Development and preliminary validation of a virtual reality memory test for assessing visuospatial memory.

Background: Visuospatial memory impairment is a common symptom of Alzheimer's disease; however, conventional visuospatial memory tests are insufficient to fully reflect visuospatial memory impairment in daily life. Methods: To address patients' difficulties in locating and recalling misplaced objects, we introduced a novel visuospatial memory test, the Hidden Objects Test (HOT), conducted in a virtual environment. We categorized HOT scores into prospective memory, item free-recall, place free-recall, item recognition, and place-item matching scores. To validate the VR memory test, we compared HOT scores among individuals with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), and normal controls (NC), and also compared these scores with those of conventional neuropsychological tests. We tracked the participants' movement paths in the virtual environment and assessed basic features, such as total distance, duration, and speed. Additionally, we performed walking trajectory pattern mining such as outlier and stay-point detection. Results: We designed and implemented the HOT to simulate a house's living room and assess participants' ability to locate hidden objects. Our preliminary results showed that the total HOT score differed among 17 patients with AD, 14 with aMCI, and 15 NC (p < 0.001). The total HOT score correlated positively with conventional memory test scores (p < 0.001). Walking trajectories showed that patients with AD and aMCI wandered rather than going straight to the hidden objects. In terms of basic features, the total duration was significantly greater in AD than in NC (p = 0.008). In terms of trajectory pattern mining, the number of outliers, which were over 95% of the estimated trajectory, was significantly higher in AD than in NC (p = 0.002). The number of stay points, an index in which participants stayed in the same position for more than 2 s, was significantly higher in patients with AD and aMCI compared with NC (AD vs. NC: p = 0.003, aMCI vs. NC: p = 0.019). Conclusion: The HOT simulating real life showed potential as an ecologically valid test for assessing visuospatial memory function in daily life. Walking trajectory analysis suggested that patients with AD and aMCI wandered rather than going straight toward the hidden objects.

Behavioral Reserve in Behavioral Variant Frontotemporal Dementia.

"Reserve" refers to the individual clinical differences in response to a neuropathological burden. We explored the behavioral reserve (BR) and associated neural substrates in 40 participants with behavioral variant frontotemporal dementia (bvFTD) who were assessed with the frontal behavioral inventory (FBI) and magnetic resonance imaging. Because neuroimaging abnormality showed a high negative correlation with the FBI negative (but not positive) symptom scores, we developed a linear model only to calculate the nBR (BR for negative symptoms) marker using neuroimaging abnormalities and the FBI score. Participants were divided into high nBR and low nBR groups based on the nBR marker. The FBI negative symptom score was lower in the high nBR group than in the low nBR group having the same neuroimaging abnormalities. However, the high nBR group noted a steeper decline in cortical atrophy and showed less atrophy in the left frontotemporal cortices than the low nBR group. In addition, the fractional anisotropy (FA) values were greater in the high nBR than in the low nBR group, except in the sensory-motor and occipital areas. We identified an nBR-related functional network composed of bilateral frontotemporal areas and the left occipital pole. We propose the concept of BR in bvFTD, and these findings can help predict the disease progression.

Eye-Tracking Metrics for Figure-Copying Processes in Early- vs. Late-Onset Alzheimer's Disease.

Visuospatial dysfunction is a common symptom in patients with Alzheimer's disease (AD). To more focus on copying processes rather than on finally completed figures, we conceptually split the copying processes into three stages: visuoperceptual function, visuoconstructional function, and working memory function. We constructed perceptual and working spaces to investigate the different stages of copying, and then, we compared the number and duration of fixations and saccades and the number of switches across the two spaces. We used eye-tracking glasses to assess eye-tracking metrics in patients with early-onset AD (EOAD), patients with late-onset AD (LOAD), and normal control (NC) participants while they copied the simplified Rey-Osterrieth complex figure test (RCFT). Regarding eye metrics on the perceptual space, the number and duration of fixations were greater in both groups of patients with AD than in the NC participants group (number: EOAD vs. NC: p < 0.001, LOAD vs. NC: p = 0. 003/ duration: EOAD vs. NC: p < 0.001, LOAD vs. NC: p < 0.001). On the working space, the number and duration of fixations were greater in the patients with EOAD than in the patients with LOAD and NC participants (number: EOAD vs. LOAD: p = 0. 007, EOAD vs. NC: p = 0. 001/duration: EOAD vs. LOAD: p = 0. 008, EOAD vs. NC: p = 0. 002). The number of saccades and switching was higher in patients with EOAD than in NC participants (p < 0.001). The eye-tracking metrics from the simplified RCFT correlated with the neuropsychological test scores. Patients with EOAD and LOAD achieved the same level of performance at the simplified and original RCFT scores. However, patients with EOAD than LOAD showed a greater number and duration of fixations on the working space and more frequent switching between the perceptual and working spaces, which may reflect more cognitive efforts to achieve the same level of performance.

Standardization of the first Korean national reference standard for snake (Gloydius brevicaudus) antivenom.

In 2017, the second national reference standard (NRS) for Gloydius snake venom was established to replace the first NRS for Gloydius snake venom. In connection with the second venom NRS, a candidate for the first NRS for Gloydius snake antivenom was produced in 2017. In this study, the qualification of the candidate was estimated and the potency was determined by a collaborative study. The potency (anti-lethal titer and anti-hemorrhagic titer) of the candidate was determined by measuring the capability of the antivenom to neutralize the lethal and hemorrhagic effects of the second NRS for Gloydius snake venom, which was calibrated against the regional reference standard for Gloydius snake antivenom established in 2006. Two Korean facilities contributed data from 20 independent assays. Subsequently, one foreign national control research laboratories participated in this collaborative study. The general common potency of the anti-lethal and anti-hemorrhagic titers was obtained from the results of a total of 25 tests performed at three facilities. According to the results of the present study, the candidate preparation showed good quality and is judged to be suitable to serve as the first NRS for Gloydius snake antivenom with the following potency: an anti-lethal titer of 3100 unit (U) (95% confidence interval 2991-3276 U) and anti-hemorrhagic titer of 3000 U (95% confidence interval 2849-3159 U). In conclusion, the first NRS for Gloydius snake antivenom was established in this study. This reference standard will be used routinely for quality control of a snake antivenom product by manufacturer in Korea, which also can be used for national quality control, including a national lot-release test of the snake antivenom product.

A Validation Study of the Inbrain CST: a Tablet Computer-based Cognitive Screening Test for Elderly People with Cognitive Impairment.

BACKGROUND: Computerized versions of cognitive screening test could have advantages over pencil-and-paper versions by eliminating rater-dependent factors and saving the time required to score the tests and report the results. We developed a computerized cognitive screening test (Inbrain Cognitive Screening Test [Inbrain CST]) that takes about 30 minutes to administer on a touchscreen computer and is composed of neuropsychological tests already shown to be sensitive in detecting early cognitive decline in Alzheimer's disease (AD). The aims of this study were to 1) introduce normative data for Inbrain CST, 2) verify its reliability and validity, 3) assess clinical usefulness, and 4) identify neuroanatomical correlates of Inbrain CST. METHODS: The Inbrain CST runs on the Microsoft Windows 10 operating system and comprises 7 subtests that encompass 5 cognitive domains: attention, language, visuospatial, memory, and executive functions. First, we recruited 480 cognitively normal elderly people (age 50-90) from communities nationwide to establish normative data for Inbrain CST. Second, we enrolled 97 patients from our dementia clinic (26 with subjective cognitive decline [SCD], 42 with amnestic mild cognitive impairment [aMCI], and 29 with dementia due to AD) and investigated sensitivity and specificity of Inbrain CST for discriminating cognitively impaired patients from those with SCD using receiver operating characteristic (ROC) curve analyses. Third, we compared the Inbrain CST scores with those from another neuropsychological test battery to obtain concurrent validity and assessed test-retest reliability. Finally, magnetic resonance imaging (MRI)-based cortical thickness analyses were performed to provide anatomical substrates for performances on the Inbrain CST. RESULTS: First, in the normative sample, the total score on the Inbrain CST was significantly affected by age, years of education, and gender. Second, Inbrain CST scores among the three patient groups decreased in the order of SCD, aMCI, and AD dementia, and the ROC curve analysis revealed that Inbrain CST had good discriminative power for differentiating cognitively impaired patients from those with SCD. Third, the Inbrain CST subtests had high concurrent validity and test-retest reliability. Finally, in the cortical thickness analysis, each cognitive domain score and the total score of Inbrain CST showed distinct patterns of anatomical correlates that fit into the previously known brain-behavior relationship. CONCLUSION: Inbrain CST had good validity, reliability, and clinical usefulness in detecting cognitive impairment in the elderly. Furthermore, it showed neuroanatomical validity through MRI cortical thinning patterns. These results suggest that Inbrain CST is a useful cognitive screening tool with efficiency and validity to detect mild impairments in cognition in clinical settings.

A Comprehensive Evaluation of the Process of Copying a Complex Figure in Early- and Late-Onset Alzheimer Disease: A Quantitative Analysis of Digital Pen Data.

BACKGROUND: The Rey-Osterrieth Complex Figure Test (RCFT) is a neuropsychological test that is widely used to assess visual memory and visuoconstructional deficits in patients with cognitive impairment, including Alzheimer disease (AD). Patients with AD have an increased tendency for exhibiting extraordinary behaviors in the RCFT for selecting the drawing area, organizing the figure, and deciding the order of images, among other activities. However, the conventional scoring system based on pen and paper has a limited ability to reflect these detailed behaviors. OBJECTIVE: This study aims to establish a scoring system that addresses not only the spatial arrangement of the finished drawing but also the drawing process of patients with AD by using digital pen data. METHODS: A digital pen and tablet were used to copy complex figures. The stroke patterns and kinetics of normal controls (NCs) and patients with early-onset AD (EOAD) and late-onset AD (LOAD) were analyzed by comparing the pen tip trajectory, spatial arrangement, and similarity of the finished drawings. RESULTS: Patients with AD copied the figure in a more fragmented way with a longer pause than NCs (EOAD: P=.045; LOAD: P=.01). Patients with AD showed an increased tendency to draw the figures closer toward the target image in comparison with the NCs (EOAD: P=.005; LOAD: P=.01) Patients with AD showed the lower accuracy than NCs (EOAD: P=.004; LOAD: P=.002). Patients with EOAD and LOAD showed similar but slightly different drawing behaviors, especially in space use and in the initial stage of drawing. CONCLUSIONS: The digitalized complex figure test evaluated copying performance quantitatively and further elucidated the patients' ongoing process during copying. We believe that this novel approach can be used as a digital biomarker of AD. In addition, the repeatability of the test will delineate the process of executive functions and constructional organization abilities with disease progression.

A Collaborative Study to Establish the Second Korean National Reference Standard for Snake Venom.

In 2015, a candidate for the second national reference standard (NRS) of Gloydius snake venom was produced to replace the first NRS of Gloydius snake venom. In the present study, the potencies of the candidate were determined by a collaborative study, and the qualification of the candidate was estimated. The potencies of the candidate were determined by measuring the murine lethal titers and lapine hemorrhagic titers of venom against the regional working reference standard (RWRS) for antivenom using the methods described in the previous report for the first NRS of Gloydius snake venom. Three Korean facilities contributed data from a total of 30 independent assays. Subsequently, two foreign national control research laboratories contributed to this collaborative study. The results were calculated using the Reed-Muench method for lethality and determined using a mixed-effects model for hemorrhage. The general common potencies of the lethal and hemorrhagic titers were obtained from the results of the 30 tests performed at three Korean facilities. The results are expressed in micrograms for 1 test dose (TD) with a 95% confidence interval as follows: a lethal titer of 90.13 µg/TD (95% confidence interval = 87.39~92.86 µg) and a hemorrhagic titer of 10.80 µg/TD (95% confidence interval = 10.46~11.14 µg). In addition, the candidate preparation showed good quality evaluation according to the results of the quality estimation of the candidate and is judged to be suitable to serve as the Korean NRS for snake venom. In conclusion, the second NRS of Gloydius snake venom was established in this study and will be used for national quality control, including a national lot release test of Korean antivenom products.

Social Event Memory Test (SEMT): A Video-based Memory Test for Predicting Amyloid Positivity for Alzheimer's Disease.

Recent improvements in neuroimaging and molecular markers of Alzheimer's disease (AD) have aided diagnosis in the early stage of the disease, which greatly increases the chance for successful prevention and treatment. However, the expanding resources for AD diagnosis are unlikely to benefit all elderly due to economic burden. Here, we aimed to develop an inexpensive and sensitive method to detect early-stage AD. A scenario for real-world social event memory test (SEMT) was created and filmed in 360° video. Participants watched the 7-min video through head-mounted display (HMD) and then answered questionnaire about the video. We categorized the SEMT score into recall, recognition, and place-matching scores and compared them to scores on the Mini-Mental State Examination and Seoul Verbal Learning Test. Using the SEMT scores, we built a logistic regression model that discriminated between amyloid positivity and negativity of the participants, with a cross-validation AUC. Furthermore, a classifier was created using support vector machine, which produced 93.8-95.1% sensitivity in classifying individuals into four groups of normal, mild cognitive impairment with or without amyloid, and AD elderly. The high correlation between the SEMT score and amyloid positivity in individuals who experienced virtual social gathering through an HMD opens a new possibility for early diagnosis of AD.

Re-standardization of the Korean-Instrumental Activities of Daily Living (K-IADL): Clinical Usefulness for Various Neurodegenerative Diseases.

BACKGROUND AND PURPOSE: Evaluating instrumental activities of daily living (IADL) is an important part of procedure to diagnose dementia. The Korean-Instrumental Activities of Daily Living (K-IADL) has been used extensively in Korea. However, its cut-off score has not been reformulated since 2002. The purpose of this study was to yield a new optimal cut-off score for the K-IADL and confirm the validity of this new cut-off score with various dementia groups. METHODS: We retrospectively collected a total of 2,347 patients' K-IADL data from 6 general hospitals in Korea. These patients had mild cognitive impairment (MCI) or dementia with various etiologies for cognitive impairment. We also recruited a normal control group (n=254) from the community. Korean-Mini Mental State Examination, Short version of the Geriatric Depression Scale, Clinical Dementia Rating, and Global Deterioration Scale were administered to all participants. Caregivers completed K-IADL and Barthel Index. RESULTS: K-IADL scores were significantly different among dementia subgroups, but not significantly different among MCI subgroups. Based on internal consistency, correlations with other scales, and factor analysis, K-IADL showed excellent reliability and validity. The new optimal cut-off score to diagnose dementia was 0.40, which gave a sensitivity of 0.901 and a specificity of 0.916. Positive predictive value for dementia using the new cut-off score was 94.2% for Alzheimer's disease, 100% for vascular dementia, and 84% for Parkinson's disease. CONCLUSIONS: Our results illustrate that the new K-IADL cut-off score of 0.40 is reliable and valid for screening impairments of daily functioning resulting from various etiologies.

Tracking Cognitive Decline in Amnestic Mild Cognitive Impairment and Early-Stage Alzheimer Dementia: Mini-Mental State Examination versus Neuropsychological Battery.

BACKGROUND/AIMS: Although the Mini-Mental State Examination (MMSE), Clinical Dementia Rating-Sum of Boxes (CDR-SOB), and neuropsychological batteries are widely used for evaluating cognitive function, it remains elusive which instrument best reflects the longitudinal disease progression in amnestic mild cognitive impairment (aMCI) and probable Alzheimer disease (AD). We investigated whether changes in these three instruments over time correlate with loss of cortical gray matter volume (cGMV). METHODS: We retrospectively investigated 204 patients (aMCI, n = 114; AD, n = 90) who had undergone MMSE, CDR-SOB, the dementia version of the Seoul Neuropsychological Screening Battery (SNSB-D), and 3-dimensional T1-weighted magnetic resonance images at least twice. We investigated the partial correlation between annual decline in test scores and percent change of cGMV. RESULTS: In aMCI patients, changes in the SNSB-D total score (r = 0.340, p < 0.001) and CDR-SOB (r = 0.222, p = 0.020), but not MMSE, showed a correlation with cGMV loss, with the SNSB-D total score showing the strongest correlation. In AD patients, decline in all three test scores correlated significantly with cGMV loss, with MMSE exhibiting the strongest correlation (r = 0.464, p < 0.001). CONCLUSION: In aMCI patients, neuropsychological battery, though time-consuming, was the most adequate tool in tracking disease progression. In AD patients, however, MMSE may be the most effective longitudinal monitoring tool when considering cost-effectiveness.

Risk factors associated with domestic abuse directed at adults with disabilities in South Korea.

BACKGROUND: Most research on domestic abuse and disability has focused on women with disabilities, while research on abuse against men with disabilities and their risk factors is virtually non-existent. OBJECTIVE: The purpose of this research is to understand domestic abuse experienced by people with disabilities by investigating its prevalence and risk factors. METHOD: This research used the National Survey on Persons with Disabilities (2011). Using a stratified sampling method, 5259 respondents were identified to make up the final sample. Ordered logistic regression was used to verify risk factors for abuse. RESULTS: Risk factors for women with disabilities are age, educational attainment level, ADL, experiences of discrimination, awareness of disability discrimination, external support, and satisfaction with number of friends. Risk factors for men with disabilities are region, experiences of discrimination, awareness of disability discrimination, external support, and satisfaction with number of friends. For both women and men with disabilities, more experience of discrimination, greater awareness of disability discrimination, less external support, and less satisfaction with number of friends are associated with a higher likelihood of having experiences of abuse. Men with disabilities living in rural areas have a higher risk of abuse than those living in cities. Younger women, women with lower educational attainment, and those with lower physical functioning are more likely to have experienced abuse. CONCLUSIONS: Based on these findings, the authors make recommendations designed to protect people with disabilities from domestic abuse.

The neural correlates of motor intentional disorders in patients with subcortical vascular cognitive impairment.

Subcortical vascular cognitive impairment (SVCI) refers to cognitive impairment associated with small vessel disease. Motor intentional disorders (MID) have been reported in patients with SVCI. However, there are no studies exploring the neuroanatomical regions related to MID in SVCI patients. The aim of this study, therefore, was to investigate the neural correlates of MID in SVCI patients. Thirty-one patients with SVCI as well as 10 healthy match control participants were included. A "Pinch-Grip" apparatus was used to quantify the force control capabilities of the index finger in four different movement phases including initiation, development, maintenance, and termination. All participants underwent magnetic resonance imaging (MRI). Topographical cortical areas and white matter tracts correlated with the performances of the four different movement phases were assessed by the surface-based morphometry and tract-based spatial statistics analyses. Poorer performance in the maintenance task was related to cortical thinning in bilateral dorsolateral prefrontal, orbitofrontal and parietal cortices, while poorer performance in the termination task was associated with the disruption of fronto-parietal cortical areas as well as the white matter tracts including splenium and association fibers such as superior longitudinal fasciculus. Our study demonstrates that cortical areas and underlying white matter tracts associated with fronto-parietal attentional system play an important role in motor impersistence and perseveration in SVCI patients.

Improvement of hemispatial neglect by a see-through head-mounted display: a preliminary study.

BACKGROUND: Patients with right hemisphere damage are often unaware of, inattentive to and fail to interact with stimuli on their left side. This disorder, called hemispatial neglect, is a major source of disability. Inducing leftward ocular pursuit by optokinetic stimulation (OKS) relieves some of the signs of unilateral neglect. However, it is difficult to provide patients with a continuously moving background that is required for OKS. We studied whether OKS projected onto a see-through head-mounted display (HMD) would help treat neglect. METHODS: 14 patients with neglect after cerebral infarction performed line bisections on a computer screen, both with and without OKS that was either delivered by the HMD or on the same screen that was displaying the lines that were to be bisected. RESULTS: The line bisection performances were significantly different in the four conditions (P < 0.001). The post hoc analyses indicated that the rightward deviation observed in the control conditions on the line bisection tasks without OKS, improved significantly with the use OKS in both the HMD and screen conditions (α < 0.05). The results between the screen and HMD conditions were also different (α < 0.05). The OKS in the HMD condition corrected patients' rightward deviation more toward the actual midline than did the OKS provided during the screen condition. CONCLUSIONS: OKS projected onto the see-through HMD improved hemispatial neglect. The development of a portable device may aid in the treatment of neglect.

The Effects of Age, Gender, and Hand on Force Control Capabilities of Healthy Adults.

OBJECTIVE: The present study examined the effects of age (20s to 70s), gender (male and female), and hand (dominant and nondominant) on force control capabilities (FCCs) in four force control phases (initiation, development, maintenance, and termination). BACKGROUND: Normative data of FCCs by force control phase are needed for various populations in age and gender to identify a type of motor performance reduction and its severity. METHOD: FCCs of 360 participants (30 for each combination of age group and gender) were measured using a finger dynamometer and quantified in terms of initiation time (IT), development time (DT), maintenance error (ME), and termination time (TT). RESULTS: Although gradual increases (1%~28%) by age were shown in IT, DT, and TT, a dramatic increase in ME was observed among participants in their 50s (26%), 60s (68%), and 70s (160%) compared to those in their 20s~40s. The most distinctive interaction effect of age and gender was found in ME out of the four FCC measures. Lastly, hand and its related interactions were not found significant. CONCLUSION: Normative FCC data were established for four age groups (20s~40s, 50s, 60s, and 70s) and gender. APPLICATION: The normative FCC data can be used for evaluating an individual's motor performance, screening patients with brain disorders, and designing input devices triggered and/or operated by the finger.

Structural brain changes after traditional and robot-assisted multi-domain cognitive training in community-dwelling healthy elderly.

UNLABELLED: The purpose of this study was to investigate if multi-domain cognitive training, especially robot-assisted training, alters cortical thickness in the brains of elderly participants. A controlled trial was conducted with 85 volunteers without cognitive impairment who were 60 years old or older. Participants were first randomized into two groups. One group consisted of 48 participants who would receive cognitive training and 37 who would not receive training. The cognitive training group was randomly divided into two groups, 24 who received traditional cognitive training and 24 who received robot-assisted cognitive training. The training for both groups consisted of daily 90-min-session, five days a week for a total of 12 weeks. The primary outcome was the changes in cortical thickness. When compared to the control group, both groups who underwent cognitive training demonstrated attenuation of age related cortical thinning in the frontotemporal association cortices. When the robot and the traditional interventions were directly compared, the robot group showed less cortical thinning in the anterior cingulate cortices. Our results suggest that cognitive training can mitigate age-associated structural brain changes in the elderly. TRIAL REGISTRATION: ClnicalTrials.gov NCT01596205.

Directional and spatial motor intentional disorders in patients with right versus left hemisphere strokes.

OBJECTIVE: Motor intentional disorders (MIDs) are characterized by dysfunction in the preparation, initiation, maintenance, and termination of goal-oriented actions. In this study, we investigated (1) whether patients with right hemisphere strokes (RHS) and left hemisphere strokes (LHS) differ in the frequency of delayed action initiation (hypokinesia) and motor impersistence; (2) whether there is a directional or hemispatial component of hypokinesia or motor impersistence; (3) whether there is an association between the presence of hemispatial neglect and tests for MID; and (4) the location of injury associated with MID. METHOD: Thirty-two patients with acute unilateral stroke (21 with RHS and 11 with LHS) and 12 age-matched healthy controls participated in the study. To determine the presence and severity of directional and spatial hypokinesia and impersistence we used a new apparatus, the Directional Movement Tester (DMT). While being tested with the DMT, the participants held a static bar located either in the right or left hemispace using either their right or left hand and upon stimulus onset pushed the bar either leftward or rightward and maintained a given force for 10 sec. RESULTS AND CONCLUSION: The frequency of hypokinesia and impersistence was higher in the RHS group than in the LHS group, but there were no hypokinetic directional or spatial asymmetries. The RHS group did demonstrate left contralesional directional impersistence, but there were no spatial asymmetries of impersistence. Signs of hemispatial neglect were not associated with these measures of MID. Participants with frontal or subcortical lesions were significantly more likely to demonstrate hypokinesia and impersistence than those with posterior lesions.

Neurobehavioral dysfunction in patients with subcortical vascular mild cognitive impairment and subcortical vascular dementia.

Amnestic mild cognitive impairment (MCI) is considered to be a prodromal stage of Alzheimer's disease. Likewise, subcortical vascular MCI (svMCI) is considered as a prodromal stage of subcortical vascular dementia (SVaD). The objective of this study was to investigate neuropsychiatric features in patients with svMCI compared to healthy controls and patients with SVaD. We evaluated 31 patients with svMCI, 42 with SVaD, and 28 healthy controls who underwent neuropsychiatric assessments using the Neuropsychiatric Inventory (NPI) and the Frontal Behavioral Inventory (FBI). On both the NPI and FBI, SVaD patients had the most severe neuropsychiatric symptoms, followed by svMCI patients and then healthy controls, suggesting that svMCI might be a prodromal stage of SVaD in terms of neuropsychiatric abnormalities. When we compared the differences of mean scores between negative and positive symptoms in FBI, negative symptoms tended to be more predominant than positive symptoms in both svMCI and SVaD patients, but the tendency was stronger in SVaD patients than in svMCI patients. These results suggest that vascular cognitive impairment with small vessel disease would start with both negative and positive neuropsychiatric symptoms and progress to present more severe negative symptoms. These behavioral ratings may be useful for early detection of vascular cognitive impairment associated with small vessel disease.

The cortical neuroanatomy of neuropsychological deficits in mild cognitive impairment and Alzheimer's disease: a surface-based morphometric analysis.

Patients with probable Alzheimer's disease (AD) and the amnesic form of mild cognitive impairment (aMCI) often demonstrate several types of neuropsychological deficits. These deficits are often related to cortical atrophy, induced by neuronal degradation. The purpose of this study is to investigate whether different anatomic patterns of cortical atrophy are associated with specific neuropsychological deficits. The participants were 170 patients with AD and 99 patients with aMCI. All participants underwent the Seoul Neuropsychological Screening Battery (SNSB), which includes tests that assess attention, language, visuospatial functions, verbal and visual memory, and frontal/executive functions. Cortical atrophy (thinning) was quantified by measuring the thickness of the cortical mantle across the entire brain using automated, three-dimensional magnetic resonance imaging. The relationship between cortical thickness and neuropsychological performance was analysed using stepwise multiple linear regression analyses. These analyses (corrected P<.001) showed that several specific brain regions with cortical thinning were associated with cognitive dysfunction including: digit span backward, verbal and picture recall, naming and fluency, drawing-copying, response inhibition and selective attention. Some of the other functions, however, were not associated with specific foci of cortical atrophy (digit span forward, the word reading portion of the Stroop test, word and picture recognition). Our study, involving a large sample of participants with aMCI and AD, provides support for the postulate that cortical thinning-atrophy in specific anatomic loci are pathological markers for specific forms of cognitive dysfunction.

Line quadrisection errors in patients with hemispatial neglect.

Patients with left unilateral neglect misbisect lines toward the right. To discriminate between contralesional unawareness and ipsilesional hyperattention hypotheses for this ipsilesional bias, we performed the line quadrisection test on 18 patients with and 25 without neglect, and 24 normal controls. Overall the patients with neglect were unbiased when performing the left quadrisection task, but erred rightward on the right quadrisection task. These results suggest that the ipsilesional bisection errors produced by patients with neglect are primarily influenced by ipsilesional hyperattention rather than contralesional unawareness. However, further analyses showed heterogeneity of performance in left quadrisection, which can be explained by multiple factors that include the top down attention to left space associated with left quadrisection, the orienting to the salience of the line's left end, and distorted mental representation, in addition to ipsilesional hyperattention.

Attentional distractibility induced by optokinetic stimulation in mild cognitive impairment.

A recent study has shown that optokinetic stimulation (OKS) can induce attentional distractibility in Alzheimer disease (AD). In this study, we investigated whether OKS also perturbs balanced attentional deficit in patients with amnestic mild cognitive impairment (aMCI), a prodromal phase of AD, and explored whether the effects of OKS at baseline differ between aMCI patients who convert to AD at follow-up (converters) and those who do not (nonconverters). A total of 44 patients with aMCI, 14 patients with subcortical vascular mild cognitive impairment (svMCI), and 35 age-matched and education-matched normal controls were studied for their ability to bisect solid lines superimposed on a background of OKS. Background OKS movements were either leftward or rightward, or were stationary. A total of 33 of the 44 patients with aMCI were clinically followed for an average of 2.8 years, of which there were 15 converters and 18 nonconverters. Under both the leftward and rightward movement conditions, the magnitudes of line bisection errors (LBEs) in aMCI patients were greater than in normal controls. However, there were no differences in LBEs between svMCI patients and normal controls or between aMCI and svMCI patients. Baseline LBEs of aMCI converters were significantly greater than those of nonconverters in both leftward and rightward movement conditions. These results may indicate that OKS is useful for detecting AD at a very early stage and for predicting the conversion of aMCI to AD.