Apolipoprotein E epsilon 4 allele is associated with increased atrophy in progressive mild cognitive impairment: a voxel-based morphometric study.

BACKGROUND: The apolipoprotein E (APOE) epsilon4 allele is a risk factor for Alzheimer's disease. Earlier studies have shown differences in brain structure according to the APOE epsilon4 status. OBJECTIVE: To assess possible differences in brain structure according to the APOE epsilon4 status in mild cognitive impairment (MCI) subjects in relation to conversion to dementia. METHODS: In a follow-up study of 56 MCI subjects, 13 MCI subjects progressed to dementia (PMCI) during a mean follow-up time of 31 months. Brain structure differences in both stable MCI (SMCI) and PMCI epsilon4 carriers and noncarriers in the baseline MRI scan were assessed with voxel-based morphometry. RESULTS: The SMCI epsilon4 carriers had atrophy in the amygdala and hippocampus compared to the SMCI noncarriers. The PMCI epsilon4 carriers revealed atrophy of the left inferior frontal gyrus and parietal cortex compared to the PMCI noncarriers. CONCLUSION: The rate of brain atrophy in certain brain areas may be increased in epsilon4-positive MCI subjects progressing to dementia.

Association of metabolic syndrome with Alzheimer disease: a population-based study.

OBJECTIVE: To assess the association of metabolic syndrome (MetS) with Alzheimer disease (AD). METHODS: The authors derived subjects from a population-based study of 980 randomly selected elderly subjects. After exclusion of all non-Alzheimer dementia cases, the final study population included 959 subjects (337 men and 622 women) aged 69 to 78 years. The presence of MetS was defined according to the National Cholesterol Education Program (Adult Treatment Panel III) criteria, and the diagnosis of AD was based on the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. RESULTS: Of the study subjects, 418 (43.6%) had MetS. Probable or possible AD was diagnosed in 45 subjects (4.7%). AD was more frequently detected in subjects with MetS than in subjects without MetS (7.2 vs 2.8%; p < 0.001). The prevalence of AD was higher in women with MetS vs women without the syndrome (8.3 vs 1.9%; p < 0.001), but in men with MetS, the prevalence of AD was not increased (3.8 vs 3.9%; p = 0.994). In univariate logistic regression analysis, MetS was significantly associated with AD (odds ratio [OR] 2.71; 95% CI 1.44 to 5.10). In multivariate logistic regression analysis including also apolipoprotein E4 phenotype, education, age, and total cholesterol, MetS was significantly associated with AD (OR 2.46; 95% CI 1.27 to 4.78). If only nondiabetic subjects were included in the multivariate analysis, MetS was still significantly associated with AD (OR 3.26; 95% CI 1.45 to 7.27). CONCLUSION: Metabolic syndrome is associated with Alzheimer disease in elderly subjects.

Chalcopyrite concentrate leaching with biologically produced ferric sulphate.

Biological ferric iron production was combined with ferric sulphate leaching of chalcopyrite concentrate and the effects of pH, Fe3+, temperature and solids concentration on the leaching were studied. The copper leaching rates were similar at pH of 1.0-1.8 and in the presence of 7-90 g L-1 Fe3+ despite massive iron precipitation with 90 g L-1 Fe3+. Increase of the leaching temperature from 50 degrees C to 86 degrees C and solids concentration from 1% to 10% increased the copper leaching rate. Increase in solids concentration from 1% to 10% decreased the copper yields from 80% to 40%. Stepwise addition of ferric iron did not improve the copper yields. CuFeS2, Ag and Cu1.96S potentials indicated the formation of a passivating layer, which consisted of jarosite and sulphur precipitates and which was responsible for the decreased leaching rates.

A voxel based morphometry study on mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer's disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. OBJECTIVE: To study the pattern of brain atrophy in MCI. METHODS: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p < 0.001. RESULTS: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere-for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. CONCLUSIONS: The MRI findings in MCI resemble those seen in early AD.

Optimization of metal sulphide precipitation in fluidized-bed treatment of acidic wastewater.

Sulphate-reducing biofilm and suspension processes were studied for treatment of synthetic wastewater containing sulphate, zinc and iron. With lactate supplemented wastewater with 170-230mg/l Zn and 58mg/l Fe, the following precipitation rates were obtained: 250 and 350mg/l d for Zn in fluidized-bed (FBR) and upflow anaerobic sludge blanket reactors, respectively, and 80mg/l d for Fe in both reactors with hydraulic retention time of 16h. The effluent Zn and Fe concentrations remained at less than 0.1 mg/l. The alkalinity produced in lactate oxidation increased the initial pH of 2.5-3, resulting in effluent pH of 7.5-8.5. The highest sulphate reduction rate was over 2000 mg/l d. In terms of sulphate reduction, hydrogen sulphide production and effluent alkalinity, the start-up of the FBR with the 10% fluidization rate was superior to the FBRs with 20-30% fluidization rates. With increased loading rates, high recycling rate became an advantage. After process failure caused by intentional overloading, the sulphate reduction partially recovered within 2 weeks. Metal precipitates in the reactors were predominantly FeS2, ZnS and FeS. The metal mass balance was as follows: 73-86% of Zn and Fe accumulated into the reactors and water level adjustors, 14-23% of the metals were washed out as precipitates and 0.05-0.15% remained as soluble metals. Biomass yield in the sulphate-reducing processes was 0.039-0.054g dry biomass (VS or VSS) per g of lactate oxidized or 0.035-0.074g dry biomass per g of sulphate reduced. The results of this work demonstrate that the lactate supplemented sulphate-reducing processes precipitated the metals as sulphides and neutralized the acidity of the synthetic wastewater.

Prevalence of mild cognitive impairment: a population-based study in elderly subjects.

OBJECTIVES: Mild cognitive impairment (MCI) has been suggested as a term for a boundary area between normal aging and dementia, especially Alzheimer's disease (AD). In follow-up studies, more than 50% of MCI subjects have been converted to dementia in 3-4 years. However, the epidemiology of MCI is not well known. This study was designed to determine the prevalence of MCI in an elderly population. METHODS: A total of 806 subjects (60-76 years of age) from a population-based random sample of 1150 subjects living in the city of Kuopio in eastern Finland were evaluated. Neuropsychological tests and a structured interview including the modified Clinical Dementia Rating (CDR) were used to apply the diagnostic criteria of MCI as proposed by Mayo Clinic Alzheimer's Disease Research Centre. Thus, subjects having a test score more than 1.5 SDs below the age appropriate mean in memory tests and a CDR score of 0.5 but no dementia, were diagnosed as having MCI. RESULTS: A total of 43 subjects, 5.3%, met the MCI criteria. MCI was more prevalent in older and less-educated subjects, but no difference was found between men and women. The CDR appeared to be the most important part of the criteria. The memory tests had less impact on prevalence variables. CONCLUSIONS: The low prevalence of MCI indicate that in a population-based study design its criteria may identify a more homogeneous group of subjects at the lower end of the cognitive continuum as contrasted with various other criteria of cognitive impairment in the elderly population. This is compatible with follow-up studies showing a high probability of dementia in the MCI group. Thus, probable candidates for trials of preventive intervention for dementia can be screened from the elderly population using these diagnostic criteria.

APOE-epsilon4 is associated with weight loss in women with AD: a population-based study.

OBJECTIVE: To investigate whether the APOE-epsilon4 allele is associated with weight loss in patients with AD or in nondemented elderly subjects. BACKGROUND: Weight loss has been considered a typical feature of AD. APOE-epsilon4 is a risk factor for AD and was recently proposed to be associated with weight loss in elderly women. It is not known whether APOE-epsilon4 is associated with weight loss in patients with AD or in the general population. METHODS: Weight and BMI measurements at an average interval of 3.5 years and APOE phenotype determination were performed in an elderly population (n = 980), including 46 patients with AD and 911 control subjects at the end of the follow-up. RESULTS: On average, patients with AD with the epsilon4 allele lost 1.9 +/- 4.0 kg (BMI 0.8 +/- 1.8 kg/m2) whereas epsilon4 noncarriers gained 1.2 +/- 3.8 kg (BMI 0.4 +/- 1.5 kg/m2) (both p < 0.05), after controlling for diabetes and exercise. However, when men and women were analyzed separately, weight loss was observed only in those women with AD with the epsilon4 allele. Clinically significant weight loss, defined as loss of > or = 5% of body weight, occurred more frequently in both patients with AD (30% versus 6%; p < 0.05) and control subjects (28% versus 18%; p < 0.001) carrying the epsilon4 allele. CONCLUSIONS: The APOE-epsilon4 allele may contribute to the unexplained weight loss in AD, especially in women.

Sensitisation to enzymes in the animal feed industry.

OBJECTIVES: To assess the prevalence of enzyme sensitisation in the animal feed industry. METHODS: A cross sectional study was conducted in four animal feed factories, where several enzymes had been used in powder form for 7-9 years. Before this study, enzymes in liquid form had started to be used. Sensitisation to enzymes was examined by skin prick and radioallergosorbent (RAST) tests. Altogether 218 workers were tested; 140 people in various tasks in manufacturing, where exposure to various organic dusts and to enzymes was possible, and 78 non-exposed office workers. The workers were interviewed for work related respiratory and skin symptoms. Total dust concentrations were measured by a gravimetric method. The concentrations of protease and alpha-amylase were measured with catalytic methods and that of xylanase with an immunological method. RESULTS: Ten workers (7%) were sensitised to enzymes in the exposed group of 140, whereas none were sensitised in the non-exposed group. Six of the sensitised people had respiratory symptoms at work: two of them especially in connection with exposure to enzymes. Enzyme concentrations in the air varied greatly: xylanase from less than 0.8 ng/m(3) up to 16 ng/m(3), alpha-amylase from less than 20 ng/m(3) up to 200 ng/m(3), and protease from less than 0.4 ng/m(3)up to 2900 ng/m(3). On average, highest xylanase and alpha-amylase concentrations were found in the various manufacturing sites, whereas the highest protease concentrations were found in areas of high total dust. CONCLUSIONS: Industrial enzymes may cause allergies in the animal feed industry. There is a need to assess exposure to enzymes at various phases of production, and to minimise exposures.

Associations between apolipoprotein E phenotype, glucose metabolism and cognitive function in men. An explorative study in a population sample.

AIMS: To investigate the associations of the apolipoprotein E phenotype (apoE) and disturbed glucose metabolism with cognitive function in a random population sample. METHODS: A cross-sectional study was conducted, in which 528 men aged 54 or 60 years were recruited randomly from a larger population-based sample of 1516 men. A subject was defined as having abnormal glucose tolerance (AGT), if he had a clinical diagnosis of diabetes, with either dietary or oral antidiabetic treatment or showed impaired glucose tolerance in an oral glucose tolerance test. The subjects were divided into three groups according to apolipoprotein E phenotypes: (a) E2/4, E3/4 or E4/4 (apoE E4); (b) E 3/3 (apoE E3); and (c) E2/2 or E2/3 (apoE E2). Memory function was examined using a word-list learning with Buschke's selective reminding method and test. Executive functions were assessed with the Trail Making Test A and B. RESULTS: Those subjects with apoE E2 and abnormal glucose metabolism demonstrated the worst cognitive executive control compared to other groups. Simple cognitive speed did not differ between the groups. CONCLUSIONS: The exploratory analyses revealed that subjects with apoE E2 allele and AGT had worse glycaemic control and cognitive executive control compared to other groups. Different apolipoprotein phenotypes together with impaired glucose tolerance may have different cumulative adverse effects on age-related cognitive performance. Some subgroups of subjects may be especially vulnerable to cognitive impairment.

Occupational IgE-mediated allergy to Tribolium confusum (confused flour beetle).

BACKGROUND: We report on IgE-mediated allergy in a worker caused by Tribolium confusum (confused flour beetle). These beetles lived in the "old" flour to which he was exposed in his work. CASE REPORT: A 35-year-old, nonatopic mechanic in a rye crispbread factory developed rhinitis, conjunctivitis, and asthmatic symptoms, as well as urticaria on his wrists, lower arms, hands, neck, and face, during the maintenance and repair of machines contaminated by flour. This flour had been in and on the machines for a long time, and it contained small beetles. The patient did not suffer any symptoms when handling fresh, clean flour. RESULTS: Skin prick tests with standard environmental allergens, storage mites, enzymes, flours, and molds were negative. A prick test with flour from the machines gave a 10-mm reaction. An open application of the same flour caused urticarial whealing on the exposed skin. Prick tests with fresh flour from the factory were negative. A prick test with minced T. confusum from the flour in the machines gave a 7-mm reaction. Histamine hydrochloride 10 mg/ml gave a 7-mm reaction. Specific serum IgE antibodies to T. confusum were elevated at 17.2 kU/l. Prick tests with the flour from the machines were negative in five control patients. CONCLUSIONS: The patient had occupational contact urticaria, rhinitis, conjunctivitis, and asthmatic symptoms from exposure to flour. His symptoms were caused by immediate allergy to the beetle T. confusum. Immediate allergy to this beetle has rarely been reported in connection with respiratory symptoms, but it may be more common. Contact urticaria from this source has not been reported before.

Cellulase allergy and challenge tests with cellulase using immunologic assessment.

OBJECTIVES: This study attempted to develop and evaluate a challenge test for diagnosing allergic asthma and rhinitis due to cellulase. METHODS: Challenge tests in a chamber were performed on 11 persons sensitized to cellulase. Four different enzyme-lactose mixtures, starting from a 0.03% mixture, were used. The enzyme dust was generated from a dry enzyme preparation mixed with lactose powder, using pressurized air. The cellulase concentration in the air was measured with an immunochemical method. RESULTS: Nasal, pharyngeal, or bronchial symptoms could be elicited at cellulase air concentrations of 1 to 1300 microg/m3. A dose-response relationship was observed for symptoms in repeated challenge tests with increasing concentrations of cellulase. For 2 persons skin symptoms could also be reproduced. CONCLUSION: The challenge method proved to be a practical means with which to simulate conditions at the worksite and elicit the specific respiratory symptoms of the patients.

Risk of enzyme allergy in the detergent industry.

OBJECTIVES: To assess the prevalence of enzyme sensitisation in the detergent industry. METHODS: A cross sectional study was conducted in a detergent factory. Sensitisation to enzymes was examined by skin prick and radioallergosorbent (RAST) tests. 76 Workers were tested; 40 in manufacturing, packing, and maintenance, and 36 non-exposed people in management and sales departments. The workers were interviewed for work related respiratory and skin symptoms. Total dust concentrations were measured by a gravimetric method, and the concentration of protease in air by a catalytic method. RESULTS: Nine workers (22%) were sensitised to enzymes in the exposed group of 40, whereas none were sensitised in the non-exposed group. All the sensitised people had symptoms at work; all had rhinitis and one had asthma. Protease concentrations were generally < 20 ng/m3, but occasional peak values up to 80 ng/m3 were detected in the packing and maintenance tasks, and high values of > 1 microgram/m3 in the mixing area. CONCLUSION: Despite the use of encapsulated enzyme preparations, high enzyme concentrations in workplace air are possible, resulting in a higher risk of sensitisation than expected.

Type-2 diabetes and cognitive function in a non-demented population.

OBJECTIVES: To study if type-2 (non-insulin-dependent) diabetes mellitus (NIDDM) is associated with cognitive dysfunction independently of clinically diagnosed dementia in an elderly population. MATERIAL AND METHODS: Cognitive function was investigated with a brief neuropsychological test battery in a non-demented elderly population consisting of 183 NIDDM (World Health Organization, 1985) patients and 732 non-diabetic subjects. RESULTS: Patients with NIDDM were impaired in the Trail-Making Test parts A and C, which may be a reflection of mildly affected frontal lobe/executive functions. Women with NIDDM performed better than non-diabetic subjects in the Mini-Mental State Examination. CONCLUSIONS: We conclude that NIDDM per se is not associated with impaired memory in the elderly, and the minor defects observed in tests of frontal lobe/executive functions are unlikely to affect daily living. In the non-demented population aged 69 78 years, NIDDM does not carry a significant risk of cognitive dysfunction, when compared to the non-diabetic subjects.

Guanfacine, but not clonidine, improves planning and working memory performance in humans.

The present study compares, using a double-blind, placebo controlled design the effects of two alpha 2-agonists, clonidine (0.5, 2, and 5 micrograms/kg) and guanfacine (7 and 29 micrograms/kg) on spatial working memory, planning and attentional set-shifting, functions thought to be dependent on the "central executive" of the prefrontal cortex. Blood pressure and the subjective feeling of sedation were affected equally by clonidine and guanfacine. The 0.5 microgram/kg and 5 micrograms/kg doses of clonidine disrupted spatial working memory, but the medium dose had no effect. The 0.5 and 2 micrograms/kg doses of clonidine increased impulsive responding in the planning test. The 5 micrograms/kg dose of clonidine slowed responding at effortful levels of planning and attentional set-shifting tests. The 29 micrograms/kg dose of guanfacine improved spatial working memory and planning. Guanfacine had no effect on attentional set-shifting. These data indicate that guanfacine improved planning and spatial working memory, but clonidine dose-dependently disrupted performance. It is possible that the greater selectivity of guanfacine for alpha 2A-adrenoceptor subtype may underlie its differences from clonidine.

Guanfacine and clonidine, alpha 2-agonists, improve paired associates learning, but not delayed matching to sample, in humans.

The present study compares the effects of two alpha 2-agonists, clonidine (0.5, 2, and 5 micrograms/kg, p.o.) and guanfacine (7 and 29 micrograms/kg, p.o.) in young healthy volunteers on their performance in visual paired associates learning (PAL) and delayed matching to sample (DMTS) visual short-term recognition memory tests. In the PAL test, clonidine 2 and guanfacine 29 micrograms/kg improved the subjects' performance. In the DMTS test, clonidine at 5 micrograms/kg delay-dependently impaired performance accuracy, and at 2 and 5 micrograms/kg it also slowed responses. Guanfacine had no effect on DMTS test performance. Clonidine 5 and guanfacine 29 micrograms/kg equally increased subjective feelings of sedation and reduced blood pressure. The results suggest that both clonidine and guanfacine facilitated PAL learning by improving "frontal strategies," but only clonidine disrupted "mneomonic processing" decreasing DMTS accuracy. The greater selectivity of guanfacine for alpha 2A-adrenoceptor subtype may explain the different profile of action of the drugs.

Glucose intolerance, cognitive impairment and Alzheimer's disease.

The literature on cognitive function and Alzheimer's disease in non-insulin-dependent diabetes, impaired glucose tolerance and hyperinsulinaemia are briefly summarized. Neuropsychological, epidemilogical and endocrine contributions are reviewed, with an emphasis on the insulin hypothesis as a potential pathophysiological mechanism for Alzheimer's disease.

Cognitive function in an elderly population with persistent impaired glucose tolerance.

OBJECTIVE: To study cognitive function in an elderly population with persistent impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Fasting and postload 2-h plasma glucose and insulin levels were determined at baseline in a population-based sample of 1,300 people and repeated an average of 3.5 years later in 980 subjects. At follow-up, cognitive function was evaluated in subjects with persistent normal glucose tolerance (NGT; n = 506) and IGT (n = 80) with a brief neuropsychological test battery. RESULTS: Subjects with persistent IGT scored lower in the Mini-Mental State Examination (MMSE) and in the Buschke Selective Reminding Test long-term memory scores. Multiple linear regression analysis revealed that age, education, and insulin levels (either fasting or 2-h value) were associated with the MMSE score in subjects with persistent IGT. Other potential risk factors for impaired cognitive function were not significantly associated with the MMSE score. CONCLUSIONS: Our study showed that persistent IGT in the elderly is associated with mildly impaired cognitive function, and hyperinsulinemia may account for this association.