Higher Physical Activity Is Associated with Increased Attentional Network Connectivity in the Healthy Elderly.

The purpose of this study was to demonstrate the potential alterations in structural network properties related to physical activity (PA) in healthy elderly. We recruited 76 elderly individuals with normal cognition from Samsung Medical Center in Seoul, Korea. All participants underwent the Cambridge Neuropsychological Test Automated Battery and 3.0T brain magnetic resonance imaging (MRI). Participants were subdivided into quartiles according to the International Physical Activity Questionnaire scores, which represents the amount of PA. Through graph theory based analyses, we compared global and local network topologies according to PA quartile. The higher PA group demonstrated better performance in speed processing compared to the lower PA group. Regional nodal strength also significantly increased in the higher PA group, which involved the bilateral middle frontal, bilateral inferior parietal, right medial orbitofrontal, right superior, and middle temporal gyri. These results were further replicated when the highest and the lowest quartile groups were compared in terms of regional nodal strengths and local efficiency. Our findings that the regional nodal strengths associated with the attentional network were increased in the higher PA group suggest the preventive effects of PA on age-related cognitive decline, especially in attention.

Higher education affects accelerated cortical thinning in Alzheimer's disease: a 5-year preliminary longitudinal study.

BACKGROUND: Epidemiological studies have reported that higher education (HE) is associated with a reduced risk of incident Alzheimer's disease (AD). However, after the clinical onset of AD, patients with HE levels show more rapid cognitive decline than patients with lower education (LE) levels. Although education level and cognition have been linked, there have been few longitudinal studies investigating the relationship between education level and cortical decline in patients with AD. The aim of this study was to compare the topography of cortical atrophy longitudinally between AD patients with HE (HE-AD) and AD patients with LE (LE-AD). METHODS: We prospectively recruited 36 patients with early-stage AD and 14 normal controls. The patients were classified into two groups according to educational level, 23 HE-AD (>9 years) and 13 LE-AD (≤9 years). RESULTS: As AD progressed over the 5-year longitudinal follow-ups, the HE-AD showed a significant group-by-time interaction in the right dorsolateral frontal and precuneus, and the left parahippocampal regions compared to the LE-AD. CONCLUSION: Our study reveals that the preliminary longitudinal effect of HE accelerates cortical atrophy in AD patients over time, which underlines the importance of education level for predicting prognosis.

Shape changes of the basal ganglia and thalamus in Alzheimer's disease: a three-year longitudinal study.

BACKGROUND: A large number of Alzheimer's disease (AD) studies have focused on medial temporal and cortical atrophy, while changes in the basal ganglia or thalamus have received less attention. OBJECTIVE: The aim of this study was to investigate the existence of progressive topographical shape changes in the basal ganglia (caudate nucleus, putamen, and globus pallidus) and thalamus concurrent with AD disease progression over three years. This study also examined whether declines in volumes of the basal ganglia or thalamus might be responsible for cognitive decline in patients with AD. METHODS: Thirty-six patients with early stage AD and 14 normal control subjects were prospectively recruited for this study. All subjects were assessed with neuropsychological tests and MRI at baseline and Years 1 and 3. A longitudinal shape analysis of the basal ganglia and thalamus was performed by employing a boundary surface-based shape analysis method. RESULTS: AD patients exhibited specific regional atrophy in the right caudate nucleus and the bilateral putamen at baseline, and as the disease progressed, regional atrophic changes in the left caudate nucleus were found to conform to a distinct topography after controlling the total brain volume. Volumetric decline of the caudate nucleus and putamen correlated with cognitive decline in frontal function after controlling for age, gender, education, follow-up years, and total brain volume changes. CONCLUSION: Our findings suggest that shape changes of the basal ganglia occurred regardless of whole brain atrophy as AD progressed and were also responsible for cognitive decline that was observed from the frontal function tests.

Survival of Alzheimer's disease patients in Korea.

BACKGROUND/AIMS: The natural history of Alzheimer's disease (AD) has rarely been studied in the Korean population. Our study on survival analyses in Korean AD patients potentially provides a basis for cross-cultural comparisons. METHODS: We studied 724 consecutive patients from a memory disorder clinic in a tertiary hospital in Seoul, who were diagnosed as having AD between April 1995 and December 2005. Deaths were identified by the Statistics Korea database. The Kaplan-Meier method was used for survival analysis, and a Cox proportional hazard model was used to assess factors related to patient survival. RESULTS: The overall median survival from the onset of first symptoms and from the time of diagnosis was 12.6 years (95% confidence interval 11.7-13.4) and 9.3 years (95% confidence interval 8.7-9.9), respectively. The age of onset, male gender, history of diabetes mellitus, lower Mini-Mental State Examination score, and higher Clinical Dementia Rating score were negatively associated with survival. There was a reversal of risk of AD between early-onset and later-onset AD, 9.1 years after onset. CONCLUSIONS: The results of our study show a different pattern of survival compared to those studies carried out with western AD populations. Mortality risk of early-onset AD varied depending on the duration of follow-up.

Changes in subcortical structures in early- versus late-onset Alzheimer's disease.

Patients with early-onset Alzheimer's disease (EOAD) are reported to be different from those with late-onset Alzheimer's disease (LOAD) in terms of neuropsychological and neuroimaging findings. In this study, we aimed to compare the longitudinal volume changes of 6 subcortical structures (the amygdala, hippocampus, thalamus, putamen, globus pallidus, and caudate nucleus) between patients with EOAD and LOAD for 3 years. We prospectively recruited 36 patients with probable Alzheimer's disease (14 EOAD, 22 LOAD) and 14 normal control subjects. We analyzed the volume of subcortical structures using an automatic surface-based method. At baseline, there were no differences in the volumes of subcortical structures between patients with EOAD and LOAD. However, over 3 years of longitudinal follow-up, patients with EOAD showed more rapid volumetric decline in the caudate, putamen, and thalamus than patients with LOAD, which is consistent with neuropsychological results. Our findings suggested that the cognitive reserve theory might be applicable to explain different decline rates of the volumes of the basal ganglia and thalamus according to onset age.

Longitudinal changes of cortical thickness in early- versus late-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) has been shown to progress more rapidly than late-onset Alzheimer's disease (LOAD). However, no studies have compared the topography of brain volume reduction over time. The purpose of this 3-year longitudinal study was to compare EOAD and LOAD in terms of their rates of decline in cognitive testing and topography of cortical thinning. We prospectively recruited 36 patients with AD (14 EOAD and 22 LOAD) and 14 normal controls. All subjects were assessed with neuropsychological tests and with magnetic resonance imaging at baseline, Year 1, and Year 3. The EOAD group showed more rapid decline than the LOAD group in attention, language, and frontal-executive tests. The EOAD group also showed more rapid cortical thinning in widespread association cortices. In contrast, the LOAD group presented more rapid cortical thinning than the EOAD group only in the left parahippocampal gyrus. Our study suggests that patients with EOAD show more rapid cortical atrophy than patients with LOAD, which accounts for faster cognitive decline on neuropsychological tests.

The effects of small vessel disease and amyloid burden on neuropsychiatric symptoms: a study among patients with subcortical vascular cognitive impairments.

Neuropsychiatric symptoms (NPS) affect the quality of life of patients with dementia and increase the burden on caregivers. We aimed to evaluate how small vessel disease (SVD) such as lacunae or white matter hyperintensities (WMH), and amyloid burden affect NPS. We recruited 127 patients with subcortical vascular cognitive impairment who were assessed with brain magnetic resonance imaging, Pittsburgh compound-B (PiB) positron emission tomography and the neuropsychiatric inventory (NPI). To explore the association between lacunae, WMH, or PiB retention ratio and NPS, we performed multivariate regression analysis after controlling for possible confounders. Each additional lacuna, especially in the frontal region, was associated with higher odds of depression, apathy, aberrant motor behavior, nighttime behavior, appetite changes, and higher score of total NPI; larger WMH volume, especially in the frontal region, was associated with higher odds of apathy and higher score of total NPI. Furthermore, for the effects of lacunae or WMH on total NPI score we set Clinical Dementia Rating Sum of Boxes as the mediator. Greater PiB retention ratio was associated with higher odds of delusions and irritability. The SVD and amyloid pathologies did not show interactive effects on NPS. Our findings suggested that SVD and amyloid burden independently affected specific NPS.

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.

Survival in frontotemporal lobar degeneration in a Korean population.

Frontotemporal lobar degeneration (FTLD) can be subdivided into frontotemporal dementia (FTD), FTD combined with motor neuron disease (FTD-MND), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). FTLD has been considered a rare disorder, and its' demographic and survival data have rarely been studied in Asian population. A survival analysis using the Kaplan-Meier method was performed for 121 consecutive patients with clinically diagnosed FTLD who attended the Memory Disorder Clinic at Samsung Medical Center in Seoul, Republic of Korea, between January 1995 and September 2006. The overall median survival from the onset of the first symptom was 9.6 years (95% CI=8.3-10.8 y). The survival was shortest in FTD-MND (3 y) and longest in SD (11.3 y). The median survival time of FTD (9.8 y) was shorter than that of SD and longer than that of FTD-MND and PNFA. The use of the Cox proportional-hazards model to examine the effect of demographics on survival revealed that only age at onset was associated with survival. In general, our data are comparable with those from the Western countries. However, the female proportion was greater across all subtypes of FTLD and the survival of patients with PNFA was shorter than those of other groups.

Hanja (Ideogram) alexia and agraphia in patients with semantic dementia.

Posterior fusiform gyrus (BA 37) is responsible for Hanja (ideogram) alexia in stroke patients. Patients with semantic dementia (SD) have lesions in the basal temporal area. The close proximity in these two lesions and the fact that reading ideograms requires holistic processing as is necessary in recognition of objects, suggests a possibility that ideogram alexia/agraphia may occur in patients with SD. We established and carried out Hanja and Hangul (phonogram) reading/writing tasks on six SD patients and nine Alzheimer's disease (AD) patients as control to see if these two patient groups show dissociation in the two sets of tests. SPM analysis was performed on the SD patients' PET images to look for any dysfunctions in the posterior fusiform gyrus. The SD patients manifested Hanja alexia/agraphia whereas Hangul reading/writing ability was relatively preserved. There were group differences between SD and AD in the Hanja tasks but not in the Hangul tasks. The SPM analysis revealed no hypometabolism in the posterior fusiform gyrus, but only in the middle and the anterior part of the temporal gyrus. Dysfunction in the middle temporal gyrus (BA 21) may have disrupted the temporal lobe connections preventing the function of the posterior fusiform gyrus.

18F-FDG PET findings in frontotemporal dementia: an SPM analysis of 29 patients.

UNLABELLED: Frontotemporal dementia (FTD) is a common cause of presenile dementia. The aim of the current study was 2-fold: (a) to delineate the brain regions with reduction of glucose metabolism, and (b) to investigate the hemispheric asymmetry of glucose metabolism in FTD using (18)F-FDG PET. METHODS: We compared the regional metabolic patterns on (18)F-FDG PET images obtained from 29 patients with FTD and 11 healthy subjects using a voxel-wise analysis (statistical parametric mapping [SPM]). The hemispheric asymmetry of glucose metabolism was computed based on 2 different measures: one (AI(ROI)) by counting the (18)F-FDG activity of each hemisphere on the normalized and spatially smoothed PET images and the other (AI(SPM)) by counting the number of voxels with significant hypometabolism based on SPM results. RESULTS: Significant hypometabolism was identified in extensive prefrontal areas, cingulate gyri, anterior temporal regions, and the left inferior parietal lobule. Hypometabolism was also found in the bilateral insula and uncus, left putamen and globus pallidus, and medial thalamic structures. Frontal hypometabolism was more prominent in the left hemisphere than in the right. Twenty-six (90%) of the 29 patients with FTD had AI(ROI) values indicating significant lateralization of glucose metabolism; 18 patients had hypometabolism more severe on the left than right side, and only 8 patients had the opposite pattern. Results from AI(SPM) showed similar patterns. CONCLUSION: The voxel-wise analysis of (18)F-FDG PET images of patients with FTD revealed hypometabolism in extensive cortical regions, such as frontal and anterior temporal areas, cingulate gyri, uncus, and insula and subcortical areas, including basal ganglia (putamen and globus pallidus) and medial thalamic regions. The hemispheric asymmetry of hypometabolism (more frequently lateralized to the left) was common in patients with FTD, which may be another metabolic feature that helps to differentiate FTD from Alzheimer's disease or other causes of dementia.

The Closing-in Phenomenon in Alzheimer's Disease and Vascular Dementia.

BACKGROUND AND PURPOSE: The closing-in phenomenon is the tendency to draw near or on the target when copying figures, which has been found mostly in patients with Alzheimer's disease (AD). We attempted to quantify the degree of closing-in and to compare it between patients with AD and vascular dementia (VaD). METHODS: The subjects (55 AD, 39 VaD and 38 normal controls) were asked to copy the figure of alternating square and triangle, starting at the designated point and continuing from left to right. The patients with AD and VaD did not differ in age, education, severity of dementia or Rey Complex Figure Test copy score. The proximity (Y-axis) of the subject's drawing to the target was plotted at intervals of 2 mm along the X-axis and the degree of closing-in was computed from the slope of the regression line. RESULTS: The AD and VaD patients showed a steeper slope than the controls. There was no significant difference, however, in the magnitude of closing-in of the AD and VaD patients. When closing-in was defined as a slope that was greater than the mean+2SD of the slope observed for the controls, 32.7% of the AD and 25.6% of the VaD patients showed closing-in. CONCLUSIONS: Our study, using a new method of measuring the degree of closing-in, suggests that this phenomenon is not specific to AD.

The influence of illusory motion on line bisection performance in normal subjects.

The present study examines whether illusory movement (IM) of a horizontal line, induced by a moving background (MB), influences line-bisection performance in normal subjects. The first experiment attempted to identify the speeds of MB that induce IM. We found that when speed is increased from 1.53 degrees to 13.3 degrees/sec, IM increases, but that with further speed increases, IM decreases. Leftward MB induces rightward IM, and vice versa. In the second experiment, we had subjects bisect lines at MB speeds that had been shown to induce IM in the first experiment. We found that leftward MB induced a rightward bias, and vice versa. We also found that there was a relationship between the magnitude of IM and the degree of bias. In the third experiment, by making the target line larger than the MB, we made the conditions where IM was presumably absent. Unlike the results of bisection performed with IM, subjects showed a bias in the direction of the MB. Overall, these experiments demonstrated that the perception of motion induces subjects to attend in the direction of movement.

Pseudoneglect in solid-line versus character-line bisection tasks: a test for attention dominance theory.

OBJECTIVE: Normal subjects tend to bisect lines slightly to the left of the true midpoint, a phenomenon termed pseudoneglect. To test whether pseudoneglect relates to the right hemisphere's dominance for spatial attention or to the hemispheric difference in processing global-local stimulus properties, we administered conventional solid-line (SBT) and novel character-line (CBT) bisection tasks to normal subjects of different ages. METHODS: Normal subjects, consisting of 40 young and 40 older individuals, received 3 experimental tasks, a standard SBT and 2 types of CBT. Each subject completed 10 consecutive trials of each task presented in counterbalanced order between subjects. RESULTS: Across age groups, deviations on CBT were further to the right than those of SBT, and the leftward bias (pseudoneglect) was significant only in SBT. CONCLUSION: These results indicate that the bisection errors in normal subjects depend on the characteristics demanded by the specific task. Thus, our findings argue against the attention dominance theory and support a "task specificity" theory for pseudoneglect.

Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI).

The Neuropsychiatric Inventory (NPI) is used to assess neuropsychiatric symptoms in dementia patients. To reduce clinicians' time taken to administer the NPI, the authors studied a caregiver-administered NPI (CGA-NPI), in which caregivers completed the written form of the NPI worksheet. After a brief presupervision session, the caregivers of 61 dementia patients completed the CGA-NPI by reading through the worksheet. This was followed by a postsupervision session to check if the caregivers had completed the form appropriately. The correlation between the prevalence rates of each neuropsychiatric symptom obtained by the CGA-NPI and those obtained by the NPI was fair to good (kappa = 0.57-0.90) in all domains. All frequency, severity, and caregivers' distress scores of the CGA-NPI correlated significantly with those of the NPI (r> 0.6, P<.001). Total CGA-NPI scores also correlated highly with total NPI scores (r= 0.86, P<.001). These results suggest that the CGA-NPI can substitute for the NPI, saving administration time.

Visual search pattern during the line quadrisection task in normal subjects.

A common test for the assessment of hemispatial neglect is the line bisection test. A recent modification of the task has been reported wherein subjects place a mark at either 25% or 75% of line length ('quadrisection'). In a previous study, we suggested that line quadrisection might entail iteration of two steps involved in standard line bisection: (1) finding the midpoint of the entire line, and then (2) bisecting the half-line segment between the adjudged midpoint and the line end ipsilateral to the target quadrisection point. The present study investigated eye movement patterns during line quadrisection in order to test this hypothesis. Twenty normal volunteers determined the left or right quadrisection point of a horizontal line while their eye movements were recorded using two-dimensional video-oculography. Analysis revealed that, like the results of previous studies on bisection, most normal subjects fixate the central portion of the line segment before reaching the target area during the quadrisection task. Normal subjects' eye movements during quadrisection performance share a number of features with line bisection and provide support for the two-step processing hypothesis.

Mechanism of the closing-in phenomenon in a figure copying task in Alzheimer's disease patients.

The"closing-in phenomenon"in figure copying tasks refers to a tendency to copy near the target, or to overlap the target to be copied. The mechanisms underlying the closing-in phenomenon have not been fully elucidated. We posit that closing-in may be related to the patients'compensatory strategies to overcome visuospatial dysfunction or visuospatial working memory deficit. Thus, it is expected that as the complexity of the target figure or the distance from the target to the copying space is increased, the magnitude of closing-in will be increased. Thirteen patients with Alzheimer's disease (AD) who demonstrated closing-in on a screening test and 15 healthy controls participated in this study. Each subject copied figures in conditions that varied in terms of figure complexity and distance from the target to the copying space. Neither figure complexity nor distance between the target and copying space affected the degree of closing-in in normal subjects. In contrast, in AD patients, the magnitude of closing-in increased as a function of figure complexity; however closing-in was unchanged by varying the distance from the target to the copying space. Our results suggest that copying near the target figure might be the patients'strategy to compensate for their visuospatial dysfunction or visuospatial working memory deficits.

Validation of the Korean version of the Bayer activities of daily living scale.

The Bayer-activities of daily living (B-ADL) is a brief and internationally applicable ADL instrument which has been validated in three European countries. The B-ADL has been developed to provide a tool for the assessment of functional deficits in performance of every day tasks as they are observed in mild to moderate stages of dementia. The B-ADL has been constructed for use in clinical trials as well as in clinical practice. From an international perspective the major application is the evaluation of treatment effects in clinical studies and the current study was to validate the Korean version of the B-ADL. The B-ADL was administered to a total of 129 subjects with varying degrees of cognitive decline. A substantial cross-sectional correlation between B-ADL and MMSE scores was found. The internal consistency of B-ADL was above 0.98. A factor analysis revealed that a one factor solution accounted for most of the total variance. The B-ADL global score significantly increased as the severity of dementia, assessed by global deterioration scale increased from stage 1 to 5. Test-retest reliabilities of B-ADL global score and each item were very high. All of these results were very similar to those from three European countries except for the proportion of 'non-applicability' in some ADL items. These findings provide evidence that the Korean version of B-ADL can be useful not only for clinical purposes but also for international multicentre studies.

Manual approach during hand gesture imitation.

BACKGROUND: Patients' tendency to draw near or into the target when copying figures, a phenomenon termed closing-in, has been previously described. That the closing-in could occur when copying hand gestures has also been noted. OBJECTIVES: To study a patient with corticobasal degeneration to quantify his manual approach behavior and to test a possible working memory hypothesis. METHODS: The subject of this study is a patient with severe ideomotor apraxia from probable corticobasal degeneration. Fluorine 18-labeled deoxyglucose-positron emission tomographic findings revealed a hypometabolism involving the bilateral parietotemporal and the right frontal lobes. When asked to copy an examiner's (J.C.K.) hand gesture, the patient approached, touched, or grasped the examiner's hand, a behavior mostly consistent with the closing-in behavior previously proposed. To investigate the frequency and severity of closing-in, the patient was asked to copy 20 meaningless hand gestures (10 simple and 10 complex). Copying the 20 hand gestures was performed with either the left or the right hand while the patient was seated opposite the examiner (across condition) or on the same side of the examiner (lateral condition). RESULTS: Of the 80 trials, closing-in occurred in 43 (53.8%) (35 with approaching, 6 with touching, and 2 with grasping). The closing-in was more frequent and more severe when gesturing with the left than the right hand, but it did not differ between the lateral and across conditions and between simple and complex gestures. CONCLUSIONS: Corticobasal degeneration might be associated with aberrant manual approach behavior. Although our results do not support the working memory hypothesis, frontal dysfunction might have led to a loss of voluntary control of ontologically primitive propensity to move the forelimb in the direction to which one attends.