Modest Overweight and Healthy Dietary Habits Reduce Risk of Dementia: A Nationwide Survey in Taiwan.

BACKGROUND: Evidence of the associations of dietary habits and body mass index with dementia is inconsistent and limited in East Asian countries. OBJECTIVE: We aim to explore the associations of dietary habits and body mass index with the odds of dementia. DESIGN: Cross-sectional observational study. SETTING: A nationwide, population-based, door-to-door, in-person survey. PARTICIPANTS: Selected by computerized random sampling from all 19 counties in Taiwan. MEASUREMENT: Diagnosis of dementia using the criteria recommended by the National Institute on Aging-Alzheimer's Association. Lifestyle factors, dietary habits and demographic data were compared between normal subjects and participants with dementia. RESULTS: A total of 10432 residents were assessed, among whom 2049 were classified as having a mild cognitive impairment (MCI), 929 were diagnosed with dementia, and 7035 were without dementia or MCI. After adjustment for age, gender, education, body mass index (BMI), dietary habits, habitual exercises and co-morbidities, including hypertension, diabetes and cerebrovascular diseases, we found inverse associations of dementia with the consumption of fish (OR 0.62, 95% CI 0.41-0.94), vegetables (OR 0.35, 95% CI 0.13-0.95), coffee (OR 0.59, 95% CI 0.35-0.97), green tea (OR 0.51, 95% CI 0.34-0.75) and other types of tea (OR 0.41, 95% CI 0.28-0.60). There was no association between dementia and fruit consumption. Compared with people who had a normal BMI (18 < BMI <= 24), older overweight people (24 < BMI <=30) had a reduced risk of dementia with an adjusted OR of 0.77 (95% CI 0.61-0.96). CONCLUSIONS: Our study provides preliminary evidence that suggests that the consumption of fish, vegetables, tea, and coffee has potential benefits against dementia in East Asian population. Being modestly overweight (nadir risk at BMI = 25) in late life was associated with decreased odds of dementia. The benefit of fruits may be offset by their high sugar content.

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 Aß1-42 in the CSF of patients with AD, studies of plasma Aß levels were inconsistent and have limited clinical value. We developed an immunomagnetic reduction assay (IMR) to determine the plasma levels of Aß. 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 Aß1-42 (F = 5.54, p = 0.002) and the Aß1-42/Aß1-40 ratio (F = 24.198, p < 0.001). Post-hoc analyses showed significant differences in the Aß1-42 levels of controls and AD patients (p = 0.001) and in the Aß1-42/Aß1-40 ratio of control, MCI and AD subjects (all p ≤ 0.001). Regression analysis of Aß1-42/Aß1-40 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 Aß1-42 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 Aß1-42/Aß1-40 ratios with 85.3% sensitivity and 96.2% specificity. APOE 4 carriers had significantly higher Aß1-42/Aß1-40 ratios than the non-carriers (F = 4.839, p = 0.015). An independent group of case-control subjects validated both cut-off values for Aß1-42/Aß1-40 (100% sensitivity and 83.3% specificity) and for Aß1-42 (100% sensitivity and 75.3% specificity). In a subgroup of longitudinal follow- up study, we found that the plasma Aß was relatively stable with an interval of approximately 3 months. In conclusion, we found that the plasma Aß1-42 is a useful biomarker for AD. The Aß1-42/Aß1-40 ratio improves the diagnostic power of the plasma Aß biomarkers. The iron nanoparticles and IMR provides a novel method to measure plasma Aß and could serve as an important clinical tool for the diagnosis of neurodegenerative diseases.

Clinical presentations and skin denervation in amyloid neuropathy due to transthyretin Ala97Ser.

OBJECTIVE: Familial amyloid polyneuropathy (FAP) due to amyloidogenic transthyretin (TTR) is often associated with impairment of thermonociceptive functions. This study investigated skin innervation and its clinical significance in genetically defined FAP due to a hot-spot Ala97Ser TTR mutation (Ala97Ser). METHODS: Skin biopsies were performed on the distal leg of patients with Ala97Ser, and intraepidermal nerve fiber (IENF) densities were quantified. RESULTS: There were 19 unrelated patients with Ala97Ser manifesting a late-onset (59.47 +/- 5.70 years) generalized neuropathy with disabling motor, sensory, and autonomic symptoms. Against a background of a slowly progressive course, 7 patients (36.8%) exhibited additional rapid declines in neurologic deficits, which were associated with elevation of the protein content in the CSF (p < 0.001). The IENF density was markedly reduced in Ala97Ser patients compared to age- and gender-matched controls (0.99 +/- 1.11 vs 8.31 +/- 2.87 fibers/mm, p < 0.001). Skin denervation was present in all patients and was lower in patients with a higher disability grade (0.17 +/- 0.26 vs 1.37 +/- 1.16 fibers/mm, p = 0.003). Albuminocytologic dissociation in the CSF was observed in 14 patients (73.7%), and the IENF density was negatively correlated with the CSF protein concentration (p = 0.015). CONCLUSIONS: Skin denervation was common in Ala97Ser, and degeneration of cutaneous nerve terminals was correlated with the severity of clinical phenotypes and the level of CSF protein.

Asymmetric expression patterns of brain transthyretin in normal mice and a transgenic mouse model of Alzheimer's disease.

Brain asymmetry is linked with several neurological diseases, and transthyretin (TTR) is a protein sequestering beta-amyloid (Abeta) and helping to prevent the Alzheimer's disease (AD). We show, by real time reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization and Western blotting, that TTR exhibits a pattern of adult male-specific, leftward distribution in the mouse brain. This asymmetry appeared to be mainly due to the asymmetric distribution of the choroid plexus cells in the ventricles. Unlike the normal mice, however, the hemispheric levels of TTR transcripts of 2- and 6-month-old Tg2576 mice, a transgenic AD mouse model overexpressing Abeta, were symmetric in both sexes. Furthermore, at the age of 10 months when the pathological AD-like features had developed, the level of TTR transcripts in the left hemisphere of the male Tg2576 became significantly lower than the right one. This lowering of TTR transcript is accompanied with a higher Abeta level in the left hemisphere of the 10-month Tg2576 males. Finally, for both genders, the TTR transcript levels in the two hemispheres of aged Tg2576 mice were lower than either the adult Tg2576 or the aged nontransgenic controls. Based on the above, we suggest scenarios to correlate the changes in the levels and hemispheric patterns of TTR expression to the pathogenesis of AD.

DNA haplotype analysis of CAG repeat in Taiwanese Huntington's disease patients.

We studied the expanded CAG repeat and adjacent CCG repeat in 53 Huntington's disease (HD) patients and 172 unrelated normal subjects matched to the patients for ethnic origin. The range of the CAG repeat varied from 38 to 109 in the HD patients and from 10 to 29 in the control group. A significant negative correlation was found between the age at onset and the CAG expansion, with no significant influence of the adjacent CCG repeat on the age at onset by multiple regression analysis. Allelic association using CCG repeat and 2 flanking dinucleotide repeat markers within 150 kb of the HD gene revealed linkage disequilibrium for 2 of 3 markers. Haplotype analysis of 24 HD families using these markers identified 3 major haplotypes underlying 87.5% of HD chromosomes. The data suggested frequent haplotypes in the Taiwanese population on which one or more mutational events leading to the disease occurred.

Dimensions of affective semantic meaning--behavioral and evoked potential correlates in Chinese subjects.

The affective meaning of words can be quantified statistically by the 'semantic differential technique'. We studied a total of 55 Chinese adults in two experiments: first, 210 nouns were rated by 32 subjects. Factor analysis on these data yielded three independent semantic dimensions. Semantically unique words were used in electrophysiological experiments in another group of 23 healthy right-handed adults. Words of similar physical appearance belonging to different semantic classes were presented visually in random order. The electroencephalogram [corrected] was recorded in 32 channels. Evoked activity was computed for each semantic class. Significant differences in electrical brain activation between semantic word classes were seen as early as 80 ms after stimulus onset confirming related findings in German subjects. These results illustrate similar early neural activation in subject groups of different language and culture.

Tissue segmentation-assisted analysis of fMRI for human motor response: an approach combining artificial neural network and fuzzy C means.

The authors have developed an automated algorithm for segmentation of magnetic resonance images (MRI) of the human brain. They investigated the quantitative analysis of tissue-specific human motor response through an approach combining gradient echo functional MRI and automated segmentation analysis. Fifteen healthy volunteers, placed in a 1.5 T clinical MR imager, performed a self-paced finger opposition throughout the activation periods. T1-weighted images (WI), T2WI, and proton density WI were acquired for segmentation analysis. Single-slice axial T2* fast low-angle shot (FLASH) images were obtained during the functional study. Pixelwise cross-correlation analysis was performed to obtain an activation map. A cascaded algorithm, combining Kohonen feature maps and fuzzy C means, was applied for segmentation. After processing, masks for gray matter, white matter, small vessels, and large vessels were generated. Tissue-specific analysis showed a signal change rate of 4.53% in gray matter, 2.98% in white matter, 5.79% in small vessels, and 7.24% in large vessels. Different temporal patterns as well as different levels of activation were identified in the functional response from various types of tissue. High correlation exists between cortical gray matter and subcortical white matter (r = 0.957), while the vessel behaves somewhat different temporally. The cortical gray matter fits best to the assumed input function (r = 0.957) followed by subcortical white matter (r = 0.829) and vessels (r = 0.726). The automated algorithm of tissue-specific analysis thus can assist functional MRI studies with different modalities of response in different brain regions.

Dimethylacetamide, ethylenediamine, and diphenylmethane diisocyanate poisoning manifest as acute psychosis and pulmonary edema: treatment with hemoperfusion.

CASE REPORT: A 27-year-old man, employed by a synthetic fiber company, had been exposed to dimethylacetamide, ethylenediamine, and diphenylmethane diisocyanate in a confined space continuously for 4-6 hours per day for 3 days before admission. Hallucinations and delusions were noted at admission; pulmonary edema developed subsequently. The electroencephalogram showed diffuse moderate cortical dysfunction and slow waves at 4-7 Hz, 20-80 microV. Seizures, liver injury, and rhabdomyolysis were noted on the 4th hospital day. The patient was treated by hemoperfusion with a decrease in urine dimethylacetamide from 3,265 mg/g to 4 mg/g creatinine over 4 days. Serial urinary dimethylacetamide and electroencephalogram correlated with the clinical condition.

Secondary syphilis in persons infected with and not infected with HIV-1: a comparative immunohistologic study.

To better understand the cutaneous immune response to Treponema pallidum, we performed an immunohistologic study of skin biopsies from a total of 11 patients with secondary syphilis; biopsies from five persons infected with HIV-1 were included in the analysis to assess at the tissue level the impact of concomitant HIV-1 infection on disease expression. In all of the biopsies, staining for HLA-DR, a marker for cellular activation, was observed among infiltrating leukocytes, dermal vascular endothelial cells, and keratinocytes. Infiltrating mononuclear cells stained positively for CD4 or CD8, with CD4+ cells always being in the majority. Surprisingly, most of the CD4+ cells had histiocytic, rather than lymphocytic, morphologic characteristics. Immunostaining for CD14 confirmed that these cells were monocytic in origin, whereas immunostaining for CD3 revealed that the lymphocytes were predominantly CD8+ cytotoxic T cells. B cells were not detected despite the presence of variable numbers of plasma cells in all specimens. By immunofluorescence, all of the specimens demonstrated perivascular deposition of immunoglobulins, complement, or fibrinogen; linear staining at the dermal-epidermal junction also was observed in most of the specimens. No differences in immunocytochemical or immunofluorescence staining patterns were observed between the specimens from patients who were HIV positive and patients who were HIV negative. In addition to providing a more precise definition of the infiltrating cells in syphilitic lesions, our results, taken as a whole, indicate that cellular immune processes are largely responsible for the development of cutaneous manifestations during syphilitic infection and that coinfection with HIV-1 has little discernible effect on the cutaneous response to T. pallidum.

Model-free functional MRI analysis using Kohonen clustering neural network and fuzzy C-means.

Conventional model-based or statistical analysis methods for functional MRI (fMRI) suffer from the limitation of the assumed paradigm and biased results. Temporal clustering methods, such as fuzzy clustering, can eliminate these problems but are difficult to find activation occupying a small area, sensitive to noise and initial values, and computationally demanding. To overcome these adversities, a cascade clustering method combining a Kohonen clustering network and fuzzy, means is developed. Receiver operating characteristic (ROC) analysis is used to compare this method with correlation coefficient analysis and t test on a series of testing phantoms. Results shown that this method can efficiently and stably identify the actual functional response with typical signal change to noise ratio, from a small activation area occupying only 0.2% of head size, with phase delay, and from other noise sources such as head motion. With the ability of finding activities of small sizes stably this method can not only identify the functional responses and the active regions more precisely, but also discriminate responses from different signal sources, such as large venous vessels or different types of activation patterns in human studies involving motor cortex activation. Even when the experimental paradigm is unknown in a blind test such that model-based methods are inapplicable, this method can identify the activation patterns and regions correctly.

A comparison of three gastric lavage methods using the radionuclide gastric emptying study.

To determine the percentage of liquid gastric contents experimentally removable by available orogastric lavage systems, five healthy young volunteers were asked to ingest 1 mCi of liquid technicium-99m diethylenetriaminepentaacetic acid (Tc99m-DTPA) mixed with 50 ml tap water. Five minutes afterwards, the radionuclide was lavaged using one of three different techniques-a single syringe method, a closed gravity drainage system, and a closed double syringe method--while continuous radioisotope camera images were taken. Control images, with no lavage performed, were also taken. All of the orogastric lavage methods removed a mean of between 80% and 85% of the stomach contents. The double syringe method was the quickest, while the single syringe method was least tolerated. When compared with control, none of the lavage techniques pushed gastric contents into the duodenum. Thus, in terms of amount of liquid gastric contents removed, there was no one method that removed more than the others. Caution should be exercised in assuming that 80-85% of a liquid gastric ingestion can be removed by lavage in the uncontrolled clinical setting. The use of any orogastric lavage for ingestion evacuation should be undertaken knowing that it is a morbid procedure and usually not necessary.

Functional MRI of the activated human visual cortex.

We explored the possibility of performing functional magnetic resonance imaging of visual evoked response in the primary visual cortex with a clinical MRI imager of 1.5 tesla. Gradient echo pulse sequence was chosen to acquire the functional image and binocular flash visual stimulation by light-proof goggles containing light emitting diodes was used as the source of cerebral activation. Data processing was performed utilizing direct subtraction for averaged images, correlation coefficient, statistical parametric mapping and matched filter. Of those methods, correlation coefficient and statistic parametric mapping proved to be the methods of choice in our study.

Clinical correlates of quantitative acoustic analysis in ataxic dysarthria.

The speech of 15 Taiwanese patients with cerebellar dysfunction and ataxic dysarthria was investigated utilizing techniques of acoustic analysis and instrumental measurement. Semiquantitative assessment of cerebellar function (SQACF) was also performed. The results of the acoustic analysis of the cerebellar speech were then correlated with the findings in the SQACF. The overlapping of voice onset time highly correlates with truncal ataxia as well as eye movement abnormality and eye-hand coordination. The prolongation of vowel duration also correlates significantly with tandem walking, dysdiadochokinesia and eye movement abnormality. The correlation of the speech function with other cerebellar motor functions provides further insight into the functional anatomy for cerebellar speech motor control. This study concludes that the midline structures-vermis and fastigial nucleus-seem to be the primary focus for the coordination of motor speech in the cerebellum.

Treatment of acute gouty arthritis with intramuscular ketorolac tromethamine.

Nine consecutive patients presenting with acute gouty arthritis were treated with ketorolac 60 mg intramuscularly (IM). The average age was 58. Seven were male, and six were black. Pain was quantified in 6 of the patients using a 10-cm visual analog scale that the patients completed before and 30, 60, and 90 minutes after ketorolac administration. The mean pain score (+/- standard error of the mean) dropped from 6.43 (+/- 1.25), out of a possible 10, to 1.01 (+/- 35) (P < .01). There were no side effects of the medication. All of the patients were able to leave the treatment area satisfied with their treatment. None of the patients required crutches at discharge.

Autonomic activities in hyperhidrosis patients before, during, and after endoscopic laser sympathectomy.

Three hundred palmar hyperhidrosis (PH) patients have been treated with video endoscopic laser sympathectomy during the last 2 years. Monitoring the palmar skin perfusion (PSP) and palmar skin temperature (PST) has been used intraoperatively to aid the confirmation of the correct sympathetic segment for laser ablation. The preoperative and postoperative PSP and PST and sympathetic skin response (SSR) also have been measured to evaluate the therapeutic effect of this method. An apparent increase of PSP would occur intraoperatively after the interruption of the T2 sympathetic segment, and then a gradual elevation of PST would follow after the extirpation of the segment. A rise of PST of about 3 degrees C after laser ablation of the appropriate segment indicated sufficient denervation of the hand and predicted long-lasting relief of PH. Furthermore, both PSP and PST also significantly increased after the operation. The postoperative elevation of the PST (usually about 3 degrees C) is similar to that recorded during intraoperative monitoring. The amplitude and the latency of SSR in the palm and sole were recorded both before and after sympathectomy. A remarkable decrease of palmar SSR amplitude and its ratio was found postoperatively by comparing it with that of plantar SSR in the same patient. These autonomic activity changes have correlated well with the postoperative satisfaction of the patients. Based on our study, the anatomic identification confirmed by the sympathetic monitorings has proved essential to achieve a definite and adequate sympathectomy leading to a satisfactory resolution of PH without the need of a tissue diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)