Underdiagnosis of Unilateral Spatial Neglect in stroke unit.

OBJECTIVES: Unilateral spatial neglect (USN) is the incapacity to respond to stimuli presented opposite to a dysfunctional cerebral hemisphere. It is usually caused by non-dominant hemisphere lesions, leads to poorer prognosis and might be underdiagnosed. The objectives of the study were to ascertain the presence of USN in acute stroke patients and analyze the possible degree of underdiagnosis in a Stroke Unit. MATERIALS AND METHODS: Prospective study of consecutive non-dominant hemisphere stroke patients within a period of 21 months. "Line Bisection" and "Triangles Cancellation" tests were used for USN screening and "Circle Gap Detection Task" to confirm the USN. The results were compared with routine Stroke Unit assessment using the NIHSS to determine the possible degree of underdiagnosis. RESULTS: A total of 62 subjects, 38 women (61.29%), mean age of 74.05 (SD 10.5) years, were included. USN was diagnosed in 25 cases (40.3%) but 56% of them were not detected in routine evaluation using the NIHSS. CONCLUSIONS: Unilateral spatial neglect, a common cognitive deficit after acute stroke, is greatly underdiagnosed in routine Stroke Unit assessment. The use of simple USN-specific screening tools would improve diagnosis and therefore the possibility of implementing appropriate rehabilitation strategies.

Ischemic aetiology, self-reported frailty, and gender with respect to cognitive impairment in chronic heart failure patients.

BACKGROUND: Decisive information on the parameters involved in cognitive impairment in patients with chronic heart failure is as yet lacking. Our aim was to determine the functional and psychosocial variables related with cognitive impairment using the mini-mental-state examination (MMSE) with age-and education-corrected scores. METHODS: A cohort study of chronic heart failure patients included in an integrated multidisciplinary hospital/primary care program. The MMSE (corrected for age and education in the Spanish population) was administered at enrolment in the program. Analyses were performed in 525 patients. Demographic and clinical variables were collected. Comprehensive assessment included depression (Yesavage), family function (family APGAR), social network (Duke), dependence (Barthel Index), frailty (Barber), and comorbidities. Univariate and multivariate logistic regression were performed to determine the predictors of cognitive impairment. RESULTS: Cognitive impairment affected 145 patients (27.6 %). Explanatory factors were gender (OR: 2.77 (1.75-4.39) p < 0.001), ischemic etiology (OR: 1.99 (1.25-3.17) p = 0.004), frailty (OR: 1.58 (0.99 to 2.50, p =0.050), albumin > 3.5 (OR: 0.59 (0.35-0.99) p = 0.048), and beta-blocker treatment (OR: 0.36 (0.17 to 0.76, p = 0.007)). No association was found between cognitive impairment and social support or family function. CONCLUSION: The observed prevalence of cognitive impairment using MMSE corrected scores was 27.6 %. A global approach in the management of these patients is needed, especially focusing on women and patients with frailty, low albumin levels, and ischemic aetiology heart failure.

Updating functional brain units: Insights far beyond Luria.

This paper reviews Luria's model of the three functional units of the brain. To meet this objective, several issues were reviewed: the theory of functional systems and the contributions of phylogenesis and embryogenesis to the brain's functional organization. This review revealed several facts. In the first place, the relationship/integration of basic homeostatic needs with complex forms of behavior. Secondly, the multi-scale hierarchical and distributed organization of the brain and interactions between cells and systems. Thirdly, the phylogenetic role of exaptation, especially in basal ganglia and cerebellum expansion. Finally, the tripartite embryogenetic organization of the brain: rhinic, limbic/paralimbic, and supralimbic zones. Obviously, these principles of brain organization are in contradiction with attempts to establish separate functional brain units. The proposed new model is made up of two large integrated complexes: a primordial-limbic complex (Luria's Unit I) and a telencephalic-cortical complex (Luria's Units II and III). As a result, five functional units were delineated: Unit I. Primordial or preferential (brainstem), for life-support, behavioral modulation, and waking regulation; Unit II. Limbic and paralimbic systems, for emotions and hedonic evaluation (danger and relevance detection and contribution to reward/motivational processing) and the creation of cognitive maps (contextual memory, navigation, and generativity [imagination]); Unit III. Telencephalic-cortical, for sensorimotor and cognitive processing (gnosis, praxis, language, calculation, etc.), semantic and episodic (contextual) memory processing, and multimodal conscious agency; Unit IV. Basal ganglia systems, for behavior selection and reinforcement (reward-oriented behavior); Unit V. Cerebellar systems, for the prediction/anticipation (orthometric supervision) of the outcome of an action. The proposed brain units are nothing more than abstractions within the brain's simultaneous and distributed physiological processes. As function transcends anatomy, the model necessarily involves transition and overlap between structures. Beyond the classic approaches, this review includes information on recent systemic perspectives on functional brain organization. The limitations of this review are discussed.

Neuropsychological Assessment for Early Detection and Diagnosis of Dementia: Current Knowledge and New Insights.

Dementia remains an underdiagnosed syndrome, and there is a need to improve the early detection of cognitive decline. This narrative review examines the role of neuropsychological assessment in the characterization of cognitive changes associated with dementia syndrome at different states. The first section describes the early indicators of cognitive decline and the major barriers to their identification. Further, the optimal cognitive screening conditions and the most widely accepted tests are described. The second section analyzes the main differences in cognitive performance between Alzheimer's disease and other subtypes of dementia. Finally, the current challenges of neuropsychological assessment in aging/dementia and future approaches are discussed. Essentially, we find that current research is beginning to uncover early cognitive changes that precede dementia, while continuing to improve and refine the differential diagnosis of neurodegenerative disorders that cause dementia. However, neuropsychology faces several barriers, including the cultural diversity of the populations, a limited implementation in public health systems, and the adaptation to technological advances. Nowadays, neuropsychological assessment plays a fundamental role in characterizing cognitive decline in the different stages of dementia, but more efforts are needed to develop harmonized procedures that facilitate its use in different clinical contexts and research protocols.

NEURONORMA Cognitive Battery Associations with Cerebrospinal Fluid Amyloid-ß and Tau Levels in the Continuum of Alzheimer's Disease.

BACKGROUND: Neuropsychological assessments are essential to define the cognitive profile and contribute to the diagnosis of Alzheimer's disease (AD). The progress in knowledge about the pathophysiological process of the disease has allowed conceptualizing AD through biomarkers as a biological continuum that encompasses different clinical stages. OBJECTIVE: To explore the association between cerebrospinal fluid (CSF) biomarkers of AD and cognition using the NEURONORMA battery, in a sample of cognitively unimpaired (CU), mild cognitive impaired (MCI), and mild dementia of the Alzheimer type (DAT) subjects, and to characterize the cognitive profiles in MCI subjects classified by A/T/N system. METHODS: 42 CU, 35 MCI, and 35 mild DAT were assessed using the NEURONORMA battery. Core AD biomarkers [amyloid-ß42 (Aß42) peptide, total tau (t-tau), and phosphorylated tau 181 (p-tau181)] proteins were measured in CSF. Correlation coefficients, multivariate regression, and effect sizes were calculated. We explored the age- and education-adjusted cognitive profiles by A/T/N variants within the MCI group. RESULTS: Cognitive outcomes were directly associated with CSF Aß42 and inversely with CSF tau measures. We found differences in both biomarkers and cognitive outcomes comparing all pairs except for CSF measures between cognitively impaired groups. The highest effect size was in memory tasks and biomarkers ratios. Lower performances were in memory and executive domains in MCI subjects with AD pathology (A+T+N±) compared to those with normal levels of AD biomarkers (A- T- N). CONCLUSION: This study provides further evidence of the validity of Spanish NEURONORMA cognitive battery to characterize cognitive impairment in the AD pathological continuum.

Nonpharmacological therapies in Alzheimer's disease: a systematic review of efficacy.

INTRODUCTION: Nonpharmacological therapies (NPTs) can improve the quality of life (QoL) of people with Alzheimer's disease (AD) and their carers. The objective of this study was to evaluate the best evidence on the effects of NPTs in AD and related disorders (ADRD) by performing a systematic review and meta-analysis of the entire field. METHODS: Existing reviews and major electronic databases were searched for randomized controlled trials (RCTs). The deadline for study inclusion was September 15, 2008. Intervention categories and outcome domains were predefined by consensus. Two researchers working together detected 1,313 candidate studies of which 179 RCTs belonging to 26 intervention categories were selected. Cognitive deterioration had to be documented in all participants, and degenerative etiology (indicating dementia) had to be present or presumed in at least 80% of the subjects. Evidence tables, meta-analysis and summaries of results were elaborated by the first author and reviewed by author subgroups. Methods for rating level of evidence and grading practice recommendations were adapted from the Oxford Center for Evidence-Based Medicine. RESULTS: Grade A treatment recommendation was achieved for institutionalization delay (multicomponent interventions for the caregiver, CG). Grade B recommendation was reached for the person with dementia (PWD) for: improvement in cognition (cognitive training, cognitive stimulation, multicomponent interventions for the PWD); activities of daily living (ADL) (ADL training, multicomponent interventions for the PWD); behavior (cognitive stimulation, multicomponent interventions for the PWD, behavioral interventions, professional CG training); mood (multicomponent interventions for the PWD); QoL (multicomponent interventions for PWD and CG) and restraint prevention (professional CG training); for the CG, grade B was also reached for: CG mood (CG education, CG support, multicomponent interventions for the CG); CG psychological well-being (cognitive stimulation, multicomponent interventions for the CG); CG QoL (multicomponent interventions for PWD and CG). CONCLUSION: NPTs emerge as a useful, versatile and potentially cost-effective approach to improve outcomes and QoL in ADRD for both the PWD and CG.

Medial temporal lobe correlates of memory screening measures in normal aging, MCI, and AD.

UNLABELLED: This article aimed to study the correlations for both the Memory Impairment Screen (MIS) and the Free and Cued Selective Reminding Test (FCSRT) with regard to the volumetric measures of hippocampal formation and entorhinal cortex and to explore the effect size of these measures. METHODS: A total of 34 healthy controls, 24 participants with mild cognitive impairment (MCI), and 20 mild-to-moderate-staged Alzheimer disease (AD) participants underwent neuropsychological testing and magnetic resonance imaging (MRI). Global volumetric measures were obtained and hippocampal and entorhinal volumes were calculated. Spearman correlations were calculated between memory scores and brain volumes and an effect size analysis was performed. RESULTS: No significant correlations with global brain volumes were found. There were dissimilar correlations among groups regarding memory and hippocampal and entorhinal volumes. No significant relationships were observed in healthy controls. The MCI group reached the higher correlation indexes, up to r = .55. In AD, only one significant correlation was observed between the delayed score of the FCSRT and the left hippocampus. Effect size values were higher for memory tests than for MRI measures, reaching d = 4.3 for the delayed score of the FCSRT. CONCLUSIONS: Although the MIS did not reach the strong results of the FCSRT, it demonstrated a similar pattern to the FCSRT in correlational analysis. These results support the validity and usefulness of the MIS despite its brevity of application. Memory testing showed better discrimination among healthy controls, MCI, and AD participants than MRI measures by means of effect size analysis.

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 FreeSurfer's 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, FreeSurfer's 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.

Validation of the Neuronorma battery for neuropsychological assessment in multiple sclerosis.

BACKGROUND: Cognitive dysfunction is prevalent among patients with multiple sclerosis (MS). In recent years, several (generally brief) neuropsychological batteries have been proposed for cognitive assessment. There is a need for comprehensive batteries providing complete cognitive assessment of patients with MS. The Neuronorma battery includes several standardised neuropsychological tests examining the main cognitive domains, and is available in several countries. The aim of this study was to validate the battery for cognitive assessment in a sample of patients with MS and healthy controls, and to find the most appropriate criteria for defining cognitive impairment using this battery. METHODS: Five hundred and sixty participants (280 with MS and 280 controls matched for age, sex, and years of education) were included. Inter-group differences were calculated using the Mann-Whitney U test and effect sizes with Cohen's d. Several criteria for definition of cognitive impairment were evaluated, according to different cut-off points, and the number of tests and cognitive domains impaired. Receiver operating characteristic curves with 95% confidence intervals were estimated and they were compared using the DeLong method. RESULTS: Patients with MS showed poorer performance in almost all cognitive tests, with large effect sizes for the Symbol Digit Modalities Test and Judgement of Line Orientation, and moderate effects for Digit Span Backward, the Corsi test, Trail Making Test, Free and Cued Selective Reminding Test, Rey-Osterrieth Complex Figure (recall), verbal fluency (P words), and the Stroop Color-Word Interference Test. The area under the curve was superior for classification by cognitive domain than for the mean scaled score of the tests or the number of tests showing impairment according to different cut-off points for the adjusted scaled scores. CONCLUSIONS: Our study validates the Neuronorma battery for cognitive assessment of patients with MS. The battery is currently available in several countries with reliable normative data, and may be useful in both the clinical and the research settings when comprehensive neuropsychological examination is warranted.

Ecological assessment of executive functions in mild cognitive impairment and mild Alzheimer's disease.

Although memory deficits are typically the earliest and most profound symptoms of Alzheimer's disease (AD) and mild cognitive impairment (MCI), there is increasing recognition of subtle executive dysfunctions in these patients. The purpose of the present study was to determine the sensitivity of the Behavioral Assessment of the Dysexecutive Syndrome (BADS), and to detect early specific signs of the dysexecutive syndrome in the transition from normal cognition to dementia. The BADS was administered to 50 MCI subjects, 50 mild AD patients, and 50 normal controls. Statistically significant differences were found among the three groups with the AD patients performing most poorly, and the MCI subjects performing between controls and AD patients. The Rule Shift Cards and the Action Program subtests were the most highly discriminative between MCI and controls; the Zoo Map and Modified Six Elements between MCI and AD; and the Action Program, Zoo Map, and Modified Six Elements between AD and controls. These results demonstrate that the BADS is clinically useful in discriminating between normal cognition and progressive neurodegenerative conditions. Furthermore, these data confirm the presence of a dysexecutive syndrome even in mildly impaired elderly subjects.

Visual search in unilateral spatial neglect: The effects of distractors on a dynamic visual search task.

The objective of this study was to examine visual scanning performance in patients with Unilateral Spatial Neglect (USN) in a visual search task. Thirty-one right hemisphere stroke patients with USN were recruited. They performed a dynamic visual search task with two conditions, with and without distractors, while eye movements were monitored with an eye-tracker. The main goal of the task was to select target stimuli that appeared from the top of the screen and moved vertically downward. Target detection and visual scanning percentage were assessed over two hemispaces (right, left) on two conditions (distractor, no distractor). Most Scanned Regions (MSR) were calculated to analyze the areas of the screen where most points of fixation were directed to. Higher target detection rate and visual scanning percentages were found on the right hemispace on both conditions. From the MSRs we found that participants with a center of attention further to the right of the screen also presented smaller overall MSRs. Right hemisphere stroke patients with USN presented not only a significant rightward bias but reduced overall search areas, implying hyperattention does not only restrict search on the horizontal (right-left) axis but the vertical axis (top-bottom) too.

Auditory event-related potentials (P3) and cognitive performance in recreational ecstasy polydrug users: evidence from a 12-month longitudinal study.

RATIONALE: There is important preclinical evidence of the long-lasting neurotoxic and selective effects of ecstasy (MDMA) on serotonin systems in nonhuman primates. In humans, long-term recreational use of ecstasy has been mainly associated with memory impairment. OBJECTIVE: The first aim of our study was to evaluate the cognitive and electrophysiological long-term alterations associated with lifetime ecstasy use within a sample of ecstasy polydrug users along a 1-year follow-up. Our second aim was to explore the relationship between specific cognitive functions and P300 (P3) event-related potentials (ERPs) in ecstasy users. MATERIALS AND METHODS: We conducted auditory P3 latency and amplitude and administered a battery of cognitive tests to three groups of subjects: 14 current ecstasy polydrug users, 13 current cannabis users, and 22 controls free of illicit drugs in two evaluations during 1 year. RESULTS: We found significant differences between ecstasy users and controls on cognitive measures of word fluency, processing speed, and memory recognition after 1-year follow-up. We found no significant differences between ecstasy and cannabis users or cannabis users and controls on cognitive tests. Lifetime ecstasy use was associated with poorer memory recognition. No group differences were shown on P3 latency or amplitude. Significant correlations emerged between P3 latency and cannabis lifetime use (higher cannabis use was related to faster latency, showing a paradoxical effect) but not with ecstasy exposure. CONCLUSIONS: Our findings provide evidence of mild long-term cognitive deficits among ecstasy polydrug users. Both ecstasy use and the dynamic interaction between ecstasy and cannabis effects may account for these deficits. No significant P3 alterations were found in ecstasy users.

A preliminary study of the mini-mental state examination in a Spanish child population.

The Mini-Mental State Examination is one of the most widely used screening tests for the adult population in daily neurologic practice. The aim of this study was to describe and to analyze the results of the Mini-Mental State Examination administered to Spanish children and to assess the relationship between Mini-Mental State Examination scores and the child's mental age/intelligence quotient. The study population included 181 children whose ages ranged between 4 and 12 years. The neuropsychologic battery consisted of the Mini-Mental State Examination and Kaufman Brief Intelligence Test. Percentiles were obtained for the Mini-Mental State Examination total score according to age ranges. Performance gradually increased from 4 to 10 years of age when a plateau in the total Mini-Mental State Examination score was reached. At the age of 6 years, results exceeded 24 on average. Pairwise mean comparisons showed statistically significant differences between the age groups (P < .05). Data distribution could be classified in 4 independent groups for the following chronologic ages: 4, 5, and 6 years and from 7 to 12 years of age. The total Mini-Mental State Examination score correlated significantly with the child's chronologic (r = 0.80, P < .001) and mental (r = 0.76, P < .001) ages. This is a preliminary study of the application of the Mini-Mental State Examination in a Spanish child population as well as a first step for the assessment of the usefulness of this instrument as a cognitive screening tool for children's development.

The Memory Binding Test: Development of Two Alternate Forms into Spanish and Catalan.

BACKGROUND: The Memory Binding Test (MBT) is emerging as a promising tool for the detection of subtle memory impairment suggestive of Alzheimer's disease (AD). For such a test to be widely accessed and used, the availability of both alternate forms and language adaptations is required. OBJECTIVES: To develop a thorough methodology for obtaining alternate forms (A and B) of the MBT in Spanish and Catalan and to assess their equivalence. METHOD: According to the original development of the test, frequency was taken as the lexical variable of reference for the Spanish and Catalan adaptations. A crossed design protocol by form and language was used to compare the MBT results in a sample of 290 cognitively normal middle-aged participants. Pairwise Intraclass Correlation Coefficients (ICCs) were calculated among the six possible combinations. RESULTS: The Spanish and Catalan lists of words for the MBT A and B resulting from the adaptation process as well as the original lists in English are presented. ICC indices for the comparisons between forms and languages ranged from 0.56 to 0.82. CONCLUSION: The MBT A and B in Spanish and Catalan showed similar outcomes and can be considered equivalent. Moreover, the thorough methodology presented here for the transcultural adaptation and equivalence study, could serve as a model for future adaptations of the MBT and other verbal tests.

Psychometric Properties of the Memory Binding Test: Test-Retest Reliability and Convergent Validity.

BACKGROUND: Episodic memory testing is fundamental for the diagnosis of Alzheimer's disease (AD). Although the Free and Cued Selective Reminding Test (FCSRT) is widely used for this purpose, it may not be sensitive enough for early detection of subtle decline in preclinical AD. The Memory Binding Test (MBT) intends to overcome this limitation. OBJECTIVES: To analyze the test-retest reliability of the MBT and its convergent validity with the FCRST. METHODS: 36 cognitively healthy participants of the ALFA Study, aged 45 to 65, were included for the test-retest study and 69 for the convergent analysis. They were visited twice in a period of 6 ± 2 weeks. Test-retest reliability was determined by the calculation of the intra-class correlation coefficient (ICC). Score differences were studied by computing the mean percentage of score variation between visits and visualized by Bland-Altman plots. Convergent validity was determined by Pearson's correlations. RESULTS: ICC values in the test-retest reliability analysis of the MBT direct scores ranged from 0.64 to 0.76. Subjects showed consistent practice effects, with mean amounts of score increasing between 10% and 26%. Pearson correlation between MBT and FCSRT direct scores showed r values between 0.40 and 0.53. The FCSRT displayed ceiling effects not observed in the MBT. CONCLUSIONS: The MBT shows adequate test-retest reliability and overall moderate convergent validity with the FCSRT. Unlike the FCSRT, the MBT does not have ceiling effects and it may therefore be especially useful in longitudinal studies, facilitating the measurement of subtle memory performance decline and the detection of very early AD.

One-Year Reference Norms of Cognitive Change in Spanish Old Adults: Data from the NEURONORMA Sample.

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.

[What is hidden behind the Baking Tray Task? Study of sensibility and specificity in right-hemispheric stroke patients]. / Que se esconde tras el Baking Tray Task? Estudio de sensibilidad y especificidad en sujetos con ictus hemisferico derecho.

INTRODUCTION: Tham and Tegner proposed the Baking Tray Task (BTT) as a fast simple assessment test for detecting spatial negligence. However, very few studies have examined its validity as a diagnostic test. AIM: To analyse the diagnostic validity of the BTT by measuring its specificity and sensitivity in a sample of subjects with right hemisphere strokes. SUBJECTS AND METHODS: Forty-eight patients with right hemisphere vascular lesions were distributed in two groups (negligence group, n = 35; non-negligence group, n = 13) according to the scores obtained in a battery of visuospatial examination tests. The participants' performance on the BTT was compared with that of a healthy control group (n = 12). RESULTS: The results showed a high level of sensitivity of the BTT, but low specificity. The performance on the BTT of eight of the 13 members of the non-negligence group was suggestive of negligence. CONCLUSIONS: The BTT has proved to be a sensitive test for the detection of spatial negligence. Yet, based on its low specificity, its use alone as a single diagnostic test is not recommended.

TITLE: Que se esconde tras el Baking Tray Task? Estudio de sensibilidad y especificidad en sujetos con ictus hemisferico derecho.Introduccion. Tham y Tegner propusieron el Baking Tray Task (BTT) como una prueba de evaluacion rapida y simple para la deteccion de negligencia espacial. No obstante, apenas existen estudios que hayan examinado su validez como prueba diagnostica. Objetivo. Analizar la validez diagnostica del BTT, midiendo su especificidad y sensibilidad, en una muestra de sujetos con ictus hemisfericos derechos. Sujetos y metodos. Cuarenta y ocho pacientes con lesiones vasculares hemisfericas derechas distribuidos en dos grupos (grupo negligencia, n = 35; grupo no negligencia, n = 13) en funcion de las puntuaciones obtenidas en una bateria de exploracion visuoespacial. La ejecucion de los participantes en el BTT se comparo con un grupo control sano (n = 12). Resultados. Los resultados mostraron una alta sensibilidad del BTT, pero una baja especificidad. Ocho de los 13 integrantes del grupo no negligencia obtuvieron un rendimiento en el BTT sugestivo de negligencia. Conclusiones. El BTT se muestra como un test sensible para la deteccion de la negligencia espacial. Sin embargo, basandonos en su baja especificidad, no es recomendable su uso aislado como prueba unica de diagnostico.

Reference Data of the Spanish Memory Binding Test in a Midlife Population from the ALFA STUDY (Alzheimer's and Family).

BACKGROUND: The Memory Binding Test (MBT) is a novel test based on the learning of two lists of words, developed to detect early memory impairment suggestive of Alzheimer's disease (AD). OBJECTIVE: To present and provide reference data of the Spanish MBT in a midlife population of mainly first-degree descendants of AD patients. METHODS: 472 cognitively unimpaired subjects, aged 45 to 65 and participants of the ALFA STUDY, were included. Raw scores were transformed to scaled scores on which multivariate regression analysis was applied adjusting by age, gender, and education level. A standard linear regression was employed to derive the scaled score adjusted. Sociodemographic corrections were applied and an adjustment table was constructed. RESULTS: Performance was heterogeneously influenced by sociodemographic factors. Age negatively influenced free recall. Education tends to have an influence in the results showing lower performance with lower education level. Women tend to outperform men in the learning of the first list and total recall. Only a few variables were unaffected by sociodemographic factors such as those related to semantic proactive interference (SPI) and to the retention of learned material. Our results point out that some vulnerability to SPI is expectable in cognitively healthy subjects. Close to 100% of the learned material was maintained across the delay interval. CONCLUSION: This study contributes with reference data for the MBT providing the necessary adjustments for sociodemographic characteristics. Our data may prove to be useful for detecting asymptomatic at-risk candidates for secondary prevention studies of AD.

A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials.

The recent prospect of pharmaceutical interventions for cognitive impairment of Down syndrome (DS) has boosted a number of clinical trials in this population. However, running the trials has raised some methodological challenges and questioned the prevailing methodology used to evaluate cognitive functioning of DS individuals. This is usually achieved by comparing DS individuals to matched healthy controls of the same mental age. We propose a new tool, the TESDAD Battery that uses comparison with age-matched typically developed adults. This is an advantageous method for probing the clinical efficacy of DS therapies, allowing the interpretation and prediction of functional outcomes in clinical trials. In our DS population the TESDAD battery permitted a quantitative assessment of cognitive defects, which indicated language dysfunction and deficits in executive function, as the most important contributors to other cognitive and adaptive behavior outcomes as predictors of functional change in DS. Concretely, auditory comprehension and functional academics showed the highest potential as end-point measures of therapeutic intervention for clinical trials: the former as a cognitive key target for therapeutic intervention, and the latter as a primary functional outcome measure of clinical efficacy. Our results also emphasize the need to explore the modulating effects of IQ, gender and age on cognitive enhancing treatments. Noticeably, women performed significantly better than men of the same age and IQ in most cognitive tests, with the most consistent differences occurring in memory and executive functioning and negative trends rarely emerged on quality of life linked to the effect of age after adjusting for IQ and gender. In sum, the TESDAD battery is a useful neurocognitive tool for probing the clinical efficacy of experimental therapies in interventional studies in the DS population suggesting that age-matched controls are advantageous for determining normalization of DS.

Cognitive-motor intervention in Alzheimer's disease: long-term results from the Maria Wolff trial.

BACKGROUND: Little is known about the long-term acceptance and effects of cognitive and motor stimulation interventions (CMSI) in Alzheimer's disease (AD). OBJECTIVE: To evaluate a replicable CMSI program for mild cognitive impairment (MCI) and mild-to-moderate AD persons. METHODS: Eighty-four non-institutionalized subjects with AD were randomized to receive either CMSI, administered by a single care provider, or standard support. Cognition, activities of daily living (ADL), mood, and study partner's subjective burden were assessed by blinded raters. Data on institutionalization, psychiatric medications, and demise were collected by the study physicians. Random effects model and survival analyses were conducted, after 2 and 3 years of study. RESULTS: Three-year assessments could be performed by the physician in 85% and by the blinded rater in 66% of subjects. Significant benefits were observed in basic ADL at the 2- and 3-year assessments, whereas instrumental ADL showed benefits only up to the second year of intervention (p < 0.05). CONCLUSION: Long-term cognitive-motor stimulation is well accepted and produces functional benefits in subjects with AD, with no extra subjective burden in the partner.