Screening properties of the German IQCODE with a two-year time frame in MCI and early Alzheimer's disease

Background: The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is a widely used screening tool for dementia. We aimed to determine the ability of the German version of the 16-item IQCODE with a two-year time frame to discriminate healthy mature control participants (NC) from mild cognitive impairment (MCI) and probable early Alzheimer's disease (AD) patients (all with Mini-mental State Examination (MMSE) scores ≥ 24/30) and to optimize diagnostic discriminability by shortening the IQCODE. Methods: 453 NC (49.7% women, age = 69.5 years ± 8.2, education = 12.2 ± 2.9), 172 MCI patients (41.9% women, age = 71.5 years ± 8.8, education = 12.3 ± 3.1) and 208 AD patients (59.1% women, age = 76.0 years ± 6.4, education = 11.4 ± 2.9) participated. Stepwise binary logistic regression analyses (LR) were used to shorten the test. Receiver operating characteristic curves (ROC) determined sensitivities, specificities, and correct classification rates (CCRs) for (a) NC vs. all patients; (b) NC vs. MCI; and (c) NC vs. AD patients. Results: The mean IQCODE was 3.00 for NC, 3.35 for MCI, and 3.73 for AD. CCRs were 85.5% (NC-patient group), 79.9% (NC-MCI), and 90.7% (NC-AD), respectively. The diagnostic discriminability of the shortened 7-item IQCODE (i.e. items 1, 2, 3, 5, 7, 10, 14) was comparable with the longer version (i.e. 7-item CCRs: NC-patient group: 85.3%; NC-MCI: 80.1%, NC-AD: 90.5%). Conclusions: The German 16-item IQCODE with two-year time frame showed excellent screening properties for MCI and early AD patients. An abbreviated 7-item version demonstrated equally high diagnostic discriminability, thus allowing for more economical screenin

Early detection of Alzheimer's disease with a total score of the German CERAD

The goal of the present study was to evaluate the diagnostic discriminability of three different global scores for the German version of the Consortium to Establish a Registry on Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB). The CERAD-NAB was administered to 1100 healthy control participants [NC; Mini-Mental State Examination (MMSE) mean = 28.9] and 352 patients with very mild Alzheimer's disease (AD; MMSE mean = 26.1) at baseline and subsets of participants at follow-up an average of 2.4 (NC) and 1.2 (AD) years later. We calculated the following global scores: Chandler et al.'s (2005) score (summed raw scores), logistic regression on principal components analysis scores (PCA-LR), and logistic regression on demographically corrected CERAD-NAB variables (LR). Correct classification rates (CCR) were compared with areas under the receiver operating characteristics curves (AUC). The CCR of the LR score (AUC = .976) exceeded that of the PCA-LR, while the PCA-LR (AUC = .968) and Chandler (AUC = .968) scores performed comparably. Retest data improved the CCR of the PCA-LR and Chandler (trend) scores. Thus, for the German CERAD-NAB, Chandler et al.'s total score provided an effective global measure of cognitive functioning, whereby the inclusion of retest data tended to improve correct classification of individual cases. (JINS, 2010, 16, 910-920.

Simplified Vacuum Energy Expressions for Radial Backgrounds and Domain Walls

We extend our previous results of simplified expressions for functional determinants for radial Schr\"odinger operators to the computation of vacuum energy, or mass corrections, for static but spatially radial backgrounds, and for domain wall configurations. Our method is based on the zeta function approach to the Gel'fand-Yaglom theorem, suitably extended to higher dimensional systems on separable manifolds. We find new expressions that are easy to implement numerically, for both zero and nonzero temperature.Comment: 30 page

Progressive decline in gray and white matter integrity in de novo Parkinson's disease: An analysis of longitudinal Parkinson progression markers initiative diffusion tensor imaging data

Background: Progressive neuronal loss in neurodegenerative diseases such as Parkinson's disease (PD) is associated with progressive degeneration of associated white matter tracts as measured by diffusion tensor imaging (DTI). These findings may have diagnostic and functional implications but their value in de novo PD remains unknown. Here we analyzed longitudinal DTI data from Parkinson's Progression Markers Initiative de novo PD patients for changes over time relative to healthy control (HC) participants. Methods: Baseline and 1-year follow-up DTI MRI data from 71 PD patients and 45 HC PPMI participants were included in the analyses. Whole-brain fractional anisotropy (FA) and mean diffusivity (MD) images were compared for baseline group differences and group-by-time interactions. Baseline and 1-year changes in DTI values were correlated with changes in DTI measures and symptom severity, respectively. Results: At baseline, PD patients showed significantly increased FA in brainstem, cerebellar, anterior corpus callosal, inferior frontal and inferior fronto-occipital white matter and increased MD in primary sensorimotor and supplementary motor regions. Over 1 year PD patients showed a significantly stronger decline in FA compared to HC in the optic radiation and corpus callosum and parietal, occipital, posterior temporal, posterior thalamic, and vermis gray matter. Significant increases in MD were observed in white matter of the midbrain, optic radiation and corpus callosum, while gray matter of prefrontal, insular and posterior thalamic regions. Baseline brainstem FA white matter (WM) values predicted 1-year changes in FA white matter and MD gray matter values. White but not gray matter changes in both FA and MD were significantly associated with changes in symptom severity. Conclusion: Significant gray and white matter DTI alterations are observable at the time of PD diagnosis and expand in the first year of de novo PD to other cortical and white matter regions. This pattern of DTI changes is in line with preclinical and neuroanatomical studies suggesting that the increased spatial spread of alpha-synuclein neuropathology is the key mechanism of PD progression. Taken together, these findings suggest that DTI may serve as a sensitive biomarker of disease progression in early-stage PD

Medial perirhinal cortex disambiguates confusable objects

Our brain disambiguates the objects in our cluttered visual world seemingly effortlessly, enabling us to understand their significance and to act appropriately. The role of anteromedial temporal structures in this process, particularly the perirhinal cortex, is highly controversial. In some accounts, the perirhinal cortex is necessary for differentiating between perceptually and semantically confusable objects. Other models claim that the perirhinal cortex neither disambiguates perceptually confusable objects nor plays a unique role in semantic processing. One major hurdle to resolving this central debate is the fact that brain damage in human patients typically encompasses large portions of the anteromedial temporal lobe, such that the identification of individual substructures and precise neuroanatomical locus of the functional impairments has been difficult. We tested these competing accounts in patients with Alzheimer's disease with varying degrees of atrophy in anteromedial structures, including the perirhinal cortex. To assess the functional contribution of each anteromedial temporal region separately, we used a detailed region of interest approach. From each participant, we obtained magnetic resonance imaging scans and behavioural data from a picture naming task that contrasted naming performance with living and non-living things as a way of manipulating perceptual and semantic confusability; living things are more similar to one another than non-living things, which have more distinctive features. We manually traced neuroanatomical regions of interest on native-space cortical surface reconstructions to obtain mean thickness estimates for the lateral and medial perirhinal cortex and entorhinal cortex. Mean cortical thickness in each region of interest, and hippocampal volume, were submitted to regression analyses predicting naming performance. Importantly, atrophy of the medial perirhinal cortex, but not lateral perirhinal cortex, entorhinal cortex or hippocampus, significantly predicted naming performance on living relative to non-living things. These findings indicate that one specific anteromedial temporal lobe region—the medial perirhinal cortex—is necessary for the disambiguation of perceptually and semantically confusable objects. Taken together, these results support a hierarchical account of object processing, whereby the perirhinal cortex at the apex of the ventral object processing system is required to bind properties of not just perceptually, but also semantically confusable objects together, enabling their disambiguation from other similar objects and thus comprehension. Significantly, this model combining a hierarchical object processing architecture with a semantic feature statistic account explains why category-specific semantic impairments for living things are associated with anteromedial temporal lobe damage, and pinpoints the root of this syndrome to perirhinal cortex damag

From Perception to Conception: How Meaningful Objects Are Processed over Time

To recognize visual objects, our sensory perceptions are transformed through dynamic neural interactions into meaningful representations of the world but exactly how visual inputs invoke object meaning remains unclear. To address this issue, we apply a regression approach to magnetoencephalography data, modeling perceptual and conceptual variables. Key conceptual measures were derived from semantic feature-based models claiming shared features (e.g., has eyes) provide broad category information, while distinctive features (e.g., has a hump) are additionally required for more specific object identification. Our results show initial perceptual effects in visual cortex that are rapidly followed by semantic feature effects throughout ventral temporal cortex within the first 120 ms. Moreover, these early semantic effects reflect shared semantic feature information supporting coarse category-type distinctions. Post-200 ms, we observed the effects along the extent of ventral temporal cortex for both shared and distinctive features, which together allow for conceptual differentiation and object identification. By relating spatiotemporal neural activity to statistical feature-based measures of semantic knowledge, we demonstrate that qualitatively different kinds of perceptual and semantic information are extracted from visual objects over time, with rapid activation of shared object features followed by concomitant activation of distinctive features that together enable meaningful visual object recognitio

Functional determinants for radial operators

We derive simple new expressions, in various dimensions, for the functional determinant of a radially separable partial differential operator, thereby generalizing the one-dimensional result of Gel'fand and Yaglom to higher dimensions. We use the zeta function formalism, and the results agree with what one would obtain using the angular momentum cutoff method based on radial WKB. The final expression is numerically equal to an alternative expression derived in a Feynman diagrammatic approach, but is considerably simpler.Comment: 21 pages, uses axodraw.st

Feature Statistics Modulate the Activation of Meaning During Spoken Word Processing.

Understanding spoken words involves a rapid mapping from speech to conceptual representations. One distributed feature-based conceptual account assumes that the statistical characteristics of concepts' features--the number of concepts they occur in (distinctiveness/sharedness) and likelihood of co-occurrence (correlational strength)--determine conceptual activation. To test these claims, we investigated the role of distinctiveness/sharedness and correlational strength in speech-to-meaning mapping, using a lexical decision task and computational simulations. Responses were faster for concepts with higher sharedness, suggesting that shared features are facilitatory in tasks like lexical decision that require access to them. Correlational strength facilitated responses for slower participants, suggesting a time-sensitive co-occurrence-driven settling mechanism. The computational simulation showed similar effects, with early effects of shared features and later effects of correlational strength. These results support a general-to-specific account of conceptual processing, whereby early activation of shared features is followed by the gradual emergence of a specific target representation.This work was supported by a European Research Council Advanced Investigator grant (under the European Community's Seventh Framework Programme (FP7/2007-2013/ ERC Grant agreement no 249640) to LKT, and a Marie Curie Intra-European Fellowship and Swiss National Science Foundation Ambizione Fellowship to KIT. We thank Ken McRae and colleagues for making their property norm data available. We are very grateful to George Cree and Chris McNorgan for providing us with the MikeNet implementation of their model.This is the final published version. It first appeared at http://dx.doi.org/10.1111/cogs.1223

Comparison of Verbal Episodic Memory Measures: Consortium to Establish a Registry for Alzheimer's Disease—Neuropsychological Assessment Battery (CERAD-NAB) versus California Verbal Learning Test (CVLT)

Episodic memory is affected early in the course of dementia. Two well-established tests to assess verbal episodic memory functioning are the Word List task from the Consortium to Establish a Registry for Alzheimer's disease Neuropsychological Assessment Battery (CERAD-NAB) and the California Verbal Learning Test (CVLT). In clinical and/or research settings, patients are typically administered either one or the other test, making statistical comparisons difficult. This study aimed to (i) compare the z-scores of these two tests in patients with MCI and different types of dementia and (ii) establish formulae to transform CERAD-NAB scores into CVLT scores and vice versa. Sixty-five patients completed both tests for the first time and within 10 days of each other. Pearson correlation coefficients indicated that the two tests assess similar aspects of episodic memory and that the CVLT is more sensitive to subtle episodic memory impairments. Finally, conversion formulae are provided and their implementation illustrate

Objects and categories: feature statistics and object processing in the ventral stream.

Recognizing an object involves more than just visual analyses; its meaning must also be decoded. Extensive research has shown that processing the visual properties of objects relies on a hierarchically organized stream in ventral occipitotemporal cortex, with increasingly more complex visual features being coded from posterior to anterior sites culminating in the perirhinal cortex (PRC) in the anteromedial temporal lobe (aMTL). The neurobiological principles of the conceptual analysis of objects remain more controversial. Much research has focused on two neural regions-the fusiform gyrus and aMTL, both of which show semantic category differences, but of different types. fMRI studies show category differentiation in the fusiform gyrus, based on clusters of semantically similar objects, whereas category-specific deficits, specifically for living things, are associated with damage to the aMTL. These category-specific deficits for living things have been attributed to problems in differentiating between highly similar objects, a process that involves the PRC. To determine whether the PRC and the fusiform gyri contribute to different aspects of an object's meaning, with differentiation between confusable objects in the PRC and categorization based on object similarity in the fusiform, we carried out an fMRI study of object processing based on a feature-based model that characterizes the degree of semantic similarity and difference between objects and object categories. Participants saw 388 objects for which feature statistic information was available and named the objects at the basic level while undergoing fMRI scanning. After controlling for the effects of visual information, we found that feature statistics that capture similarity between objects formed category clusters in fusiform gyri, such that objects with many shared features (typical of living things) were associated with activity in the lateral fusiform gyri whereas objects with fewer shared features (typical of nonliving things) were associated with activity in the medial fusiform gyri. Significantly, a feature statistic reflecting differentiation between highly similar objects, enabling object-specific representations, was associated with bilateral PRC activity. These results confirm that the statistical characteristics of conceptual object features are coded in the ventral stream, supporting a conceptual feature-based hierarchy, and integrating disparate findings of category responses in fusiform gyri and category deficits in aMTL into a unifying neurocognitive framework.This work was supported by a grant from the Medical Research Council (G0500842) to L. K. T., a British Academy (Grant Number LRG-45583) grant to L. K. T. and K. I. T., a Newton Trust grant to L. K. T. and K. I. T., the European Research Council (ERC) under the European Community ʼs Seventh Framework Programme (FP7/2007 – 2013)/ERC (Grant Agreement Number 249640) to L. K. T., and a Swiss National Science Foundation Ambizione Fellowship (Grant Number PZ00P1_126493) to K. I. T.This is the accepted version of the original publication available at: http://dx.doi.org/10.1162/jocn_a_00419 in Journal of Cognitive Neuroscience http://www.mitpressjournals.org/loi/joc