Ting-Wen Cheng

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.

rs5848 Variant of Progranulin Gene Is a Risk of Alzheimer’s Disease in the Taiwanese Population

Progranulin is the precursor of granulins, and its downregulation may lead to neurodegeneration. The single-nucleotide polymorphism rs5848 increases the risk of Alzheimer’s disease (AD). We explored the association between alleles of rs5848 and the risk of AD in the Taiwanese population. The frequency of the homozygous TT genotype (16.4 vs. 10.0%) increased in AD subjects by an odds ratio (OR) of 1.87 (p = 0.03) corrected for APOE Ε4, age and gender. Interaction between age and homozygous TT genotype accentuated the risk of AD (OR 4.44, p < 0.001). The homozygous TT genotype of rs5848 may play a role in the genetic risk of AD development, especially in the elderly.

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.

Microstructural Integrity of Cerebral Fiber Tracts in Hereditary Spastic Paraparesis with SPG11 Mutation

BACKGROUND AND PURPOSE: ARHSP-TCC is characterized by progressive leg spasticity, ataxia, and cognitive dysfunction. Although mutations in the human SPG11 gene were identified as responsible for ARHSP-TCC, the cerebral fiber integrity has not been assessed systemically. The objective of this study was to assess cerebral fiber integrity and its clinical significance in patients with ARHSP-TCC. MATERIALS AND METHODS: Five patients from 2 families who were clinically and genetically confirmed to have ARHSP-TCC were examined by neuropsychological evaluation and DSI of the brain. We performed voxel-based GFA analysis for global white matter evaluation, tractography-based analysis for tract-to-tract comparisons, and tract-specific analysis of the CST to evaluate microstructural integrity along the axonal direction. RESULTS: The neuropsychological evaluation revealed widespread cognitive decline across all domains. Voxel-based analysis showed global reduction of GFA in the cerebral white matter. Tractography-based analysis revealed a significant reduction of the microstructural integrity in all neural fiber types, while commissure and association fibers had more GFA reduction than projection fibers (P < .00001). Prefrontal and motor portions of the CC were most severely affected among all fiber tracts (P < .00001, P = .018). Tract-specific analysis of the CST validated a “dying-back” phenomenon (R2 = 0.68, P < .00001). CONCLUSIONS: There was a characteristic gradation in the reduction of microstructural integrity among fiber types and within the CC in patients with the SPG11 mutation. The dying-back process in CST might explain the pathogenic mechanisms for ARHSP-TCC.

Distinct Patterns and Clinical Implications of Semantic Memory Deterioration Among Patients With MCI.

Limited research has investigated the effects of executive dysfunction on semantic memory deterioration among patients with amnestic mild cognitive impairment (aMCI). This study examined the cognitive performance of 181 participants from various MCI subgroups, a group of mildly impaired individuals with dementia of the Alzheimer type (DAT) and a group of individuals with subjective memory impairment on various semantic memory tasks. The aMCI-single domain (aMCI-sd) group displayed poor performance on a semantic memory task requiring relatively higher degrees of effortful retrieval, and participants in the aMCI-multiple domain (aMCI-md) group, who also suffered with mild executive dysfunction displayed poor performance on all semantic memory tasks, similar to the DAT group. The nonamnestic MCI (non-a-MCI)-single domain group displayed normal performance across all semantic tasks, whereas the non-a-MCI-multiple domain group displayed a pattern similar to that of the aMCI-sd group. aMCI-sd patients who displayed poor performance on the semantic memory task had higher risk of conversion to DAT, whereas poor performance on tasks requiring relatively less effortful retrieval was associated with higher risk of conversion in the aMCI-md group. Thus, executive function may relate to deterioration of semantic memory retrieval processes. Such patterns of semantic memory impairment could be valuable for characterization of cognitive differences among MCI patients.

Diminution of context association memory structure in subjects with subjective cognitive decline

Alzheimers disease (AD) progresses insidiously from the preclinical stage to dementia. While people with subjective cognitive decline (SCD) have normal cognitive performance, some may be in the preclinical stage of AD. Neurofibrillary tangles appear first in the transentorhinal cortex, followed by the entorhinal cortex in the clinically silent stage of AD. We expected the earliest changes in subjects with SCD to occur in medial temporal subfields other than the hippocampal proper. These selective structural changes would affect specific memory subcomponents. We used the Family Picture subtest of the Wechsler Memory Scale‐III, which was modified to separately compute character, activity, and location subscores for episodic memory subcomponents. We recruited 43 subjects with SCD, 44 subjects with amnesic mild cognitive impairment, and 34 normal controls. MRI was used to assess cortical thickness, subcortical gray matter volume, and fractional anisotropy. The results demonstrated that SCD subjects showed significant cortical atrophy in their bilateral parahippocampus and perirhinal and the left entorhinal cortices but not in their hippocampal regions. SCD subjects also exhibited significantly decreased mean fractional anisotropy in their bilateral uncinate fasciculi. The diminution of cortical thickness over the mesial temporal subfields corresponded to brain areas with early tangle deposition, and early degradation of the uncinate fasciculus was in accordance with the retrogenesis hypothesis. The parahippocampus and perirhinal cortex contribute mainly to context association memory while the entorhinal cortex, along with the uncinate fasciculus, contributes to content‐related contextual memory. We proposed that context association and related memory structures are vulnerable in the SCD stage.

A single nucleotide TDP-43 mutation within a Taiwanese family: A multifaceted demon

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that typically presents as progressive behavioral changes or language deficits; and is associated with atrophy and hypometabolism in the frontal and temporal lobes. Amyotrophic lateral sclerosis (ALS) is a devastating degenerative disease that selectively involves upper and lower motor neurons. In recent years, these two neurodegenerative disorders have been found to share a common pathophysiological process, transactive response DNA binding protein 43 kDa (TDP-43) proteinopathy. Several mutations in the TARDBP (TAR DNA binding protein) gene have been shown to cause familial ALS (1,2), sporadic and familial FTLD-ALS (3,4), and pure FTLD (5,6). Here we report diverse clinical features of FTLD-ALS in three family members carrying a single missense mutation of the TARDBP gene.

Hippocampal atrophy but not white-matter changes predicts the long-term cognitive response to cholinesterase inhibitors in Alzheimer’s disease

P1-194 HIPPOCAMPAL ATROPHY BUT NOT WHITEMATTER CHANGES PREDICTS THE LONG-TERM COGNITIVE RESPONSE TO CHOLINESTERASE INHIBITORS IN ALZHEIMER’S DISEASE Yu-Wen Cheng, Ta-Fu Chen, Ting-Wen Cheng, Ya-Mei Lai, MauSun Hua, Ya-Fang Chen, Ming-Jang Chiu, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; College of Science, National Taiwan University, Taipei, Taiwan; Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan. Contact e-mail: yuwencheng610@gmail.com

Frontotemporal Dementia and Motor Neuron Disease: Report of 3 Cases in Taiwan and Literature Review

PURPOSE Case reports and a review of literature of the coexistence of motor neuron disease (MND) and frontotemporal dementia (FTD). CASE REPORT All three patients demonstrated generalized lower motor neuron signs and very few upper motor neuron signs. In the level of patterns of cognitive impairments, neuropsychological studies do not distinguish between patients with onset of weakness from bulbar palsy and patients with onset of weakness from limbs. All patients of FTD had their onset of MND or amyotrophic lateral sclerosis symptoms within a two-year interval which is similar to previous reports. FTD combined with MND may shorten the survival to less than three years shorter than cases with FTD only. Respiratory failure occurred one to two years after onset of the behavioral symptoms in all patients. CONCLUSION We reported three patients of FTD with MND to remind clinicians that these two disorders may occur together on the same patient and that these two disorders may belong to one broad spectrum neurodegenerative disease. KEYWORDS motor neuron disease, amyotrophic lateral sclerosis, frontotemporal dementia, frontotemporal lobar degeneration.