Mau-Sun Hua

Executive dysfunction and periventricular diffusion tensor changes in amnesic mild cognitive impairment and early Alzheimer's disease

Our aim in this study was to explore the neural substrates of executive function in frontal and nonfrontal white matter using diffusion tensor imaging (DTI). We studied the relationship between executive dysfunction and DTI measurements on 13 subjects with amnesic mild cognitive impairment (aMCI), 11 subjects with early Alzheimers disease (AD), and 16 control subjects. All participants underwent an examination of their intelligence, memory, and executive function and were subjected to DTI. Both aMCI and early AD subjects showed executive function impairment with differential performance in frontal‐related behaviors. Both aMCI and early AD subjects showed increased mean diffusivity in the genu of the corpus callosum and left frontal periventricular white matter (PVWM), whereas subjects with early AD showed an additional decrease in the fractional anisotropy of bilateral frontal PVWM and in the genu of the corpus callosum. The frontal PVWM was associated with performance on the Verbal Fluency Test, the Wisconsin Card Sorting Test (WCST), and Part B of the Trail Making Test. The parietal PVWM was associated with perseverative errors on the WCST and Part A of the Trail Making Test. In summary, executive function was impaired in subjects with aMCI and early AD and was associated with frontal and parietal PVWM changes. These changes may be due to early AD degeneration of the lateral cholinergic projections or to early change of the superior longitudinal fasciculus. Hum Brain Mapp, 2009.

Diffusion tensor changes in patients with amnesic mild cognitive impairment and various dementias

White matter damage and its contribution to clinical manifestations in patients with dementia have been increasingly recognized. To explore white matter changes in different types of dementia, we examined brain water diffusivity with diffusion tensor imaging (DTI). We measured fractional anisotropy and mean diffusivity of multiple white matter regions in patients with amnesic mild cognitive impairment (MCI, n=10), Alzheimers disease (AD, n=30), subcortical ischemic vascular dementia (SIVD, n=18), frontotemporal dementia (FTD, n=7), and control subjects (n=20). We performed pairwise comparisons in each region of interest between patients and controls. MCI patients showed diffusion tensor change (DTC) in the left anterior periventricular (PV) area, possibly in the right posterior PV area, and the genu of the corpus callosum. AD patients showed DTC in the corpus callosum, and in frontal and parieto-occipital subcortical and anterior PV areas. In SIVD patients, DTC occurred in the genu of the corpus callosum, and in bilateral frontal subcortical and PV areas. FTD patients differed from controls in showing DTC in the temporal and frontal subcortical areas, the genu of the corpus callosum and PV areas. The degree of DTC correlated with the clinical severity of dementia as assessed by the clinical dementia rating (CDR). Mean diffusivity was diffusely and positively associated with the CDR scores. Fractional anisotropy of the PV areas was negatively associated with the CDR scores, suggesting a critical role of the lateral cholinergic pathways.

Plasma tau as a window to the brain—negative associations with brain volume and memory function in mild cognitive impairment and early alzheimer's disease

Neurofibrillary tangles are associated with cognitive dysfunction, and hippocampal atrophy with increased CSF tau markers. However, the plasma tau levels of Alzheimers disease (AD) have not been well studied. We investigated plasma tau by using an immunomagnetic reduction assay in 20 patients with mild cognitive impairment (MCI) due to AD, 10 early AD dementia, and 30 healthy elders (HE). All received a 3D‐brain MRI scan and a set of cognitive function test. We explored their relationships with both brain structure and cognitive functions. Images were analyzed to determine the brain volumes and gray matter densities. Patients with MCI or early AD had significantly increased plasma tau levels compared with HE. Plasma tau levels were negatively associated with the performance of logical memory, visual reproduction, and verbal fluency; also negatively associated with volume of total gray matter, hippocampus, amygdala; and gray matter densities of various regions. Regression analyses indicated that logical memory explained 0.394 and hippocampus volume predicted .608 of the variance of plasma tau levels, both P < 0.001. Education years were negatively associated with the gray matter densities of the supramarginal (r = −0.407), middle temporal gyrus (r = −0.40) and precuneus (r = −0.377; all P < 0.05) in HE; and negatively associated with plasma tau levels in patients (r = −0.626). We propose that plasma tau may serve as a window to both structure and function of the brain. Higher education is a protective factor against AD and is associated with lower plasma tau levels in patients. Hum Brain Mapp 35:3132–3142, 2014.

Factor Structure and Age Effects with an Aphasia Test Battery in Normal Taiwanese Adults

This study was designed to explore in a Taiwanese sample the factor structure of an aphasia test battery composed of parts of several standardized aphasia tests. A secondary goal was to assess effects of normal aging on the obtained factors. The sample was 120 healthy Taiwanese adults, ranging in age from 30 to 78 years. Principal-components analysis of the aphasia test battery revealed 5 factors: verbal comprehension, effortful writing, word production, automatized writing, and visuomotor coordination skills. Because the latter 2 factors have common psychological features, they can be combined and reinterpreted as a factor on the mechanics of writing. Further data analysis with factor scores shows that aging unfavorably influences verbal comprehension, effortful writing processing, and word production functions.

Early clinical characteristics of patients with persistent post-concussion symptoms: A prospective study

Primary objective: To identify the early clinical features of patients with mild traumatic brain injury (mTBI) that are predictive of the presence of persistent post-concussion symptoms (PPCS). Research design: A prospective study was conducted at a level I trauma centre. Methods and procedures: One hundred and eighty mTBI patients participated in this study. The post-concussion symptoms (PCS) were evaluated with a PCS checklist. All patients were examined at 1, 2 and 8 weeks post-injury. The chi-square test was used to evaluate the associations of each PCS and the logistic regression was used to identify potential predictors of mTBI patients who might suffer from PPCS. Main outcomes and results: Less than one-tenth of the mTBI patients examined complained of PPCS at 2 months after head trauma. Patients with PPCS are more likely to suffer from intracranial lesions. Moreover, clinical symptoms at 1 and 2 weeks post-injury, especially physical ones including headache, dizziness and fatigue, were reported significantly more often by patients with PPCS. Conclusions: This study showed that early clinical symptoms and intracranial lesions may be strongly associated with the presence of PPCS. Thus, those specific characteristics may be used as early indicators of long-term difficulties.

New assay for old markers-plasma beta amyloid of mild cognitive impairment and Alzheimer's disease.

Although there is a consensus on the reduced levels of Aβ1-42 in the CSF of patients with AD, studies of plasma Aβ levels were inconsistent and have limited clinical value. We developed an immunomagnetic reduction assay (IMR) to determine the plasma levels of Aβ. We surveyed patients with varying AD severity (CDR = 0.5, n=16; CDR ≥ 1, n=18) and controls (n=26). Significant group differences were apparent in the levels of Aβ1-42 (F = 5.54, p = 0.002) and the Aβ1-42/Aβ1-40 ratio (F = 24.198, p < 0.001). Post-hoc analyses showed significant differences in the Aβ1-42 levels of controls and AD patients (p = 0.001) and in the Aβ1-42/Aβ1-40 ratio of control, MCI and AD subjects (all p ≤ 0.001). Regression analysis of Aβ1-42/Aβ1-40 ratios on dementia severity showed an adjusted R2 of 0.553 (p = 0.001). We identified a cut-off of 16.1 pg/ml for Aβ1-42 to differentiate control subjects from patients (both AD and MCI) with 85.3% sensitivity and 88.5% specificity. We also obtained a cut-off value of 0.303 for Aβ1-42/Aβ1-40 ratios with 85.3% sensitivity and 96.2% specificity. APOE 4 carriers had significantly higher Aβ1-42/Aβ1-40 ratios than the non-carriers (F = 4.839, p = 0.015). An independent group of case-control subjects validated both cut-off values for Aβ1-42/Aβ1-40 (100% sensitivity and 83.3% specificity) and for Aβ1-42 (100% sensitivity and 75.3% specificity). In a subgroup of longitudinal follow- up study, we found that the plasma Aβ was relatively stable with an interval of approximately 3 months. In conclusion, we found that the plasma Aβ1-42 is a useful biomarker for AD. The Aβ1-42/Aβ1-40 ratio improves the diagnostic power of the plasma Aβ biomarkers. The iron nanoparticles and IMR provides a novel method to measure plasma Aβ and could serve as an important clinical tool for the diagnosis of neurodegenerative diseases.

Chronic elemental mercury intoxication: neuropsychological follow-up case study

In initial and follow-up investigations of neuropsychological function in a patient with elemental mercury intoxication, his scores were compared with those of a group of normal control subjects matched for sex, age and education. Each subject received a comprehensive neuropsychological examination including a personality inventory. On the initial examination the results indicated that the patient had a significant depression of performance intellectual functioning, impairments of attention, non-verbal short-term memory and visual judgement of angles and directions, psychomotor retardation and personality changes including depression, anxiety, desire to be alone, lack of interest and sensitivity to physical problems. Such an impairment picture is compatible with the previous observations of individuals with chronic exposure to elemental, organic or inorganic mercury. The follow-up study was undertaken about 1.5 years later. The results show that the patients cognitive and personality functions were fully recovered. Our findings thus suggest a reversibility of impaired neuropsychological function in persons with elemental mercury poisoning if a prompt removal from the toxic environment is accomplished, together with proper medical treatment.

Age-related vulnerabilities along the hippocampal longitudinal axis.

Evidence for an anterior‐posterior gradient of age‐related volume reduction along the hippocampal longitudinal axis has been reported in normal aging, but functional changes have yet to be systematically investigated. The current study applied an advanced brain mapping technique, large deformation diffeomorphic metric mapping (LDDMM), automatically delineating the hippocampus into the anterior and posterior segments based on anatomical landmarks. We studied this anterior‐posterior gradient in terms of structural and functional MRI in 66 participants aged from 19 to 79 years. The results showed age‐related structural volume reduction in both anterior and posterior hippocampi, with greater tendency for anterior decrease. FMRI task contrasts that robustly activated the anterior (associative/relational processing) and posterior (novelty) hippocampus independently, showed only significant reduction of activation in the anterior hippocampus as age increased. Our results revealed positive correlation between structural atrophy and functional decrease in the anterior hippocampi, regardless of task performance in normal aging. These findings suggest that anatomy and functions related to the anterior hippocampus may be more vulnerable to aging, than previously thought. Hum Brain Mapp 33:2415–2427, 2012.

Neuropsychological performance and seizure-related risk factors in patients with temporal lobe epilepsy: A retrospective cross-sectional study

The aim of this study was to identify the neuropsychological features in patients with temporal lobe epilepsy (TLE) and their correlation with seizure-related variables. For this purpose, we carried out a retrospective analysis of data from 65 patients with TLE who had undergone a comprehensive neuropsychological assessment. The results suggest that the majority of patients with TLE were impaired in more than one cognitive domain, and among these patients, the mean proportions with defective semantic memory, language, motor/psychomotor speed, verbal episodic memory, and executive function were >50% each. Moreover, age at seizure onset was the strongest predictor of general intellectual impairment, and number of antiepileptic drugs and seizure frequency could significantly predict deficits in verbal memory, language, and psychomotor speed. However, epilepsy duration was a less potent predictor of cognitive deficit than has been reported in cross-sectional studies.

Cognitive dysfunction in early onset parkinsonism

Cognitive functions of 24 patients with early onset parkinsonism (age of onset before 40 years) and 24 controls were investigated by a battery of neuropsychological tests. Patients were shown to be impaired in performance IQ (PIQ), conceptual ability and regulation behavior, memory, visuospatial perception, and manual dexterity. Patients were also shown to have a higher Zung Depression score. However, analysis of the testing scores appeared to indicate that only a small portion of poor performance on neuropsychological tests are depression related. The results demonstrated that patients with early onset parkinsonism, in whom the factor of aging is not as important, still show cognitive dysfunction and suggested that Parkinsons disease itself can cause cognitive impairment