DAT Patients Research Articles

Functional connectivity changes in two cortico-hippocampal networks of Alzheimer's disease continuum and their correlations with cognition: A SILCODE study.

The anterior-temporal (AT) and posterior-medial (PM) networks have been proposed to play pivotal roles in the memory processing associated with Alzheimer's disease (AD). Nevertheless, these two networks' intrinsic functional coupling characteristics are still vague in different AD stages. To explore the functional connectivity (FC) alterations within and across the AT&PM networks in patients with dementia of the Alzheimer's type (DAT), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and normal controls (NC). A total of 368 participants over 50 years old from the SILCODE study were recruited, including 99 NC, 134 SCD, 67 MCI, and 68 DAT patients. All the participants underwent a resting-state functional magnetic resonance imaging scan and a battery of neuropsychological tests. The 56 regions-of-interest of the AT&PM networks were defined broadly following existing literature. The FCs were calculated using DPABINet and compared among these four groups. Correlation analyses were performed on FCs and cognitive tests. Analysis of variance of all four groups showed significant alteration, mainly in the PM networks. Compared to NC, globally decreased FCs regarding AT&PM networks were observed in DAT and MCI patients, while globally increased FCs regarding AT&PM networks were observed in SCD. The decreased FCs in DAT were significantly correlated with the neuropsychological test on the memory domain. The FC alteration showed different patterns across the AD continuum, especially in individuals with SCD. The elevated FCs in the AT&PM networks of SCD may implicate certain compensating processes in the early stage of AD.

Deterioration and predictive values of semantic networks in mild cognitive impairment

Recent study has suggested semantic memory deterioration may be the earliest cognitive changes in Alzheimer's disease (AD). Few previous researchers have investigated specific changes in the semantic structures in the memory of patients with amnestic mild cognitive impairment (aMCI). This study examined the clustering performance in semantic fluency among 160 participants in various MCI subgroups (aMCI single domain, aMCI-sd, n = 30; aMCI multiple domain, aMCI-md, n = 30; non-aMCI multiple domain, naMCI-md, n = 10) as well as a group of mildly impaired individuals with dementia of AD type (DAT, n = 20), and a group of healthy controls (HC, n = 70). Compared with HC group, DAT patients presented deficient clustering in each semantic category related to living things. aMCI-sd group presented defective clustering when dealing with the clustering of items that may be more strongly associated with praxis and perceptual information in the categories that included inanimate living things. aMCI-md group displayed defective patterns similar to those in the aMCI-sd group; however, they displayed more profound deficits in clustering that may require perceptual information. Patients with naMCI-md preserved their ability to perform clustering on all of the categories. The poor clustering of items that may be more strongly associated with praxis could be used as a means of predicting conversion from aMCI-sd to DAT, whereas performance on items that may require perceptual information could be used to predict conversion among aMCI-md patients. These findings demonstrate the degree to which the semantic structures in memory can be used for the assessment of aMCI patients and prediction of conversion to DAT.

ABCA1-Labeled Exosomes in Serum Contain Higher MicroRNA-193b Levels in Alzheimer's Disease.

Objective We aimed to establish a method to determine whether microRNA-193b (miR-193b) levels in ABCA1-labeled serum exosomes might serve as a marker for the diagnosis of Alzheimer's disease. Methods We used immunocapture methods to determine the levels of ABCA1-labeled exosomal miR-193b in cultures of white blood cells (WBCs), red blood cells (RBCs), mouse hippocampal neuron HT-22 cells, and primary mouse neuronal cells. ABCA1-labeled exosomal miR-193b levels were also evaluated in the cerebrospinal fluid (CSF) and serum of APP/PS1 double-transgenic mice, as well as control subjects (n = 60) and study participants with subjective cognitive decline (SCD, n = 89), stage and mild cognitive impairment (MCI, n = 92), and dementia of the Alzheimer type (DAT, n = 92). Results ABCA1 levels of exosomes harvested from the medium of HT-22 cells and neurons were significantly higher than those of RBCs and WBCs (P < 0.05). Exosomal ABCA1 from the CSF of APP/PS1 mice were transmitted to the serum of wild-type mice after injection, and high miR-193b levels were observed in both the serum and CSF after injection. The ABCA1-labeled exosomal miR-193b levels were higher in the CSF of MCI and DAT patients compared with the CSF of the control group (P < 0.05). The ABCA1-labeled exosomal miR-193b were also slightly higher (P > 0.05) in the serum of SCD patients and significantly higher in the serum of MCI and DAT patients compared with the serum of the control group (P < 0.05). Conclusion This study provides a method to capture specific exosomes. Detection of serum exosomes labeled with ABCA1 may facilitate the early diagnosis of AD.

MicroRNA-135a in ABCA1-labeled Exosome is a Serum Biomarker Candidate for Alzheimer's Disease

ObjectiveIn the present study, the ABCA1 was used as a label to capture specific exosomes, the level of ABCA1-labeled exosomal microRNA-135a (miR-135a) was evaluated for the diagnosis of Alzheimer's disease (AD), especially in patients with early stages of AD. MethodsThis is a preliminary research focused on the levels of ABCA1 in WBCs, RBCs, HT-22 cells, and neuron cells. The diagnostic value of ABCA1-labeled exosomal miR-135a was examined using the CSF and serum of APP/PS1 double transgenic mice, and 152 patients with SCD, 131 patients with MCI, 198 patients with DAT, and 30 control subjects. ResultsThe level of ABCA1 exosomes harvested from HT-22 cells and neuron culture medium was significantly higher compared to that of RBCs and WBCs (P < 0.05). The levels of ABCA1-labeled exosomal miR-135a increased in the CSF of MCI and DAT group compared to those of control group (P < 0.05), slightly increased (P > 0.05) in the serum of SCD patient group, and significantly increased in MCI and DAT patient groups compared to those of the control group (P < 0.05). ConclusionThis study outlines a method to capture specific exosomes and detect them using immunological methods, which is more efficient for early diagnosis of AD.

Sentence comprehension in patients with dementia of the Alzheimer's type.

Sentence comprehension is diminished in patients with dementia of the Alzheimer’s type (DAT). However, the underlying reason for such deficits is still not entirely clear. The Syntactic Deficit Hypothesis attributes sentence comprehension deficits in DAT patients to the impairment in syntactic ability, whereas the Processing Resource Deficit Hypothesis proposes that sentence comprehension deficits are the result of working memory deficiency. This study investigated the deficits in sentence comprehension in Chinese-speaking DAT patients with different degrees of severity using sentence-picture matching tasks. The study revealed a significant effect of syntactic complexity in patients and healthy controls, but the effect was stronger in patients than in healthy controls. When working memory demand was minimized, the effect of syntactic complexity was only significant in patients with moderate DAT, but not in healthy controls or those with mild DAT. The findings suggest that in patients with mild DAT, working memory decline was the major source of sentence comprehension difficulty and in patients with moderate DAT, working memory decline and syntactic impairment jointly contributed to the impairments in sentence comprehension. The source of sentence comprehension deficits varied with degree of dementia severity.

Spontaneous spatial information provided by dementia patients and elderly controls in narratives

Patients diagnosed with dementia of the Alzheimer’s type (DAT) often show two symptoms early on: the inability to navigate space effectively and a deterioration of their language skills, especially on semantic tasks. In this work, I look at whether the inability to navigate space is reflected in the spontaneous speech of DAT patients. Through a corpus analysis of narratives by DAT and control participants, I investigate the hypothesis that DAT patients provide less spatial information than healthy controls (mirroring the decline of effective spatial reasoning in language production). This hypothesis was not supported for locative/stative descriptions using in, on, and at; both groups included this information equally often. However, significant differences between the groups were found for the inclusion of the spatial terms left and right as well directional/dynamic spatial information indicated by into, onto, from, and to. This difference between locative/stative and directional/dynamic spatial information has not previously been reported. I argue that it aligns with Chatterjee’s (2008) proposal of the relational features of spatial language and that these features can be differently affected in DAT patients, aligning it with the spatial navigation impairment in these participants.

Validation of the Korean-Everyday Cognition (K-ECog).

BackgroundIn the early diagnosis of dementia, an important factor is the evaluation of activities of daily living. The Everyday Cognition (ECog) scale was developed to measure functional changes that are the everyday correlates of specific neuropsychological impairments. This study aimed to examine the validity of the Korean version of Everyday Cognition (K-ECog).MethodsThe participants were 268 cognitively normal older adults (NA), 151 amnestic mild cognitive impairment (aMCI), and 77 dementia of the Alzheimer's type (DAT). The Korean-Mini Mental State Examination (K-MMSE), Korean-Montreal Cognitive Assessment (K-MoCA), and Short form of the Geriatric Depression Scale (SGDS) were administered to all the participants. The K-ECog and Korean-Instrumental Activities of Daily Living (K-IADL) were rated by their informants.ResultsInternal consistency (Cronbach's α) of K-ECog global function was 0.93, and its test-retest reliability (Pearson's r) was 0.73. K-ECog was significantly correlated with K-IADL (0.66), K-MMSE (−0.38), and K-MoCA (−0.26). Confirmatory factor analysis of K-ECog yielded seven factor model that the original ECog proposed. K-ECog global score and six domain scores were significantly different across the NA, aMCI, and DAT groups. Receiver operating characteristic curve analyses showed that K-ECog effectively differentiated aMCI and DAT patients from NA, suggesting that K-ECog is as sensitive for detecting functional impairments as K-IADL. The proposed optimal cut-off score to differentiate aMCI from NA was 1.41.ConclusionK-ECog is proven reliable and valid for clinical use. K-ECog can be used to distinguish very early stages of impaired ADL and cognitive impairment in the community.

Evaluation of Cerebrospinal Fluid Neurofilament Light Chain as a Routine Biomarker in a Memory Clinic.

Systematic evaluation of biomarkers in representative populations is needed to validate their clinical utility. In this work, we assessed the diagnostic performance of cerebrospinal fluid (CSF) neurofilament light chain (NfL) in a neurocognitive clinical setting. A total of 51 patients with different cognitive clinical syndromes and 11 cognitively normal individuals were evaluated in a memory clinic in Argentina. Clinical conditions included mild cognitive impairment (MCI, n = 12), dementia of Alzheimer's type (DAT, n = 14), behavioral variant frontotemporal dementia (bvFTD, n = 13), and primary progressive aphasia (logopenic [n = 6], semantic [n = 2], and nonfluent [n = 4]). We quantified CSF NfL and core Alzheimer's disease biomarkers using commercially available ELISA kits. Cortical thickness was analyzed on brain magnetic resonance imaging scans from 10 controls and 10 patients. CSF NfL was significantly increased in MCI, FTD, and DAT patients compared with controls (Kruskal-Wallis, p < .0001). Interestingly, receiver operating characteristic curve analysis showed the highest area under the curve (AUC) value when analyzing control versus bvFTD patients (AUC = 0.9441). Also, we observed a marginally significant correlation between NfL levels and left orbitofrontal cortex thickness in a small group of patients with FTD. Overall, our results further support CSF NfL as a promising biomarker in the diagnostic workup of bvFTD.

Episodic memory for natural and transformed food

It has been proposed that the conceptual knowledge of food and its putative subdivision into natural (i.e., fruit/vegetables) and transformed (i.e., food that underwent thermic or non-thermic processing) may follow the living/non-living distinction. In the present study, we investigated whether the advantage for living things compared to non-living things observed in episodic memory (the so-called animacy effect) extends to natural foods and transformed foods respectively. We pursued this issue in two experiments. In Experiment 1, we measured episodic memory for natural and transformed foods in young participants. In Experiment 2, we enrolled dementia-free centenarians, patients with Alzheimer's disease (DAT), Progressive primary aphasia (PPA), and healthy controls whose episodic memory was also tested for living/non-living things. Results showed that young participants had better recognition memory for transformed foods compared to natural foods. This difference disappeared in centenarians and patients. However, centenarians and PPA exhibited enhanced levels of false alarms (FA) with natural food, and DAT patients with both natural and transformed food. As far as the living/non-living distinction is concerned, the episodic memory for the living category appears more resilient to the decline compared to the non-living category in patients, particularly those with PPA. In conclusion, our study shows that transformed food is better remembered than natural food, suggesting that it is more salient and possibly relevant from an evolutionary perspective. The natural/transformed distinction appears susceptible to erosion only in the presence of a high degree of episodic memory impairment. These results offer novel insight on episodic memory of food, and also extend the current knowledge on the animacy effect in episodic memory.

Diagnostic and Prescription Behavior of General Practitioners and Specialist Physicians in Patients with Dementia in 2005 and 2015 in Germany

Did the diagnostic and treatment behavior of general practitioners and specialists in patients with dementia (PWD) change in Germany over a period of 11 years (2005 vs. 2015)? We performed a retrospective, database-based evaluation of diagnostic and prescription data from more than 398 general practices (GP) and 50 specialist practices (SP). Compared to 2005, in 2015, the number of PWD had increased by 40.7 % in GP and by 52.4 % in SP. The proportion of patients with DAT (Alzheimer's Disease) had increased from 45.8 % to 61.7 % in SP. The latter changes are different from those in GP, where the proportion of patients with DAT had decreased from 20.8 % to 19.2 %. On average, each individual GP treated 29.9 PWD in 2015 (2005: 21.3), of which 5.9 were DAT patients (2005:4.4), and 1.7 DAT patients received an antidementia drug (2005: 1.3). On the other hand, an average of 115.4 PWD were diagnosed in SP in 2015 (2005: 75.7), 71.2 of which were DAT patients (2005: 34.7). 54.4 received an antidementia drug (2005: 23.9). Improvements in the diagnosis of dementia and the prescription of antidementia drugs were only found in SP. In light of their comparatively low potential for change, whether GP will change their diagnostic and treatment behavior in the future and how SP can be better integrated into the process of outpatient dementia care remains to be seen.

HIGH DOSE DONEPEZIL WITH SOLIFENACIN (CPC-201) IMPROVES SAFETY AND INITIAL EFFICACY IN ALZHEIMER’S DISEASE

Cholinesterase inhibitors (ChEIs) remain the therapeutic mainstay for dementia of the Alzheimer’s type (DAT) despite dose-limiting adverse events (AEs) and modest efficacy. Nevertheless, PET studies indicate that ChEIs, at maximum tolerable dose (MTD), inhibit the target CNS enzyme by only about 30%, while non-clinical and clinical results suggest higher ChEI doses confer greater cognitive benefit. Moreover, Phase I studies supported hypothesis that co-administration of a peripheral anticholinergic reduces dose-limiting AEs, enabling the safe/tolerable use of higher ChEI doses and thus potentially improving antidementia efficacy. A phase IIa single-blind, crossover trial was conducted to further evaluate this hypothesis in 41 moderate (MMSE 10-20) DAT patients being successfully treated with 10 mg/day donepezil. The anticholinergic solifenacin was first titrated to 15 mg/day and then donepezil escalated to each patient’s MTD or protocol limit (40 mg/day). Patients continued at their MTD for 3 additional months. At the end of dose titration (week 14), the median MTD of donepezil (primary endpoint), given orally with solifenacin as CPC-201, increased to 40 mg/day (p <.0001; n = 33 in ITT population); 88% of patients reached this maximum allowable dose, which did not change significantly during following 3 months. Cognitive function, measured by the ADAS-cog scale at end of dose titration and during dose maintenance (weeks 18, 22 and 26 in n = 23 per protocol population) was consistently improved compared with baseline; adjustment for natural disease progression and the previously realized response to 10 mg donepezil (approximated from published RCT results) yielded a mean (± SEM) benefit of 5.4 ± .84 points (p < .05) compared to historic placebo (trial not powered for secondary efficacy measures). Combined Clinical Global Impression (CGI-I) scores from investigators and caregivers at 26 weeks averaged 3.1 ± .20 points, thus improving by .94 ± .20 points (p < .001; n = 16). At MTD, the frequency of gastrointestinal AEs declined by over 80% of that reported in trials of 10 and 23 mg donepezil. No drug-related drop-outs or SAEs, and no new AEs or evidence of solifenacin toxicity occurred. Attenuating donepezil AEs with soifenacin enables the safe/tolerable administration of higher ChEI doses that could improve antidementia efficacy.

MicroRNA-135a and -200b, potential Biomarkers for Alzheimer׳s disease, regulate β secretase and amyloid precursor protein

Amyloid precursor protein (APP) and β-site amyloid precursor protein cleaving enzyme (BACE-1) play important roles in the generation of Alzheimer׳s disease (AD), a progressive neurodegenerative disorder. In the present study, microRNA (miR) microarray was used to analyze the miR expression profiles in the hippocampi from APP/PS1 transgenic and wild type mice. The miRs with significant alteration and putative targets on APP or BACE-1 were retrieved (miR-135a, -200b and -429). The deregulations of these miRs were confirmed in mice and further verified in AD patient samples by qPCR. Primary mouse hippocampal neurons, SH-SY5Y and HEK293 cells were used to study the function of miRs on APP and BACE-1. We found that miR-135a, which was downregulated significantly in hippocampi from APP/PS1 transgenic mice compared with the wild type control, directly interacted with the 3′–UTR of BACE-1 and repressed its expression and activity. On the other hand, miR-200b and -429, which were downregulated significantly in hippocampi from APP/PS1 transgenic mice compared with the wild type control, targeted the 3′–UTR of APP and repressed its expression. Furthermore, Aβ42 could downregulate miR-200b expression which may generate a vicious cycle resulted in accumulating Aβ42. The levels of miR-135a and -200b in the serum of DAT group were significantly lower than that of control groups (P<0.05). The serum miR-200b level of MCI group was higher than that of DAT group (P<0.05) and lower than that of control group (P<0.05). We also found decreased miR-135a and -200b levels in the cerebrospinal fluid of DAT group compared with the control group (P<0.05). In conclusion, these findings showed that miR-135a, -200b and -429 may take part in the progress of AD; miR-200b was of great potential as noninvasive and easily detected blood-based biomarkers of MCI and DAT patients.

Posterior AD-type pathology: cognitive subtypes emerging from a cluster analysis.

Background. “Posterior shift” of the neuropathological changes of Alzheimer's disease (AD) produces a syndrome (posterior cortical atrophy) (PCA) dominated by high-level visual deficits. Objective. To explore in patients with AD-type pathology whether a data-driven analysis (cluster analysis) based on neuropsychological findings resulted in the emergence of different subgroups of patients; in particular to find out whether it was possible to identify patients with visuospatial deficits consistent with the hypothesis that PCA is a “dorsal stream” syndrome or, rather, whether there were subgroups of patients with different types of impairment within the high-level visual domain. Methods. 23 PCA and 16 DAT patients were studied. By a principal component analysis performed on a wide range of neuropsychological tasks, 15 variables were obtained that loaded onto five main factors (memory, language, perceptual, visuospatial, and calculation) which entered a hierarchical cluster analysis. Results. Four clusters of cognitive impairment emerged: visuospatial/perceptual, memory, perceptual/calculation, and language. Only in the first cluster a visuospatial deficit clearly emerged. Conclusions. AD pathology produces not only variants dominated by memory (DAT) and, to a lesser extent, visuospatial deficit (PCA), but also other distinct syndromic subtypes with disorders in visual perception and language which reflect a different vulnerability of specific functional networks.

Demensdiagnostikk - automatisert kvantifisering av hjernestrukturer

The aim of the present study was to examine the usefulness of a fully automatic quantification of brain structures by means of magnetic resonance imaging (MRI) for diagnosing dementia of the Alzheimer's type (DAT). MRI scans of the brains of 122 patients, referred to a memory clinic, were analysed using Neuroquant® software, which quantifies the volume of various brain structures. Clinical diagnoses were made by two doctors without knowledge of the MRI results. We performed Receiver Operating Characteristic analyses and calculated the area under the curve (AUC). A value of 1 means that all ill patients have been diagnosed as diseased and no patient has been falsely diagnosed as diseased. The mean age of the patients was 67.2 years (SD 10.5 years), 60 % were men, 63 had DAT, 24 had another type of dementia, 25 had mild cognitive impairment (MCI) and ten had subjective cognitive impairment (SCI). In the comparison between DAT patients and patients with SCI or MCI, seven of eleven volumes were significantly larger than AUC 0.5. Positive and negative likelihood ratios were less than 5 and more than 0.2, respectively, for the best limit values of the volumes. Apart from the cerebellum (AUC 0.67), none of the brain structures was significantly different from AUC 0.5 in patients with dementia conditions other than dementia Alzheimer's type. MRI scans with Neuroquant analyses cannot be used alone to distinguish between persons with dementia of Alzheimer's type and persons without dementia.

Effects of education, literacy, and dementia on the Clock Drawing Test performance

The Clock Drawing Test (CDT) has been recognized as an effective tool for dementia detection. This study investigated the clock drawing performance of 240 non-demented elderly Korean people with a wide-range of educational levels and 28 patients with mild dementia of the Alzheimer's type (DAT). We examined the effects of demographic factors, including education, and established norms for the elderly population. We found that the educational attainment and literacy status of older people influenced performance on the CDT significantly (p < .001). Furthermore, qualitative error analysis revealed that normal participants with low educational background committed errors similar to errors of the DAT patients. The DAT patients performed significantly worse than the non-demented participants in the CDT Total score (p < .001). However, the CDT has better criterion validity in participants with more than 6 years of education. In conclusion, the CDT performance in older people who are either illiterate or with 6 or less years of education should be interpreted with caution. Conceptual errors in the CDT can be the result of not only dementia but also lack of education.

Relationship between EEG alteration and cognitive function in the patients with MCI and DAT

Objective To investigate relations between EEG changes and cognitive function, and early di-agnostically significance of EEG measures in Alzheimer s disease. Methods One hundred and forty controls, 78 patients with mild cognitive impairment ( MCI) and 45 dementia with Alzheimer' s type ( DAT) underwent neuropsychological and EEG investigations. The relative power was separately computed for delta, theta, alpha1, alpha2 beta 1, and beta 2 frequency bands. Results Comparing with normal controls, the MCI and DAT patients had higher( 19.2% and 37.6% ) EEG alterations ( poor regulation, increased slow-wave and decreased rapid-wave); delta (5.00 ±2.79) and theta (1.93 ±1.02) relative powers were increased in MCI patients on prefrontal and temporal and in DAT patients (5.52 ±2.54 and 2.76 ±2.13) on all sites as compared with controls (3.98 ± 1.47 and 1.61 ±0.75). In DAT, increased delta and theta powers were related to decreased performance on tests of memory ( -0.388 and -0.352) and cognition ( -0.339 and -0.359). The correct rate of EEG distinguishing between MCI and controls was equal to 63.4% , and between DAT and controls was equal to 73. 5%. Conclusion The EEG power measures might prove useful in predicting cognitive decline and in early diagnosis of AD dementia. Key words: Alzheimer's disease; Mild cognitive impairment; Cognitive function; EEG

FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer’s disease

We report the first clinicopathological series of longitudinal FDG-PET scans in post-mortem (PM) verified cognitively normal elderly (NL) followed to the onset of Alzheimer's-type dementia (DAT), and in patients with mild DAT with progressive cognitive deterioration. Four NL subjects and three patients with mild DAT received longitudinal clinical, neuropsychological and dynamic FDG-PET examinations with arterial input functions. NL subjects were followed for 13 +/- 5 years, received FDG-PET examinations over 7 +/- 2 years, and autopsy 6 +/- 3 years after the last FDG-PET. Two NL declined to mild cognitive impairment (MCI), and two developed probable DAT before death. DAT patients were followed for 9 +/- 3 years, received FDG-PET examinations over 3 +/- 2 years, and autopsy 7 +/- 1 years after the last FDG-PET. Two DAT patients progressed to moderate-to-severe dementia and one developed vascular dementia. The two NL subjects who declined to DAT received a PM diagnosis of definite AD. Their FDG-PET scans indicated a progression of deficits in the cerebral metabolic rate for glucose (CMRglc) from the hippocampus to the parietotemporal and posterior cingulate cortices. One DAT patient showed AD with diffuse Lewy body disease (LBD) at PM, and her last in vivo PET was indicative of possible LBD for the presence of occipital as well as parietotemporal hypometabolism. Progressive CMRglc reductions on FDG-PET occur years in advance of clinical DAT symptoms in patients with pathologically verified disease. The FDG-PET profiles in life were consistent with the PM diagnosis.

The role of cognition in context-dependent language use: Evidence from Alzheimer's disease

Deixis is a linguistic form that can functionally replace nouns in communication, and it is the most obvious tool to investigate how language is used in relation to communicative context. In this paper, we expand upon our previous study on language use in dementia of the Alzheimer type – DAT [March, E. G., Wales, R., & Pattison, P. (2006). The uses of nouns and deixis in discourse production in Alzheimer's disease. Journal of Neurolinguistics, 19, 311–340], and investigate the role of cognition in deictic use (spatial and person) and noun use across four distinct discourse task conditions. The participants are 26 DAT patients and 26 demographically matched healthy elderly, over the age of 65 years old and of lower education backgrounds. Neuropsychological measures include tests of language, working memory and level of general cognitive functioning. Correlation and regression analyses reveal that the role of cognition is more prominent in the use of spatial deixis than it is in the uses of nouns and person deixis, while the role of working memory is evident even at the noun use level. The findings vary across the four discourse tasks, providing empirical evidence on the role of communicative context in the interplay between language use and cognition.

Semantic Clustering Indexes for the Hopkins Verbal Learning Test�Revised: Initial Exploration in Elder Control and Dementia Groups

This study examined the validity of semantic clustering indexes developed for the Hopkins Verbal Learning Test�Revised (HVLT�R). Participants were healthy adults and patients diagnosed with probable dementia of the Alzheimer's type (DAT) or vascular dementia (VaD). Neuropsychological test records, which included the HVLT�R, were collected from an archival database. Ratio semantic clustering (RSC) scores were calculated for each HVLT�R recall trial. Factor analysis including RSC and other HVLT�R scores yielded high loadings of RSC scores on a distinct clustering factor. Group comparisons showed that normal controls had higher HVLT�R recall and RSC scores than DAT and VaD patients. Only the DAT group showed significant decline in RSC from the final learning trial to delayed recall, and only the DAT group performed more poorly than controls on other semantic processing measures (e.g., HVLT�R semantically-related false positives, Boston Naming Test). Results suggest that these newly developed semantic clustering indexes are easily calculated and potentially useful for discriminating between elder controls and dementia patients.

Semantic relevance, domain specificity and the sensory/functional theory of category-specificity

According to the sensory/functional theory of semantic memory, Living items rely more on Sensory knowledge than Non-living ones. The sensory/functional explanation of category-specificity assumes that semantic features are organised on the basis of their content. We report here a study on DAT patients with impaired performance on Living items and tests of Sensory knowledge, and show that this impairment not only disappears after parcelling out semantic relevance, but is also reversed if this parameter is appropriately manipulated. Although semantic relevance model predicts these results [Sartori, G., & Lombardi, L. (2004). Semantic relevance and semantic disorders. Journal of Cognitive Neuroscience, 16, 439–452], they run counter to both the sensory/functional theory and the domain-specific theory of category-specific impairment.