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 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 Alzheimers disease). An empirical procedure was used to develop the shortened versions. All new versions demonstrated satisfactory internal consistency. Pearsons 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.
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 ?9-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.
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.
This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.
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.
Nonpharmacological therapies (NPTs) can improve the quality of life (QoL) of people with Alzheimers 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.
Hippocampal volume is reduced in Alzheimer Disease (AD) and has been proposed as a possible surrogate biomarker to aid early diagnosis. Whilst automated methods to segment the hippocampus from magnetic resonance images are available, manual segmentation, in spite of being time-consuming and unsuitable for large samples, is still the standard. In order to study the validity of FreeSurfers automated method, we compared hippocampal automated measures with manual tracing in a sample composed of healthy elderly (N=41), Mild Cognitive Impairment (MCI) (N=23), and AD (N=25) subjects. Percent volume overlap, percent volume difference, correlations, and Bland-Altman plots were studied. Automated measures were slightly larger than hand tracing ones (mean difference 10%). Percent volume overlap showed good results, but was far from perfect (78%). Manual and automated volume correlations were approximately 0.84 and the Bland-Altman analysis showed acceptable interchangeability of methods. Within-group analysis demonstrated that patient samples obtained smaller values in validity indexes than controls. Globally, FreeSurfers automated hippocampal volumetry showed adequate validity when compared to manual tracing, with a tendency to overestimation. Nevertheless, the greater difference between automated and manual segmentation in atrophic brains suggests that studies in AD based on this software could be more likely to produce false negatives.
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.
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.
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.
As part of the Spanish Multicenter Normative Studies (NEURONORMA project), we provide age- and education-adjusted norms for the following instruments: verbal span (digits), visuospatial span (Corsis test), letter-number sequencing (WAIS-III), trail making test, and symbol digit modalities test. The sample consists of 354 participants who are cognitively normal, community-dwelling, and age ranging from 50 to 90 years. Tables are provided to convert raw scores to age-adjusted scaled scores. These were further converted into education-adjusted scaled scores by applying regression-based adjustments. The current norms should provide clinically useful data for evaluating elderly Spanish people. These data may be of considerable use for comparisons with other normative studies. Limitations of these normative data are mainly related to the techniques of recruitment and stratification employed.
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 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.
Although memory deficits are typically the earliest and most profound symptoms of Alzheimers 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.
The expression of neurodegenerative diseases can be categorized into three main symptomatic domains: neurological, cognitive and, neuropsychiatric. This review focuses on the cognitive profile and neuropsychological assessment of Alzheimers disease (AD). The topography and progression of brain neuropathology determines the cognitive expression of the disease. Thus, in accordance with the initial involvement of the medial temporal lobe, cognitive changes in AD start with specific difficulties in encoding and storage of new information. This particular memory deficit can be optimally detected with memory tests that enhance mnemonic retrieval by means of encoding specificity technique such as the Free and Cued Selective Reminding Test (FCSRT). Along the course of the disease, the neuropathology spreads to association cortices, and other neuropsychological deficits can be detected. A comprehensive neuropsychological examination encompassing several cognitive domains can provide a pattern of altered and preserved functions that is helpful to early detection, differential diagnosis and even prognosis of progression in predementia stages. The use of adapted and standardized instruments is necessary to properly estimate cognitive and functional performance in AD.
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