Chi-Wei Huang

Elevated basal cortisol level predicts lower hippocampal volume and cognitive decline in Alzheimer’s disease

Elevated glucocorticoid concentrations, decreased hippocampal volume and frontal atrophy with poor cognitive function have been reported in the elderly but not extensively in Alzheimers disease (AD). We enrolled 172 patients with AD over a 2-year follow-up period. Basal cortisol levels, biochemistry tests and mini-mental state examination (MMSE) scores were obtained and hippocampal and frontal atrophy were measured by CT scan for correlation. Basal plasma cortisol levels increased with age. Further, basal plasma cortisol levels were correlated with the radial width of the temporal horn, and elevated levels of plasma cortisol predicted a worse general cognitive performance. Higher plasma cortisol levels also correlated with rapid declines in MMSE scores after 2 years. Bilateral frontal atrophy showed no correlation with the above parameters. The relationship between high cortisol levels and hippocampal atrophy might adversely affect AD patients disproportionately, either in anatomical or cognitive function.

Validating the Chinese version of the Verbal Learning Test for screening Alzheimer’s disease

Episodic memory tasks are one of the most sensitive tools to discriminate Alzheimers disease (AD). This study aimed to validate a shorter version verbal memory test that will efficiently assess Chinese elderly with memory complaints. One hundred and eighty-five elderly with normal cognition (NC) and 217 AD patients were evaluated. Each participant received the Chinese Version Verbal Learning Test (CVVLT) consisting of 9 two-character nouns with 4 learning trials, 2 delayed recalls in 30 seconds and 10 minutes, and a word recognition test. In the NC elderly, age and sex had significant effects on recall scores in CVVLT, while education level showed an inverse correlation with 3 different patterns of errors made during the learning, recall, and recognition trials. AD patients had lower scores across all recall tests. In those with lower educational level, NC elderly had higher perseveration errors than AD patients. The cutoff value between the AD and NC groups in the 10-minute recall was 4/5 for those aged >75 years and 5/6 for those aged <75 years. This study has good validity in discriminating AD participants and the data here can help in diagnosing AD and mild cognitive impairment using the CVVLT.

Cognitive Severity-Specific Neuronal Degenerative Network in Charcoal Burning Suicide-Related Carbon Monoxide Intoxication: A Multimodality Neuroimaging Study in Taiwan

AbstractWhile carbon monoxide (CO) intoxication often triggers multiple intraneuronal immune- or inflammatory-related cascades, it is not known whether the pathological processes within the affected regions evolve equally in the long term. To understand the neurodegenerative networks, we examined 49 patients with a clinical diagnosis of CO intoxication related to charcoal burning suicide at the chronic stage and compared them with 15 age- and sex-matched controls. Reconstructions of degenerative networks were performed using T1 magnetic resonance imaging, diffusion-tensor imaging, and fluorodeoxyglucose positron emission tomography (PET). Tract-specific fractional anisotropy (FA) quantification of 11 association fibers was performed while the clinical significance of the reconstructed structural or functional networks was determined by correlating them with the cognitive parameters. Compared with the controls, the patients had frontotemporal gray matter (GM) atrophy, diffuse white matter (WM) FA decrement, and axial diffusivity (AD) increment. The patients were further stratified into 3 groups based on the cognitive severities. The spatial extents within the frontal-insular-caudate GM as well as the prefrontal WM AD increment regions determined the cognitive severities among 3 groups. Meanwhile, the prefrontal WM FA values and PET signals also correlated significantly with the patients Mini-Mental State Examination score. Frontal hypometabolic patterns in PET analysis, even after adjusted for GM volume, were highly coherent to the GM atrophic regions, suggesting structural basis of functional alterations. Among the calculated major association bundles, only the anterior thalamic radiation FA values correlated significantly with all chosen cognitive scores. Our findings suggest that fronto-insular-caudate areas represent target degenerative network in CO intoxication. The topography that occurred at a cognitive severity-specific level at the chronic phase suggested the clinical roles of frontal areas. Although changes in FA are also diffusely distributed, different regional changes in AD suggested unequal long-term compensatory capacities among WM bundles. As such, the affected WM regions showing irreversible changes may exert adverse impacts to the interconnected GM structures.

High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late‐onset lipid storage myopathy

Lan M‐Y, Fu M‐H, Liu Y‐F, Huang C‐C, Chang Y‐Y, Liu J‐S, Peng C‐H, Chen S‐S. High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late‐onset lipid storage myopathy.

Correlation among subcortical white matter lesions, intelligence and CTG repeat expansion in classic myotonic dystrophy type 1

Objectives –  To analyze the correlation among intelligence, brain magnetic resonance images (MRI) and genotype in classic myotonic dystrophy type 1 (DM1) patients.

Amyloid Burden in the Hippocampus and Default Mode Network: Relationships With Gray Matter Volume and Cognitive Performance in Mild Stage Alzheimer Disease

AbstractAmyloid load, as measured by florbetapir positron emission tomography (PET) standardized uptake value ratio (SUVr), has high specificity in the diagnosis of Alzheimer disease (AD). As the posterior cingulate cortex (PCC) represents densely amyloid-affected regions early in AD, we hypothesized that amyloid load within the key hubs of the default mode networks (DMN) may result in local or distant interconnected gray matter (GM) volume atrophy, thereby affecting cognitive performance. Thirty AD patients with a clinical dementia rating sum of box score ⩽2 were enrolled and underwent cognitive evaluation, 3-dimensional T1-weighted imaging and florbetapir PET. Volumes of interest (VOIs) included the hippocampus, lateral temporal region, and key hubs of the DMN [anterior cingulate cortex (ACC), PCC, posterior parietal, and precuneus]. The SUVr was calculated by florbetapir standard uptake value (SUV) within the T1-weighted image segmented GM VOIs divided by the cerebellar GM SUV. Our results suggested inverse correlations between ACC (&rgr; = −0.444, P = 0.016) and PCC SUVr (&rgr; = −0.443, P = 0.016) with PCC GM volume. In stepwise regression, the orientation scores were associated with PCC SUVr (&bgr; = 2.584, P = 0.02) and posterior parietal volume (&bgr; = −0.446, P = 0.04), whereas the word recall score was related to hippocampal volume (&bgr; = −0.391, P = 0.04). After removing the patients with a hippocampal VOI below the lowest tertile and adjusting for age, an inverse correlation was found between hippocampal volume and SUVr in the ACC (partial &sgr; = −0.639, P = 0.002), precuneus (partial &sgr; = −0.692, P = 0.002), and lateral temporal SUVr (partial &sgr; = −0.604, P = 0.005). Our results suggest that amyloid burden within the key DMN regions may contribute to local and distant GM atrophy, and that this may explain the cognitive scores.

Hyperhomocysteinemia in Alzheimer dementia patients and cognitive decline after 6 months follow-up period.

PURPOSE White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are commonly found in Alzheimers disease (AD) and may contribute to cognitive impairment. Plasma total homocysteine (tHcy) had also been linked with cognitive decline in AD. We examined the relationship among change of cognition, tHcy level, and WMHs on MRI in AD patients with a follow-up periods of 6 months. METHODS AD patients with normal creatinine level and initial clinical dementia rating (CDR) of 1 to 2 were enrolled. tHcy and biochemistry tests related to cerebral vascular risk factors were collected. WMHs were measured on MRI fluid attenuated inverse recovery sequence and classified into deep white matter hyperintensities (DWMHs) and periventricular white matter hyperintensities (PWMHs) by visual rating scale. Neuropsychological tests including cognitive ability screening instrument (CASI), mini-mental state examination (MMSE) converted from CASI scores and CDR were collected twice during the follow- up period of 6 months. RESULTS Ninety-two AD patients, 30 men and 62 women completed the study while the tHcy level was not significantly different between AD and age matched controls. tHcy level showed no correlation with CASI or MMSE score, at either the first or second examination. tHcy showed positive correlation with decline of CASI total score and abstract thinking (both p<0.01) but not in MMSE decline. There was no significant correlation between neuropsychiatric assessment and WMHs, but the decline of abstract thinking score was related to frontal PWMHs (R square=0.237, p=0.007). CONCLUSION tHcy might be associated with rapid cognitive decline in AD after a 6-month follow-up period and the effect might not be directly through WMHs. tHcy level correlated with greater WMHs in the trigone area although greater lesion load by MRI was in the occipital lobe.

Multi-parametric neuroimaging evaluation of cerebrotendinous xanthomatosis and its correlation with neuropsychological presentations

BackgroundCerebrotendinous xanthomatosis (CTX) is a rare genetic disorder. Recent studies show that brain damage in CTX patients extends beyond the abnormalities observed on conventional magnetic resonance imaging (MRI). We studied the MRI and 99 mTc-ethyl cysteinate dimer single photon emission computed tomography (SPECT) findings of CTX patients and made a correlation with the neuropsychological presentations.MethodsDiffusion tensor imaging (DTI) and 3D T1-weighted images of five CTX patients were compared with 15 age-matched controls. Voxel-based morphometry (VBM) was use to delineate gray matter (GM) and white matter (WM) volume loss. Fractional anisotropy (FA), mean diffusivity (MD), and eigenvalues derived from DTI were used to detect WM changes and correlate with neuropsychological results. SPECT functional studies were used to correlate with GM changes.ResultsCognitive results showed that aside from moderate mental retardation, the patient group performed worse in all cognitive domains. Despite the extensive GM atrophy pattern, the cerebellum, peri-Sylvian regions and parietal-occipital regions were correlated with SPECT results. WM atrophy located in the peri-dentate and left cerebral peduncle areas corresponded with changes in diffusion measures, while axial and radial diffusivity suggested both demyelinating and axonal changes. Changes in FA and MD were preceded by VBM in the corpus callosum and corona radiata. Cognitive results correlated with FA changes.ConclusionIn CTX, GM atrophy affected the perfusion patterns. Changes in WM included atrophy, and axonal changes with demyelination. Disconnection of major fiber tracts among different cortical regions may contribute to cognitive impairment.

Serum level and prognostic value of neopterin in patients after ischemic stroke.

BACKGROUND We hypothesized that serum level of neopterin is significantly predictive of prognostic outcome in patients after acute ischemic stroke (IS). METHODS Between November 2008 and May 2010, serum levels of neopterin were prospectively collected at 48 h after acute IS in 157 patients. RESULTS Serum neopterin levels were substantially higher in patients with severe neurological impairment [National institutes of Health Stroke Scale (NIHSS) score ≥12] than in those with NIHSS <12 (p<0.008). Furthermore, Spearmans test showed a strongly positive correlation between neopterin level and NIHSS (p=0.003). Multiple logistic regression analysis demonstrated that serum neopterin level was strongly and independently predictive of NIHSS ≥12 (p=0.002) at 48 h after acute IS and 90-day major adverse clinical outcome (defined as NIHSS≥12, recurrent stroke or death) (p=0.003). CONCLUSION Serum level of neopterin was notably increased after acute IS. This biomarker was strongly and independently predictive of 90-day unfavorable clinical outcome in patients after acute IS.

Patterns of executive dysfunction in amnestic mild cognitive impairment.

BACKGROUND Executive dysfunction is not uncommon in patients with amnestic mild cognitive impairment (aMCI). This study aimed to investigate the applicability of executive function tests (EFTs) in aMCI as an aid in establishing the diagnosis of multi-domain MCI. METHODS One hundred and twenty (120) aMCI patients, 126 Alzheimers disease (AD) patients, and 100 normal controls were enrolled. The EFTs evaluated included the trail making test, digit backward span, Stroop color-word test, and design fluency and category fluency tests. RESULTS Of the aMCI participants, 66% exhibited impairment in at least one EFT. Among the five selected EFTs, the category fluency test was the most discriminative in detecting executive dysfunction between patients with aMCI (standardized β = 0.264) or AD (standardized β = 0.361) with the controls, followed by the Stroop test. The performance of aMCI patients with two or more impaired EFTs was significantly different from those of controls but not from those of AD patients. CONCLUSION In the clinical setting, aMCI patients who fail in two or more EFTs may represent a unique population with multi-domain MCI that require close follow-up.