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Although patients with Alzheimer disease (AD) share clinical and histological features regardless of age of onset, the hypothesis that early onset AD constitutes a distinct subgroup prevails. Some authors suggest that early attention or language impairment constitute patterns of differentiation in terms of neuropsychological profile, between these groups. However, investigations are not consensual in terms of cognitive domains affected in each group.
We examined the usefulness of brief neuropsychological tests and serum Aβ as a predictive test for detecting MCI/AD in older adults. Serum Aβ levels were measured from 208 subjects who were cognitively normal at enrollment and blood draw. Twenty-eight of the subjects subsequently developed MCI (n = 18) or AD (n = 10) over the follow-up period. Baseline measures of global cognition, memory, language fluency, and serum Aβ(1-42) and the ratio of serum Aβ(1-42)/Aβ(1-40) were significant predictors for future MCI/AD using Cox regression with demographic variables, APOE ε4, vascular risk factors, and specific medication as covariates. An optimal sensitivity of 85.2% and specificity of 86.5% for predicting MCI/AD was achieved using ROC analyses. Brief neuropsychological tests and measurements of Aβ(1-42) obtained via blood warrants further study as a practical and cost effective method for wide-scale screening for identifying older adults who may be at-risk for pathological cognitive decline.
An extensive battery of neuropsychological tests is currently used to classify individuals as healthy (HV), mild cognitively impaired (MCI), and with Alzheimer's disease (AD). We used machine learning models for effective cognitive impairment classification and optimized the number of tests for expeditious and inexpensive implementation.
Background: The aging process and declining estradiol levels are two important factors that cause structural brain alterations. Many prior studies have investigated these two elements and revealed controversial results in menopausal women. Here, a cross-sectional study was designed to individually evaluate estradiol-related structural changes in the brain. Methods: A total of 45 early menopausal women and 54 age-matched premenopausal controls were enrolled and subjected to magnetic resonance imaging (MRI) scans, blood biochemistry tests, and neuropsychological tests. MRI structural images were analyzed using FreeSurfer to detect changes in subcortical and cortical volumes as well as cortical thickness. Finally, structural brain data as well as clinical and neuropsychological data were used for Pearson's correlation analyses to individually determine estradiol-related structural and functional changes in the brains of early menopausal women. Results: Compared with the premenopausal controls, the early menopausal women showed significant subcortical volumetric loss in the left amygdala and right amygdala, higher serum follicle-stimulating hormone (FSH) levels, more recognizable climacteric and depressive symptoms, decreased quality of sleep, and decreased working memory and executive functions. Simultaneously, FSH levels were related to lower working memory accuracy and longer working memory reaction time. Decreased subcortical volume in the bilateral amygdala was also related to lower working memory accuracy and longer executive reaction time in early menopausal women. Conclusion: The data suggest that estradiol deficiency in early menopausal women can lead to subcortical volume and functional brain changes, which may contribute to further understanding the neurobiological role of declined estradiol levels in early menopausal women.
Ecological validity should be the cornerstone of any assessment of cognitive functioning. For this purpose, we have developed a preliminary study to test the Art Gallery Test (AGT) as an alternative to traditional neuropsychological testing. The AGT involves three visual search subtests displayed in a virtual reality (VR) art gallery, designed to assess visual attention within an ecologically valid setting. To evaluate the relation between AGT and standard neuropsychological assessment scales, data were collected on a normative sample of healthy adults (n = 30). The measures consisted of concurrent paper-and-pencil neuropsychological measures [Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), and Color Trails Test (CTT)] along with the outcomes from the three subtests of the AGT. The results showed significant correlations between the AGT subtests describing different visual search exercises strategies with global and specific cognitive measures. Comparative visual search was associated with attention and cognitive flexibility (CTT); whereas visual searches involving pictograms correlated with global cognitive function (MoCA).
Alzheimer's disease (AD) is a slowly progressing disease for which there is no known therapeutic cure at present. Ongoing research around the world is actively engaged in the quest for identifying markers that can help predict the future cognitive state of individuals so that measures can be taken to prevent the onset or arrest the progression of the disease. Researchers are interested in both biological and neuropsychological markers that can serve as good predictors of the future cognitive state of individuals. The goal of this study is to identify non-invasive, inexpensive markers and develop neural network models that learn the relationship between those markers and the future cognitive state. To that end, we use the renowned Alzheimer's Disease Neuroimaging Initiative (ADNI) data for a handful of neuropsychological tests to train Recurrent Neural Network (RNN) models to predict future neuropsychological test results and Multi-Level Perceptron (MLP) models to diagnose the future cognitive states of trial participants based on those predicted results. The results demonstrate that the predicted cognitive states match the actual cognitive states of ADNI test subjects with a high level of accuracy. Therefore, this novel two-step technique can serve as an effective tool for the prediction of Alzheimer's disease progression. The reliance of the results on inexpensive, non-invasive tests implies that this technique can be used in countries around the world including those with limited financial resources.
We investigated whether standardized neuropsychological tests and experimental cognitive paradigms measure the same cognitive faculties. Specifically, do neuropsychological tests commonly used to assess attention measure the same construct as attention paradigms used in cognitive psychology and neuroscience? We built on the "general attention factor", comprising several widely used experimental paradigms (Huang et al., 2012). Participants (n = 636) completed an on-line battery (TestMyBrain.org) of six experimental tests [Multiple Object Tracking, Flanker Interference, Visual Working Memory, Approximate Number Sense, Spatial Configuration Visual Search, and Gradual Onset Continuous Performance Task (Grad CPT)] and eight neuropsychological tests [Trail Making Test versions A & B (TMT-A, TMT-B), Digit Symbol Coding, Forward and Backward Digit Span, Letter Cancellation, Spatial Span, and Arithmetic]. Exploratory factor analysis in a subset of 357 participants identified a five-factor structure: (1) attentional capacity (Multiple Object Tracking, Visual Working Memory, Digit Symbol Coding, Spatial Span), (2) search (Visual Search, TMT-A, TMT-B, Letter Cancellation); (3) Digit Span; (4) Arithmetic; and (5) Sustained Attention (GradCPT). Confirmatory analysis in 279 held-out participants showed that this model fit better than competing models. A hierarchical model where a general cognitive factor was imposed above the five specific factors fit as well as the model without the general factor. We conclude that Digit Span and Arithmetic tests should not be classified as attention tests. Digit Symbol Coding and Spatial Span tap attentional capacity, while TMT-A, TMT-B, and Letter Cancellation tap search (or attention-shifting) ability. These five tests can be classified as attention tests.
Longitudinal measurement invariance analyses are an important way to assess a test's ability to estimate the underlying construct over time, ensuring that cognitive scores across visits represent a similar underlying construct, and that changes in test performance are attributable to individual change in cognitive abilities. We aimed to evaluate longitudinal measurement invariance in a large, social and culturally diverse sample over time.
In neuropsychology, fully immersive virtual reality (VR) has been spotlighted as a promising tool. It is considered that VR not only overcomes the existing limitation of neuropsychological tests but is also appropriate for treating executive functions (EFs) within activities of daily living (ADL) due to its high ecological validity. While fully immersive VR offers new possibilities of neuropsychological tests, there are few studies that overview the intellectual landscape and academic trends in the research related to mainly targeted EFs with fully immersive VR.
Two of the most commonly used methods to assess memory functioning in studies of cognitive aging and dementia are story memory and list learning tests. We hypothesized that the most commonly used story memory test, Wechsler's Logical Memory, would generate more pronounced practice effects than a well validated but less common list learning test, the Neuropsychological Assessment Battery (NAB) List Learning test. Two hundred eighty-seven older adults, ages 51 to 100 at baseline, completed both tests as part of a larger neuropsychological test battery on an annual basis. Up to five years of recall scores from participants who were diagnosed as cognitively normal (n = 96) or with mild cognitive impairment (MCI; n = 72) or Alzheimer's disease (AD; n = 121) at their most recent visit were analyzed with linear mixed effects regression to examine the interaction between the type of test and the number of times exposed to the test. Other variables, including age at baseline, sex, education, race, time (years) since baseline, and clinical diagnosis were also entered as fixed effects predictor variables. The results indicated that both tests produced significant practice effects in controls and MCI participants; in contrast, participants with AD declined or remained stable. However, for the delayed-but not the immediate-recall condition, Logical Memory generated more pronounced practice effects than NAB List Learning (b = 0.16, p < .01 for controls). These differential practice effects were moderated by clinical diagnosis, such that controls and MCI participants-but not participants with AD-improved more on Logical Memory delayed recall than on delayed NAB List Learning delayed recall over five annual assessments. Because the Logical Memory test is ubiquitous in cognitive aging and neurodegenerative disease research, its tendency to produce marked practice effects-especially on the delayed recall condition-suggests a threat to its validity as a measure of new learning, an essential construct for dementia diagnosis.
The Guatemalan pediatric population is affected by a high incidence of poverty and violence. The previous literature showed that these experiences may ultimately impact cognitive performance. The aim of this article is to update the standardized scores for ten neuropsychological tests commonly used in Guatemala considering vulnerability. A total of 347 healthy children and adolescents from 6 to 17 years of age (M = 10.83, SD = 3) were assessed, controlling for intelligence, mental health and neuropsychological history. The standard scores were created using multiple linear regression and standard deviations from residual values. The predictors included were the following: age, age squared (age2), mean parental education (MPE), mean parental education squared (MPE2), gender, and vulnerability, as well as their interaction. The vulnerability status was significant in the scores for language, attention and executive functions. To the best of our knowledge, this is the first study that includes the condition of vulnerability in the calculation of neuropsychological standard scores. The utility of this update is to help in the early detection of special needs in this disadvantaged population, promoting more accurate interventions in order to alleviate the negative effects that living in vulnerable conditions has on children and adolescents.
To study the ability of neuropsychological tests, manual MRI hippocampal volume measures, regional volume and cortical thickness measures to identify subjects with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy age-matched controls. Neuropsychological tests, manual hippocampal volume, automated regional volume and regional cortical thickness measures were performed in 120 AD patients, 120 MCI subjects, and 111 controls. The regional cortical thickness and volumes in MCI subjects were significantly decreased in limbic/paralimbic areas and temporal lobe compared to controls. Atrophy was much more extensive in the AD patients compared to MCI subjects and controls. The combination of neuropsychological tests and volumes revealed the highest accuracy (82% AD vs. MCI; 94% AD vs. control; 83% MCI vs. control). Adding regional cortical thicknesses into the discriminate analysis did not improve accuracy. We conclude that regional cortical thickness and volume measures provide a panoramic view of brain atrophy in AD and MCI subjects. A combination of neuropsychological tests and regional volumes are important when discriminating AD from healthy controls and MCI.
Novel tests of semantic memory (SM)-for example, memory for news events (NE; news facts) or famous personalities-are useful for estimating the severity of retrograde amnesia. Individuals with mild cognitive impairment exhibit relatively intact SM/language on traditional neuropsychological tests but exhibit consistent impairment on novel tests of SM, suggesting novel SM tests are dissimilar from traditional SM tests. To identify the relationship between NE memory and traditional cognitive measures, older adults (N = 51) completed a traditional neuropsychological battery and the Retrograde Memory News Events Test (RM-NET; a new test that robustly measures NE memory across the adult life span with high temporal resolution), and the relationship between performance on these tests was examined. Total RM-NET scores were more closely aligned with episodic memory scores than SM scores. The strength of the association between NE scores and episodic memory scores decreased as the age of NE memory increased. Tests of news events appear to reflect performance on traditional tests of episodic memory rather than SM, especially when recent news events are tested.
The neuropathological confirmation serves as the gold standard for diagnosing Alzheimer's disease (AD), but it is usually not available to the living individuals. In addition, the gold standard for diagnosing Mild Cognitive Impairment (MCI) remains unclear yet. Neuropsychological testing, such as the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), is commonly used tests in identifying AD and MCI, offering convenience, affordability, non-invasiveness, and accessibility in clinical settings. We aimed to accurately evaluate the discriminative ability of the three tests administrated at the same visit simultaneously in detecting AD and MCI due to AD in the absence of a gold standard.
Valproate (VPA) is indicated for treatment of febrile convulsions (FC) and very infrequently is associated with impairment of cognitive functions. We present a 8 years old girl treated with VPA for FC who manifest a dramatic behavioral and intellectual disorder confirmed by neuropsychological tests. Three weeks after a reduction of VPA dosis we observed a spectacular clinical improvement. Then, medication was discontinued with normalization of the neuropsychological items, till now, more than one year later. At all time plasmatics levels of VPA were in range and we never observed direct toxicity by the drug. This is an exceptional picture, and for our knowledge never has been reported during treatment of FC. We think that is important to inform of drug-induced abnormalities like this for avoid unnecessary exams to search for neurodegenerative disorders.
Considering the lack of studies on measures that increase the diagnostic distinction between Alzheimer's disease (AD) and mild cognitive impairment (MCI) and on the role of the Cambridge Cognitive Examination (CAMCOG) in this, our study aims to compare the utility of the CAMCOG, Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in helping to differentiate AD from MCI in elderly people with >4 years of schooling.
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