., Setting: Clinical genetic project of Spanish kindred with AD conducted by 4 academic hospitals in Madrid, Spain., Methods: Age at onset of AD in 162 families and discrepancy in AO in intragenerational and intergenerational affected pairs were analyzed in relation to age, sex, maternal or paternal transmission, pattern of inheritance, and apolipoprotein E genotype., Results: Maternal transmission of AD was significantly more frequent than paternal transmission (P < .001). In 27% of the affected individuals, AO occurred before the patient was 65 years old. Discrepancy in AO among siblings was within 5 years in 44% of the families, 6 to 10 years in 29%, and more than 10 years in 27% (range, 0-22). This discrepancy was independent of the sex of the sibling pairs and was significantly lower with maternal transmission of AD (P = .02). Segregation analysis showed no differences in the inheritance pattern between families with low (< or =5 years) or high (>5 years) AO discrepancy. Age at onset in carriers of the apolipoprotein E epsilon4 allele was slightly younger. However, among siblings, an extra apolipoprotein E epsilon4 allele was not consistently associated with earlier onset of AD. Eighty percent of patients, independent of sex or mode of transmission, were already affected at their parents' reported AO., Conclusions: There is a wide discrepancy in AO in affected siblings that is not clearly explained by a single clinical variable or apolipoprotein E genotype. The interaction of many factors probably determines AO in each affected individual. However, maternal transmission of AD seems to result in a similar AO in offspring, and the risk of developing dementia after the parent's reported AO decreases significantly.

Background: Available screening tests for dementia are of limited usefulness because they are influenced by the patient's culture and educational level. The Eurotest, an instrument based on the knowledge and handling of money, was designed to overcome these limitations. The objective of this study was to evaluate the diagnostic accuracy of the Eurotest in identifying dementia in customary clinical practice., Methods: A cross-sectional, multi-center, naturalistic phase II study was conducted. The Eurotest was administered to consecutive patients, older than 60 years, in general neurology clinics. The patients' condition was classified as dementia or no dementia according to DSM-IV diagnostic criteria. We calculated sensitivity (Sn), specificity (Sp) and area under the ROC curves (aROC) with 95% confidence intervals. The influence of social and educational factors on scores was evaluated with multiple linear regression analysis, and the influence of these factors on diagnostic accuracy was evaluated with logistic regression., Results: Sixteen neurologists recruited a total of 516 participants: 101 with dementia, 380 without dementia, and 35 who were excluded. Of the 481 participants who took the Eurotest, 38.7% were totally or functionally illiterate and 45.5% had received no formal education. Mean time needed to administer the test was 8.2+/-2.0 minutes. The best cut-off point was 20/21, with Sn = 0.91 (0.84-0.96), Sp = 0.82 (0.77-0.85), and aROC = 0.93 (0.91-0.95). Neither the scores on the Eurotest nor its diagnostic accuracy were influenced by social or educational factors., Conclusion: This naturalistic and pragmatic study shows that the Eurotest is a rapid, simple and useful screening instrument, which is free from educational influences, and has appropriate internal and external validity.

Aim: To review the current state of the art in neurotransmission in Alzheimer's disease (AD) and its involvement in the pathophysiology of the disease., Introduction: AD is a neurodegenerative disorder that is estimated to affect 15 million people around the world. Since the cholinergic hypothesis of AD was put forward 20 years ago, numerous studies have been conducted in an attempt to determine the role that neurotransmitters play in AD. Among other things, this has made it possible to develop drugs based on the inhibition of acetylcholinesterase., Development: The monoaminergic neurotransmission systems are examined, with special attention given to the cholinergic system, and their anatomical distribution, function, receptors, activity and degradation systems are also described. Peptidergic neurotransmission systems are only briefly discussed, since they are not the main objective of this report. We also review the cholinergic hypothesis and the possible interrelations between cholinergic neurotransmission and beta-amyloid metabolism, as well as the potential involvement of acetylcholinesterase inhibitor drugs in more fundamental pathophysiological mechanisms, which act with a neuroprotective component.

Changes in the glycosylation pattern of brain proteins have been associated with Creutzfeldt-Jakob disease (CJD). We have investigated the glycosylation status of acetylcholinesterase (AChE) by lectin binding assay. Our data show that in lumbar CSF from definite and probable sporadic CJD cases AChE activity is lower compared with that in age-matched controls. We also show, for the first time, that AChE glycosylation is altered in CJD CSF and brain. Unlike Alzheimer's disease, in which an alteration in both the glycosylation and levels of AChE molecular forms is observed, the abnormal glycosylation of AChE in CJD appears to be unrelated to changes in molecular forms of this enzyme. These findings suggest that altered AChE glycosylation in CJD may be a consequence of the general perturbation of the glycosylation machinery that affects prion protein, as well as other proteins. The diagnostic potential of these changes remains to be explored.

Introduction: The diagnosis of patients with cognitive deterioration or dementia requires a global approach in which the neuropsychological examination is a key piece. As part of the GERMCIDE study (Group for the Study and Multicenter Registry of Incident Cases of Dementia in Spain), a protocol was designed that included an assessment of the different cognitive functions that are most frequently altered in dementias (memory, orientation, speech, praxis, abstraction capacity and executive function)., Methods: In order to obtain data in normal subjects, this neuropsychological protocol was applied to a group of persons over 50 years without cognitive deterioration or dementia., Results: A total of 103 subjects whose ages ranged from 50 to 95 years (mean: 73.5; SD: 9.3 years); 39 (37.9%) men and 64 (62.1%) women were studied. The mean score on the Mini-Mental State Examination (MMSE) was 27/30 (SD: 2.0). In the speech and praxis tests, 90% of the subjects obtained the maximum value, while performances were more unequal in memory, reasoning and programming. Mean score, standard deviation and distribution in percentages for each subtest are presented., Conclusions: The values obtained in this sample of normal subjects and their distribution in percentages may be very helpful to facilitate the interpretation of the findings of the neuropsychological examination with the GERMCIDE protocol in the general neurology clinic visits and also in the specialized visits in dementia.

In this report, we present the clinical and pathological details of a kindred of four individuals with a novel missense mutation (V272A) of the presenilin 1 gene (PSEN1) that experienced a subcortical dementia. The age of onset of symptoms ranged 26-36-year old, with an age at death of 36-46 years. Initial symptom was a marked mood disorder, with prominent parkinsonism in one case. The neuropsychological study, as well as the neuroimaging and PET in the proband were concordant with a subcortical dementia. The cerebral pathology showed in this patient, aside from the classical lesions of Alzheimer disease, Lewy bodies in cortex and substantia nigra, and widespread subcortical neuritic lesions. This clinical pattern and pathology expands the clinical spectrum of familial Alzheimer's disease and compel to include mutations of PSEN1 gene in the genetic study of subcortical dementia.

A number of biomarkers (e.g. Abeta, tau) has been identified in Alzheimer's disease CSF. However, none fulfils the criteria of sensitivity and specificity (> 80%) needed for the development of an accurate diagnostic test. The lack of a suitable marker has prompted the search for new CSF biomarkers. In this study, the glycosylation of CSF proteins was examined using lectin blotting. Lumbar CSF was collected ante mortem from 22 non-Alzheimer's disease and 12 probable Alzheimer's disease cases and ventricular CSF collected post mortem from 7 non-Alzheimer's disease and 16 Alzheimer's disease cases confirmed by pathologic examination. When CSF glycoproteins were stained with wheat germ agglutinin (WGA), the staining intensity was found to be significantly lower in the Alzheimer's disease group. No difference in staining was found using other lectins (Canavalia ensiformis agglutinin, Ricinus communis agglutinin, Lens culinaris agglutinin). The measurement of WGA-reactive glycoproteins in CSF may be a useful biomarker for diagnosis of Alzheimer's disease.

As clinical diagnosis of Alzheimer's disease is only 80%-90% accurate, there is a need to identify biochemical markers of Alzheimer's disease. Previous studies have shown an abnormality in the glycosylation of acetylcholinesterase (AChE) in the CSF collected postmortem from patients with Alzheimer's disease. This abnormality was very specific for Alzheimer's disease, as it was not detected in other illnesses causing dementia. We report here that the glycosylation of AChE is also altered in lumbar CSF collected antemortem. The altered glycosylation was due to increased concentrations of a minor AChE isoform that does not bind to concanavalin A (Con A). Glycosylation of AChE may eventually be of diagnostic value, especially when used in combination with other CSF markers.

We studied the validity of a complete (S-IQCODE) and a shortened (SS- IQCODE) Spanish version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia in a clinical setting. Fifty-three consecutive outpatients were assessed with an extensive workup and followed up for 6 months in a specialized clinic for the diagnosis and management of dementia. Thirty eight (71%) were finally diagnosed as demented. The Mini-Mental State Examination (MMSE) had a slightly greater diagnostic power than did the S-IQCODE and the SS-IQCODE (sensitivity 89% vs. 84% and 79%; specificity 80% vs. 73% for both; positive predictive value 92% vs. 89% and 88%; negative predictive value 75% vs. 65% and 58%), but without statistical significance. Both the S-IQCODE and SS-IQCODE were independent of previous education of the patients. The best diagnostic results were obtained when the cognitive scores of the patient in the MMSE and the report of the relative in the S-IQCODE were simultaneously considered. We conclude that the IQCODE, in a complete as well as in a shortened form, is a good diagnostic instrument in the clinical setting that can enhance the validity of other cognitive tests.

Oxidative polymorphism of debrisoquine has been studied in patients suffering from many spontaneous disorders which show genetic and/or environmental factors in their pathogenesis. To elucidate whether any relationship exists between this genetic polymorphism and the risk of developing Alzheimer disease (AD) we determined the oxidative phenotype and metabolic ratio (MR) of debrisoquine (DBQ) in 47 patients with AD or senile dementia of Alzheimer type (SDAT) and 837 healthy controls. The patients were free of drugs during at least the previous 30 days; all the controls were free of drugs. Three patients (6.38%) and 42 controls (5.02%) were classified as poor metabolizers (PM) of DBQ (non-significant difference). The distribution of MR values in the AD/SDAT patients showed non-significant differences when compared with controls. There was no relation between oxidative polymorphism of DBQ and age at onset of the disease. These results suggest that DBQ oxidative genetic polymorphism cannot be considered as a risk factor for developing AD-SDAT.

Objectives: To elucidate whether any relationship exists between genetic acetylator polymorphism and the risk of developing Alzheimer's disease., Methods: Acetylator polymorphism has been determined, using sulphamethazine, in 54 patients with Alzheimer's disease or senile dementia of Alzheimer type and in 93 age-matched controls., Results: Thirty-one patients (57.4%) and 54 controls (58%) were classified as slow acetylators (non-significant difference). No relation was found between acetylator polymorphism and age at onset of disease and scores of Minimental examination and Blessed, Tomlinson & Roth scale in the group of patients with Alzheimer's disease/senile dementia of Alzheimer type., Conclusions: Our results do not support the existence of any relationship between acetylator polymorphism and the risk of developing Alzheimer type dementia.

We report a family with branchial myoclonus, spastic paraparesis, and cerebellar ataxia in which six members were affected in two generations and the inheritance appeared to be autosomal dominant. Age at onset ranged from 40 to 50 years. Rhythmic myoclonus involving the palate, pharynx, larynx, and face was followed by truncal ataxia and spastic paraparesis in most patients. CT and MRI revealed mild atrophy of the cerebral and cerebellar cortex and severe atrophy of the medulla and spinal cord. The pons appeared normal and the olives not hypertrophic. CSF studies revealed severe reduction of the serotonin metabolite 5-hydroxyindoleacetic acid. Treatment with 5-hydroxytryptophan and carbidopa at highest tolerated dose mildly improved ataxia but did not modify the myoclonus. Treatment with anticholinergics, benzodiazepines, phenytoin, valproate, carbamazepine, and baclofen was unsuccessful. The clinical symptoms were progressive, leading to death or severe disability 5 to 10 years after the onset of the disease.