Impairment In Early Stages Research Articles

Early Posterior Negativity as Facial Emotion Recognition Index in Children With Attention Deficit Hyperactivity Disorder

Introduction:Studies indicate that children with Attention Deficit Hyperactivity Disorder (ADHD) have deficits in social and emotional functions. It can be hypothesized that these children have some deficits in early stages of facial emotion discrimination. Based on this hypothesis, the present study investigated neural correlates of early visual processing during emotional face recognition in this group compared with typically developing children using the Event-Related Potentials (ERPs).Methods:Nineteen boys between the ages of 7 and 11 years diagnosed with ADHD (Combined type) based on DSM-IV-TR classification were compared with 19 typically developing children matched on age and gender. The participants performed an emotional face recognition task while their brain activities were recorded using the event-related potentials procedure.Results:A significant reduction in the Early Posterior Negativity (EPN) for happy and angry faces has been revealed in ADHD children compared to normal ones (P<0.05).Conclusion:The present study supports the notion that individuals with ADHD have some impairments in early stage of emotion processing which can leading to their misinterpretation of emotion in faces.

The Arcuate Fasciculus Network and Verbal Deficits in Psychosis.

BackgroundVerbal learning (VL) and fluency (VF) are prominent cognitive deficits in psychosis, of which the precise neuroanatomical contributions are not fully understood. We investigated the arcuate fasciculus (AF) and its associated cortical regions to identify structural abnormalities contributing to these verbal impairments in early stages of psychotic illness.MethodsTwenty-six individuals with recent-onset psychosis and 27 healthy controls underwent cognitive testing (MATRICS Consensus Cognitive Battery) and structural/diffusion-weighted MRI. Bilaterally, AF anisotropy and cortical thickness, surface area and volume of seven cortical regions were investigated in relation to VL and VF performance in both groups.ResultsReduced right superior temporal gyrus surface area and volume related to better VF in controls. In psychosis, greater right pars opercularis volume and reduced left lateralization of this region related to better VL, while greater right long AF fractional anisotropy and right pars orbitalis volume related to better VF, these findings not present in controls. Psychosis had reduced right pars orbitalis thickness compared to controls.ConclusionAnatomical substrates for normal processing of VL and VF appear altered in recent-onset psychosis. A possible aberrant role of the right hemisphere arcuate fasciculus and fronto-temporal cortical regions in psychosis may contribute to deficits in VL and VF.

The value of symmetrical ambulatory arterial stiffness index should be noted in prediction of early renal impairment in patients with essential hypertension

Objective To investigate the predictive value of symmetrical ambulatory arterial stiffness index (S-AASI) in detecting early renal impairment of patients with essential hypertension. Methods Totally 245 consecutive out-patients were confirmed with essential hypertension, and were divided into group A (56 cases), group B (64 cases), group C (72 cases), and group D (53 cases) according to the quartile of S-AASI. The combination testing of serum cystatin C, serum β2-microglobulin as well as urine microalbumin to creatinine ratio were implemented as laboratory diagnosis index of renal impairment in early stage and 109 essential hypertension patients were diagnosed with early renal impairment. The parameters were compared among 4 groups. Pearson correlation analysis and partial correlation analysis were performed to confirm the relationship between the markers of early renal impairment and S-AASI. The predictive value of S-AASI to detect early renal injury was evaluated by analyzing Receiver Operating Characteristic (ROC) curve. Results With the rising of S-AASI, age as well as 24 hours mean systolic blood pressure (24 h SBP), serum cystatin C, serum β2-microglobulin, urine microalbumin to creatinine ratio and the incidence rate of early renal injury went notably higher while estimated glomerular filtration rate (eGFR) decreased significantly. After controlling for age, correlation test showed S-AASI was positively correlated with24hSBP, serum cystatin C, serumβ2-microglobulin, urine microalbumin to creatinine ratio(r=0.392, 0.627, 0.514 and 0.643 respectively, P<0.05)and negatively correlated with eGFR(r=-0.312, P<0.05). The 24 hours mean diastolic blood pressure (24 h DBP) was uncorrelated with S-AASI. Area under ROC curve of S-AASI for diagnosis of hypertensive renal impairment was 0.885. The critical value of S-AASI was 0.17, the sensitivity, specificity, positive predictive value, and negative predictive value were 92.7%, 65.2%, 68.5%, and 91.7%, respectively. Conclusions When S-AASI was detected above 0.17, patients with hypertension had a higher risk of renal impairment. Higher S-AASI was correlated with worse early renal impairment laboratory indexes. The predictive accuracy of S-AASI for early hypertensive renal impairment was medium. Key words: Arteriosclerosis; Hypertension/CO; Kidney diseases/CO; Forecasting

Emotional Face Recognition in Children With Attention Deficit/Hyperactivity Disorder: Evidence From Event Related Gamma Oscillation.

Introduction:Children with attention-deficit/hyperactivity disorder (ADHD) have some impairment in emotional relationship which can be due to problems in emotional processing. The present study investigated neural correlates of early stages of emotional face processing in this group compared with typically developing children using the Gamma Band Activity (GBA).Methods:A total of 19 children diagnosed with ADHD (Combined type) based on DSM-IV classification were compared with 19 typically developing children matched on age, gender, and IQ. The participants performed an emotional face recognition while their brain activities were recorded using an event-related oscillation procedure.Results:The results indicated that ADHD children compared to normal group showed a significant reduction in the gamma band activity, which is thought to reflect early perceptual emotion discrimination for happy and angry emotions (P<0.05).Conclusion:The present study supports the notion that individuals with ADHD have some impairments in early stage of emotion processing which can cause their misinterpretation of emotional faces.

Inter-hemispheric functional dysconnectivity mediates the association of corpus callosum degeneration with memory impairment in AD and amnestic MCI.

Evidences suggested that both corpus callosum (CC) degeneration and alternations of homotopic inter-hemispheric functional connectivity (FC) are present in Alzheimer’s disease (AD). However, the associations between region-specific CC degeneration and homotopic inter-hemispheric FC and their relationships with memory deficits in AD remain uncharacterized. We hypothesized that selective CC degeneration is associated with memory impairment in AD and amnestic mild cognitive impairment (aMCI), which is mediated by homotopic inter-hemispheric functional dysconnectivity. Using structural magnetic resonance imaging (MRI) and task-free functional MRI, we assessed the CC volume and inter-hemispheric FC in 66 healthy controls, 41 aMCI and 41 AD. As expected, AD had CC degeneration and attenuated inter-hemispheric homotopic FC. Nevertheless, aMCI had relatively less severe CC degeneration (mainly in mid-anterior, central, and mid-posterior) and no reduction in inter-hemispheric homotopic FC. The degeneration of each CC sub-region was associated with specific inter-hemispheric homotopic functional disconnections in AD and aMCI. More importantly, impairment of inter-hemispheric homotopic FC partially mediated the association between CC (particularly the central and posterior parts) degeneration and memory deficit. Notably, these results remained after controlling for hippocampal volume. Our findings shed light on how CC degeneration and the related inter-hemispheric FC impact memory impairment in early stage of AD.

A hypothetical model to solve the controversy over the involvement of UCP2 in palmitate-induced β-cell dysfunction

The aim of this article is to solve an existing controversy over the involvement of uncoupling protein-2 in the impairment of glucose-stimulated insulin secretion induced by chronic exposure of β-cells to palmitate. We analyzed and compared the results of studies that support and that deny the involvement of uncoupling protein-2 in this impairment. We observed that this impairment could occur in multiple stages. We provide a model in which palmitate-induced impairment of glucose-stimulated insulin secretion is proposed to occur in two stages, early stage and late stage, depending on the integrity of electron supply (glycolysis and Krebs cycle) and transport system through electron transport chain after palmitate treatment. Prolonged exposure of β-cells to palmitate can impair this system. Early-stage impairment occurs due to uncoupling by uncoupling protein-2 when this system is still intact. When this system becomes impaired, late-stage impairment occurs mainly due to reduced glucose-stimulated adenosine triphosphate production independent of uncoupling by uncoupling protein-2. The change in glucose-stimulated oxygen uptake after palmitate treatment reflects the integrity of this system and can be used to differentiate between the two stages. Some β-cells lines and islets appear to be more resistant to palmitate-induced impairment of electron supply and transport system than others, and therefore early stage is prominent in the more resistant cell lines and less prominent or absent in the less resistant cell lines. This may help to resolve the pathogenesis of diabetes and to monitor the progression of palmitate-induced β-cell dysfunction.

Your misery is no longer my pleasure: Reduced schadenfreude in Huntington's disease families

Schadenfreude – pleasure at others' misfortunes – has been systematically related to ventral striatum activity. This brain region is affected early in individuals with manifest and pre-manifest Huntington's disease (HD). However, the experience of schadenfreude has not yet been investigated in HD. In this study, 21 manifest HD patients, 19 first-degree asymptomatic relatives, and 23 healthy controls performed an experimental task designed to trigger schadenfreude, envy (another social emotion acting as an affective control condition), and control situations. Both HD patients and first-degree relatives experienced lower schadenfreude in response to others' misfortunes, with no group differences in ratings of envy and control conditions. These results offer unprecedented evidence of a highly specific impairment in reward processing, extending previous reports in manifest and pre-manifest HD individuals. Moreover, these findings suggest that early striatal impairments may be related to reduced feelings of schadenfreude. In sum, our work contributes to the understanding of emotional impairments in early stages of HD, while shedding light on their neural correlates.

Abstract WP425: Blood Brain Barrier Disruption and Vascular Cognitive Impairment in Early Stages of Heart Failure Development in Tgαq*44 Mice

Introduction: Advanced heart failure (HF) with subsequent hypoperfusion is a well-recognized clinical risk factor for the development of Vascular Cognitive Impairment (VCI), with early mechanisms yet to be identified. Tgαq*44 mice are a transgenic model of slowly developing HF and peripheral endothelial dysfunction due to cardiomyocyte-specific overexpression of G protein αq*44 where VCI has not been assessed. Hypothesis: We hypothesized that Tgαq*44 mice develop VCI at early/compensated stages of HF, due to dysfunction of brain endothelium - essential for the blood brain barrier (BBB) function. Methods: Tgαq*44 and control FVB mice at the age of 6, 10 and 14 months (m) were studied. Novel Object Recognition (NOR) test (n=8/gr.; 6,10,14 m) was used to assess cognition. BBB permeability was assessed (n=3/gr.; 6,10 m) based on concentration of intravenously injected, fluorescently labeled molecules of increasing sizes (0.6 - 40000kD), in dissected and perfused brain homogenates. Expression of inflammatory activation markers for glia (IBA-1) and astrocytes (GFAP) in brain sections (n=2/gr.; 6,10 m) was assessed with confocal microscopy. Results: NOR test showed that Tgαq*44 mice compared to age matched controls are cognitively impaired based on decrease in recognition index (p=0.0002 at 6m and p=0.05 at 10m). Figure A illustrates progress in cognitive impairment in mice from 6th to 14th m (p=0.001). BBB permeability test revealed increased BBB damage in whole brain (p=0.001 at 6m) and in cortex and pons (respectively p=0.01 and 0.001 at 10m). Figure B illustrates activation of astrocytes (GFAP- red) and glia (IBA-1 -green) in 6m Tgαq*44 vs. FVB mice. Conclusions: We conclude that at early stages, HF induces VCI via mechanisms related to the impairment of BBB permeability and suggests that VCI precedes the development of clinical stage of HF. We also identify Tgαq*44 mice as a new model of naturally developing VCI with isolated HF and subsequent impairment of BBB permeability.

PKR Inhibition Rescues Memory Deficit and ATF4 Overexpression in ApoE ε4 Human Replacement Mice

Sporadic Alzheimer's disease (AD) is an incurable neurodegenerative disease with clear pathological hallmarks, brain dysfunction, and unknown etiology. Here, we tested the hypothesis that there is a link between genetic risk factors for AD, cellular metabolic stress, and transcription/translation regulation. In addition, we aimed at reversing the memory impairment observed in a mouse model of sporadic AD. We have previously demonstrated that the most prevalent genetic risk factor for AD, the ApoE4 allele, is correlated with increased phosphorylation of the translation factor eIF2α. In the present study, we tested the possible involvement of additional members of the eIF2α pathway and identified increased mRNA expression of negative transcription factor ATF4 (aka CREB2) both in human and a mouse model expressing the human ApoE4 allele. Furthermore, injection of a PKR inhibitor rescued memory impairment and attenuated ATF4 mRNA increased expression in the ApoE4 mice. The results propose a new mechanism by which ApoE4 affects brain function and further suggest that inhibition of PKR is a way to restore ATF4 overexpression and memory impairment in early stages of sporadic AD. Significance statement: ATF4 mRNA relative quantities are elevated in ApoE4 allele carriers compared with noncarrier controls. This is true also for the ApoE ε4 human replacement mice. ApoE4 mice injected with PKR inhibitor (PKRi) demonstrate a significant reduction in ATF4 expression levels 3 h after one injection of PKRi. Treatment of ApoE4 human replacement mice with the PKRi before learning rescues the memory impairment of the ApoE4 AD model mice. We think that these results propose a new mechanism by which ApoE4 affects brain function and suggest that inhibition of PKR is a way to restore memory impairment in early stages of sporadic AD.

Altered hippocampal information coding and network synchrony in APP-PS1 mice

β-amyloid is hypothesized to harm neural function and cognitive abilities by perturbing synaptic transmission and plasticity in Alzheimer's disease (AD). To assess the impact of this pathology on hippocampal neurons' ability to encode flexibly environmental information across learning, we performed electrophysiological recordings of CA1 hippocampal unit activity in AD transgenic mice as they acquired an action-reward association in a spatially defined environment; the behavioral task enabled the precise timing of discrete and intentional behaviors of the animal. We found that the proportion of behavioral task-sensitive cells in wild-type (WT) mice typically increased, whereas the proportion of place cells decreased with learning. In AD mice, this learning-dependent change of cell-discharge patterns was absent, and cells exhibited similar firings from the beginning to firings attained at the late learning stage in wild-type cells. These inflexible hippocampal representations of task and space throughout learning are accompanied by remarkable alterations of local oscillatory activity in the theta and ultra-fast ripple frequencies as well as learning abilities. The present data offer new insights into the in vivo cellular and network processes by which β-amyloid and other AD mutations may exert its harmful effects to produce cognitive and behavioral impairments in early stage of AD.

Cellular and network mechanisms underlying memory impairment induced by amyloid β protein.

It has long been known that amyloid ß protein (Aß) plays a key role in Alzheimer's Disease (AD) and in Down Syndrome cognitive decline. Recent findings have shown that soluble forms of Aß (mostly Aß oligomers; Aßo), rather than insoluble forms (fibrils and plaques), are associated with memory impairments in early stages of AD. Since synaptic plasticity and oscillatory network activity are required for memory formation, consolidation and retrieval, numerous attempts have been made to establish whether or not Aßo-induced alterations in synaptic plasticity and oscillatory network activity cause memory impairment. Despite a wealth of uncorrelated experimental evidence, such a relationship remains elusive. Furthermore, the specific cellular mechanisms underlying these disruptions remain to be determined. This review will discuss recent findings about the cellular and network mechanisms involved in Aßo-induced alterations of network oscillations and synaptic plasticity that could be responsible for the learning and memory impairments observed in early AD. Additionally, we will review some of the signal transduction pathways involved in these deleterious effects, which are revealing promising therapeutic targets to ease Aßo-induced brain dysfunction and treat AD.

Corrección neuropsicológica en las dificultades de la expresión y la comprensión del lenguaje

Objective. Language is a high level brain function that helps us communicate with each other, regulates our behavior, and organizes other brain functions. The purpose of this article is to present a case of a six year old boy with alteration of the expressive and receptive form of language, resulting from probable congenital factors. The main symptoms were incomprehensible speech, difficulties in following oral instructions, and learning disabilities. Method. Assessments, based on Luria’s methodology, were made before and after the application of the treatment. The assessment revealed kinesthetic, phonological and kinetic factor deficits. These results facilitated the creation and application of a structured intervention program, which was applied on a weekly basis, and consisted of activities of ascending levels of complexity, and which worked on different high level brain functions at the same time, all guided by the therapist. Results. The post test assessment showed the effectiveness of this program by reinforcing affected mechanisms and resulting in an increase of control over his verbal productions and comprehension of others. Conclusion. Language impairments in early stages of development could improve by using a program based on a neuropsychological assessment to generate and select the most appropriate activities to stimulate weak neuropsychological process, using those which are most appropriate.

Health-related quality of life and chronic obstructive pulmonary disease in early stages - longitudinal results from the population-based KORA cohort in a working age population.

BackgroundIt is widely recognized that health-related quality of life (HRQL) is impaired in patients with Chronic Obstructive Pulmonary Disease (COPD), but there is a lack of research on longitudinal associations of COPD and HRQL. This study examined the effects of COPD in early stages of disease on HRQL over ten years in a working-age general population setting in Southern Germany while considering the influence of common comorbidities.MethodsIn the population-based KORA F4 study (2006–08) 1,321 participants aged 41–61 years performed spirometry and reported information on HRQL (measured by the generic SF-12) and comorbidities. For the same participants, HRQL information was available seven years before and three years after the lung function test from the previous S4 (1999–2001) and the F4L follow-up study (2010). Using linear mixed models, the physical and mental component summary scores (PCS-12 / MCS-12) of the SF-12 were compared over time between COPD groups.Results7.8% of participants were classified as having COPD (according to the LLN definition and the Global Lungs Initiative), 59.4% of them in grade 1. Regression models showed a negative cross-sectional association of COPD grade 2+ with PCS-12 which persisted when comorbidities were considered. Adjusted mean PCS-12 scores for the COPD grade 2+ group were reduced (−3.5 (p = 0.008) in F4, −3.3 (p = 0.014) in S4 and −4.7 (p = 0.003) in F4L) compared to the group without airflow limitation. The size of the COPD effect in grade 2+ was similar to the effect of myocardial infarction and cancer. Over ten years, a small decline in PCS-12 was observed in all groups. This decline was larger in participants with COPD grade 2+, but insignificant. Regarding MCS-12, no significant cross-sectional or longitudinal associations with COPD were found.ConclusionDespite small HRQL differences between COPD patients in early disease stages and controls and small changes over ten years, our results indicate that it is important to prevent subjects with airflow limitation from progression to higher grades. Awareness of HRQL impairments in early stages is important for offering early interventions in order to maintain high HRQL in COPD patients.

Estradiol prevents olfactory dysfunction induced by A-β 25–35 injection in hippocampus

BackgroundSome neurodegenerative diseases, such as Alzheimer and Parkinson, present an olfactory impairment in early stages, and sometimes even before the clinical symptoms begin. In this study, we assess the role of CA1 hippocampus (structure highly affected in Alzheimer disease) subfield in the rats’ olfactory behavior, and the neuroprotective effect of 17 beta estradiol (E2) against the oxidative stress produced by the injection of amyloid beta 25–35.Results162 Wistar rats were ovariectomized and two weeks after injected with 2 μl of amyloid beta 25–35 (A-β25–35) in CA1 subfield. Olfactory behavior was evaluated with a social recognition test, odor discrimination, and search tests. Oxidative stress was evaluated with FOX assay and Western Blot against 4-HNE, Fluoro Jade staining was made to quantify degenerated neurons; all these evaluations were performed 24 h, 8 or 15 days after A-β25–35 injection. Three additional groups treated with 17 beta estradiol (E2) were also evaluated. The injection of A-β25–35 produced an olfactory impairment 24 h and 8 days after, whereas a partial recovery of the olfactory behavior was observed at 15 days. A complete prevention of the olfactory impairment was observed with the administration of E2 two weeks before the amyloid injection (A-β25–35 24 h + E2) and one or two weeks after (groups 8 A-β +E2 and 15 A-β +E2 days, respectively); a decrease of the oxidative stress and neurodegeneration were also observed.ConclusionsOur finding shows that CA1 hippocampus subfield plays an important role in the olfactory behavior of the rat. The oxidative stress generated by the administration of A-β25–35 is enough to produce an olfactory impairment. This can be prevented with the administration of E2 before and after amyloid injection. This suggests a possible therapeutic use of estradiol in Alzheimer’s disease.

Theory of mind in early psychosis

A deficit in theory of mind--the ability to infer and reason about the mental states of others - might underpin the poor social functioning of patients with psychosis. Unfortunately, however, there is considerable variation in how such a deficit is assessed. The current study compared three classic tests of theory of mind in terms of their ability to detect impairment in patients in the early stages of psychosis. Twenty-three patients within 2 years of their first psychotic episode and 19 healthy controls received picture-sequencing, joke-appreciation and story-comprehension tests of theory of mind. Whereas the picture-sequencing and joke-appreciation tests successfully detected a selective theory-of-mind deficit in patients, the story-comprehension test did not. The findings suggest that tests that place minimal demands on language processing and involve indirect, rather than explicit, instructions to assess theory of mind might be best suited to detecting theory-of-mind impairment in early stages of psychosis.

THU0393 Estimated Glomerular Filtration Rate is Associated with Bone Fragility in the Elderly

BackgroundOsteoporosis is frequently associated with renal disease, namely the bone metabolism disturbances caused by chronic kidney disease (CKD). Both diseases are highly prevalent in the elderly. The increased risk of...

Evaluation of speech impairment in early stages of Parkinson’s disease: a prospective study with the role of pharmacotherapy

Despite the initial reports showing beneficial effects of dopaminergic treatment on speech in Parkinson's disease (PD), more recent studies based upon valid measurements have not approved any improvement of speech performance under pharmacotherapy. The aim of this study was to analyze the effect of treatment initiation on the progression of speech impairment in PD, using novel evaluation criteria. Nineteen de novo patients with PD were tested and retested within 2years after the introduction of antiparkinsonian therapy. As controls, 19 age-matched individuals were recorded. Speech examination included sustained phonation, fast syllable repetition, reading text, and monolog. Quantitative acoustic analyses of the key aspects of speech based on Gaussian kernel distribution, statistical decision-making theory, and healthy speech observation were used to assess the improvement or deterioration of speech. A trend for speech performances to improve was demonstrated after treatment mainly in quality of voice, intensity variability, pitch variability, and articulation. The treatment-related improvement differed in various aspects of speech for individual PD patients. Improvements in vowel articulation and pitch variability correlated with treatment-related changes in bradykinesia and rigidity, whereas voice quality and loudness variability improved independently. Using a novel approach of acoustic analysis and advanced statistics, improvements in speech performance can be demonstrated in PD patients after the introduction of antiparkinsonian therapy. Moreover, changes in speech articulation and pitch variability appear to be related with dopaminergic responsiveness of bradykinesia and rigidity. Therefore, speech may be a valuable marker of disease progression and treatment efficacy in PD.

Atrial fibrillation (AF) and cognitive impairment in the elderly: A case–control study

AF is able not only to increase the risk of cognitive decline due to acute cerebrovascular events, but also to reduce cardiac output, with the consequence of impaired cerebral perfusion. The aim of this study was to evaluate the association between AF, dementia and depression in patients with negative anamnesis for past strokes. Our sample included 26 patients with a diagnosis of AF (paroxystic, persistent, permanent) and 31 patients with sinus rhythm, enrolled as controls. All selected patients underwent a Multidimensional Geriatric Assessment in order to investigate cognitive and behavioral functions. Statistical analysis of results showed a greater frequency of latent cognitive impairment in patients with AF, even in the absence of memory disorders. As a matter of facts, AF patients showed Mini Mental State Examination (MMSE) scores significantly lower than those with sinus rhythm (p<0.05) and Geriatric Depression Scale (GDS) scores higher than those without AF, evidencing a greater risk of depression too (p<0.02). Results showed a statistically significant association between AF, depression and cognitive impairment in early stage. In conclusion, AF is not only associated with the risk of developing cognitive impairment, but it can also be considered as a risk factor for dementia and depression, even in the absence of medical history of past stroke.

Cognitive impairment in early stages of multiple sclerosis

Cognitive dysfunction involves 40-65% of multiple sclerosis patients and can have a great functional impact. It can be detected in all the disease phenotypes since the early stages of the disease, and tends to progress over time. Memory, complex attention, information-processing speed and executive functions are most commonly involved. The relationship between cognitive changes and magnetic resonance imaging (MRI) findings may involve changes in different areas, including white matter lesions, cortical and deep grey matter and normal appearing brain tissue on conventional MRI. The search for effective therapeutic strategies is a major undertaking, involving the use of both pharmacologic and rehabilitative approaches. Early treatment with disease-modifying drugs that can contain the disease burden in the brain seems to be highly advisable in order to prevent or delay the development of cognitive impairment.

Comparison of Tissue Doppler Dynamics with Doppler Flow in Evaluating Left Atrial Appendage Function by Transesophageal Echocardiography in Prehypertensive and Hypertensive Patients

Increased blood pressure (BP) is associated with an increase in cardiovascular mortality and morbidity. We aimed to analyze the effect of increased BP onto the function of left atrial appendage (LAA) in early stages of hypertension. Transesophageal echocardiography (TEE) was prospectively performed to assess LAA functions in 120 patients with increased BP, and in 58 normotensive subjects without cardiovascular disease. Patients with increased BP were divided according to Joint National Committee VII (JNC VII) report: prehypertensive, stage-1 hypertensive and stage-2 hypertensive patients. During TEE, LAA late-emptying velocities (LAAEV) were significantly reduced only in stage-2 hypertensives as compared with control group (P < 0.001). In contrast, LAA late-contracting velocity (LAA TDI-D2) was significantly reduced in prehypertensive,stage-1 hypertensive and stage-2 hypertensive patients, when compared with control group (P < 0.05, P < 0.001, and P < 0.001, respectively). The LAA maximal areas were increased significantly only in stage-2 hypertensive patients when compared with control group (P < 0.05). During TEE, left atrial spontaneous echocardiographic contrast was found in 2 of 36 patients in prehypertension group, in 7 of 40 patients in stage-1 hypertension group, and in 10 of 44 patients in stage-2 hypertension group. Left atrial thrombi were observed in 3 (6.8%) patients of stage-2 hypertension group. In conclusion, in patients with untreated prehypertension and hypertension, elevation of afterload imposed on left atrium involved both left atrium and LAA, resulting in impairment of the LAA function. Tissue Doppler imaging (TDI) enables the detection of this functional impairment in early stages of hypertension, even in prehypertensive phase, when compared with conventional Doppler flow measurement of the LAA. Even in prehypertensive phase, BP should be decreased to normal levels to prevent the LAA dysfunction.