Kirsten I. Taylor

Improving the diagnostic accuracy of the Mini‐Mental State Examination

Introduction– We determined the diagnostic accuracy of the Mini‐Mental State Examination (MMSE) for dementia of the Alzheimer type (DAT) in an outpatient geriatric referral center in Switzerland. Material & methods– DAT patients and elderly controls were assigned to two groups: a validation sample (70 DAT patients; 50 controls) and a cross‐validation sample (133 DAT patients; 43 controls). A Receiver Operating Characteristic curve was generated to derive the optimal MMSE cut‐off score in the validation sample. Results ‐ The optimal MMSE cut‐off was < 26/30 (sensitivity of 74%, specificity of 100%). Adjustments for age and education were necessary. The cross‐validation confirmed these findings. Conclusion– In a clinical setting the MMSE cut‐off should be increased to < 26/30. A thorough neurobehavioral assessment is still necessary for a complete evaluation.

Hippocampal sclerosis dementia: a reappraisal

Hippocampal sclerosis (HpScl) is characterized by neuronal loss and gliosis in CA1 and subiculum of the hippocampus, and may be one contributing factor to dementia in old age. The term hippocampal sclerosis dementia (HpSclD) designates the presence of both hippocampal sclerotic lesions and a dementia syndrome. In the present review, we outline the pathological heterogeneity underlying HpSclD and discuss related disorders due to tau protein pathology and frontotemporal dementia with ubiquitin positive inclusions (FTLD-U). We also provide a detailed morphological description of ten of our own autopsied HpSclD cases, and compare these pathological findings with those reported in the literature. The lateralization of HpScl and the atrophy of the mammillary bodies were striking features in most of our cases. The main pathology consisted of tau positive lesions with a predominance of neuronal and glial pretangles in Ammon’s horn and the dentate gyrus. Neurofibrillary and ghost tangles in CA1 and the subiculum were scarce and thus insufficient to explain the hippocampal pyramidal cell loss. In some cases, tau pathology in the hippocampal formation coexisted with glial tau pathology in the frontal cortex. The most striking finding besides the tau pathology was the presence of concomitant neuronal cytoplasmic inclusions and neurites immunoreactive for the transactive response DNA-binding protein-43 (TDP-43) in the dentate gyrus and temporal neocortex, similar to those found in FTLD-U. Taken together, the pathology of HpSclD is indicative of a degenerative rather than a hypoxic/ischemic etiology of HpSclD. Presently, HpSclD may best be deemed a disorder with various neurodegenerative etiologies, most notably tauopathy and TDP-43 proteinopathy (i.e. FTLD-U). Each of these disease processes could either independently or concertedly account for the dementia syndrome in HpSclD.

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 objects 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.

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 recognition.

The evolution of meaning: Spatio-temporal dynamics of visual object recognition

Research on the spatio-temporal dynamics of visual object recognition suggests a recurrent, interactive model whereby an initial feedforward sweep through the ventral stream to prefrontal cortex is followed by recurrent interactions. However, critical questions remain regarding the factors that mediate the degree of recurrent interactions necessary for meaningful object recognition. The novel prediction we test here is that recurrent interactivity is driven by increasing semantic integration demands as defined by the complexity of semantic information required by the task and driven by the stimuli. To test this prediction, we recorded magnetoencephalography data while participants named living and nonliving objects during two naming tasks. We found that the spatio-temporal dynamics of neural activity were modulated by the level of semantic integration required. Specifically, source reconstructed time courses and phase synchronization measures showed increased recurrent interactions as a function of semantic integration demands. These findings demonstrate that the cortical dynamics of object processing are modulated by the complexity of semantic information required from the visual input.

Neural Basis of Semantic Memory: The conceptual structure account: A cognitive model of semantic memory and its neural instantiation

and Olga Mayenfisch Foundations is gratefully acknowledged (KIT). * Address for correspondence: Memory Clinic – Neuropsychology Center, University Hospital Basel, Schanzenstrasse 55, 4031 Basel, Switzerland, Tel.: ++ 41 (0)61 265 89 42, Fax: ++ 41 (0)61 265 37 88, e-mail: ktaylor@csl.psychol.cam.ac.uk. The Conceptual Structure Account: A cognitive model of semantic memory and its neural instantiation Kirsten I. Taylor, Helen E. Moss & Lorraine K. Tyler

Retrograde Amnesia in Dementia: Comparison of HIV-Associated Dementia, Alzheimer's Disease, and Huntington's Disease

Remote memory was assessed in persons with HIV-associated dementia (HIV-D), probable Alzheimers disease (AD), and Huntingtons disease (HD) and in healthy controls. The clinical groups were similar in overall dementia severity. Each clinical group exhibited impairments on remote memory tests relative to controls; however, temporally graded memory loss with selective preservation of older information was observed in the AD group but not the HD or HIV-D group. Analysis of cued retrieval indicated a preferential cuing benefit for the HIV-D and HD groups relative to the AD group. The similar pattern of remote memory performance demonstrated by the HIV-D and HD groups is a novel finding and suggests a subcortically mediated retrograde amnesia in HIV-D. The temporally graded pattern and the abnormal cued retrieval performance in the AD group are consistent with a consolidation deficit associated with extrahippocampal (cortical) and hippocampal damage.

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 damage.

Clinical course of neuropathologically confirmed frontal-variant Alzheimer's disease

Background A 66-year-old man presented with a 3-year history of personality changes marked by increasing apathy, social withdrawal and deficits in complex attention, and a 1-year history of progressive memory problems and difficulties in planning and carrying out complex tasks.Investigations Three neuropsychological examinations over 2 years, neurological examination, routine laboratory tests, brain MRI, single-photon emission CT scan, genetic analyses, and neuropathological examination.Diagnosis A clinical diagnosis of frontal-variant frontotemporal dementia was superseded by postmortem neuropathological evidence, which established a diagnosis of frontal-variant Alzheimers disease.Management The patient and his spouse were referred for counseling, and the patient was referred for follow-up examinations.

Category fluency is also predominantly affected in Swiss Alzheimer's disease patients

Objectives – To establish the comparative efficacy to differentiate between Swiss patients with dementia of the Alzheimer type (DAT) and elderly normal control subjects (NC) on two different verbal fluency tasks: category fluency and letter fluency. Material and methods – Fifty Swiss German DAT patients in the early stages of the disease and 50 matched normal control subjects were compared on letter and category fluency tasks. Results – DAT patients exhibited an overproportional impairment on category fluency as compared with letter fluency. Receiver operating characteristic curves (ROC) showed that category fluency correctly classified a significantly higher number of DAT patients and NC subjects (84%) than letter fluency (70%). Conclusion – As similar findings have been described for English‐speaking DAT patients, we conclude that deficiencies in category fluency are a general phenomenon, reflecting impaired structures of semantic knowledge occurring early in the course of Alzheimers disease.