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The general theoretical-experimental method recently formulated for investigating dynamic properties of slow-orientational anisotropic ESR hyperfine centers under orientational diffusion is applied to normal nitroxide radicals with14N(I=1). This application permits the determination of slow-orientational correlation times, motional inhomogeneous linewidths, and temperature-dependent hyperfine coupling constants from the first- and second-derivative peak positions of nitroxide ESR hyperfine structures in polycrystalline-amorphous condensed matter. [ABSTRACT FROM AUTHOR]

Abstract: This letter details the collective views of a number of independent researchers on the technical assessment and evaluation of environmental models and software. The purpose is to stimulate debate and initiate action that leads to an improved quality of model development and evaluation, so increasing the capacity for models to have positive outcomes from their use. As such, we emphasize the relationship between the model evaluation process and credibility with stakeholders (including funding agencies) with a view to ensure continued support for modelling efforts. Many journals, including EM&S, publish the results of environmental modelling studies and must judge the work and the submitted papers based solely on the material that the authors have chosen to present and on how they present it. There is considerable variation in how this is done with the consequent risk of considerable variation in the quality and usefulness of the resulting publication. Part of the problem is that the review process is reactive, responding to the submitted manuscript. In this letter, we attempt to be proactive and give guidelines for researchers, authors and reviewers as to what constitutes best practice in presenting environmental modelling results. This is a unique contribution to the organisation and practice of model-based research and the communication of its results that will benefit the entire environmental modelling community. For a start, our view is that the community of environmental modellers should have a common vision of minimum standards that an environmental model must meet. A common vision of what a good model should be is expressed in various guidelines on Good Modelling Practice. The guidelines prompt modellers to codify their practice and to be more rigorous in their model testing. Our statement within this letter deals with another aspect of the issue – it prompts professional journals to codify the peer-review process. Introducing a more formalized approach to peer-review may discourage reviewers from accepting invitations to review given the additional time and labour requirements. The burden of proving model credibility is thus shifted to the authors. Here we discuss how to reduce this burden by selecting realistic evaluation criteria and conclude by advocating the use of standardized evaluation tools as this is a key issue that needs to be tackled. [Copyright &y& Elsevier]

Ground penetrating radar studies of four representative active hack-barrier dunes, combined with radiocarbon and photon-stimulated-luminescence dating techniques and soils analysis, reveal phases of alternating dune activity and stabilization along the North Carolina-Virginia coast. Two smaller dunes represent only the current phase of dune activity. Two larger dunes preserve evidence of three phases of dune development lea. 740, 1260 and 1810 AD) and intervening phases of soil development. Climate, particularly moisture conditions, played a part in the timing of dune activity and stabilization events. All three dune phases are associated with drier conditions whereas soils formation is associated with humid conditions. Modern l phase 31 dunes are more widespread along the coast and their formation is attributed to a combination of dry conditions, increased storminess associated with the Little Ice Age, and rising sea level. Tidal inlet closing and storm overwash processes likely provided sediment point sources for individual dune masses. The longer history and much greater volume of dune sand in the area of the two larger dunes suggests a greater sediment supply in this locality. [ABSTRACT FROM AUTHOR]

In the article, the author wishes to look at two forms of philosophical argument or critique. The two forms of derived argument, and critiques, which the author wishes to use, will be called internal and external critique. Scholar Stephan Körner uses terms like 'exhibition analysis,' an explication of a concept, or theory, or system, or paradigm under review; and 'replacement analysis,' an explication demanding a replacement of a concept or system or major review, because of perceived inadequacies or inconsistencies.

Data collected with the depression scale (DEP) of the Brief Assessment Scale (BAS) at interviews with 811 elderly subjects were analysed to determine which of its 21 individual items could be selected to produce a short screening scale for depression which would have less than 10 items and a Cronbach's alpha above 0.8. Eight items which fulfilled these requirements were selected to form the Even Briefer Assessment Scale for Depression (EBAS DEP). The validity of the scale was assessed against psychiatric diagnoses made on a subset of 211 subjects. The EBAS DEP had a sensitivity and specificity for a diagnosis of a DSM-III-R mood disorder (depressed) of 0.91 and 0.72, respectively. The EBAS DEP could be useful as a brief screen for depression in busy hospital and primary care settings where a full assessment of mood for every patient is impractical. The EBAS DEP is presented, together with instructions for its use, to enable independent study of its reliability and validity in other populations. [ABSTRACT FROM AUTHOR]

Reliability studies for the Brief Assessment Schedule between raters trained in England, West Germany and Australia have been carried out, as this instrument is now being widely used for assessing psychiatric morbidity among elderly residents in care in several countries. Interrater reliability for the dementia and depression scales for raters from the different countries working in English was high. However, the interlingual (English-German) reliability for the dementia scale was less satisfactory. [ABSTRACT FROM AUTHOR]

The paramagnetic resonance powder spectrum of an electron or nuclear spin system involving an isotropic Zeeman and an axially symmetric, first-order fine-structure splitting has been numerically investigated for the purpose of finding a simple, direct, and accurate method for determining its single-crystal parameters in polycrystalline-amorphous samples. It is shown that from the positions and relative intensities of some selected first- and second-derivative peaks of the axial fine-structure powder spectrum, one can directly determine with high accuracy the associated coupling constant, single-crystal line shape, and single-crystal linewidth for the external magnetic field perpendicular as well as parallel to the axially symmetric axis. The results of an experimental application of this method to the case of a randomly oriented zinc chelate biradical system are presented. The new powder spectrum method is applicable to first-order axially symmetric ESR and NMR quadrupole and dipole-dipole pair centers with isotropic g values under rigid state or slow tumbling orientational motion in polycrystalline-amorphous substances. [ABSTRACT FROM AUTHOR]

The article discusses the London and South-East Region Alzheimer's Disease (LASER-AD) study of antipsychotics and cognitive decline of patients with Alzheimer's disease. LASER-AD study provides limited reassurance in relation to the occasional prescription of novel antipsychotics to elderly people with dementia. The merit of the LASER-AD study is in examining the potential negative consequences of novel antipsychotic use which have caused great concern among patients and physicians.

The effects of polynomial interpolation and internal standardization drift corrections on the inter-measurement dispersion (statistical) of isotope ratios measured with a multi-collector plasma mass spectrometer were investigated using the (analyte, internal standard) isotope systems of (Ni, Cu), (Cu, Ni), (Zn, Cu), (Zn, Ga), (Sm, Eu), (Hf, Re) and (Pb, Tl). The performance of five different correction factors was compared using a (statistical) range based merit function ωm which measures the accuracy and inter-measurement range of the instrument calibration. The frequency distribution of optimal correction factors over two hundred data sets uniformly favored three particular correction factors while the remaining two correction factors accounted for a small but still significant contribution to the reduction of the inter-measurement dispersion. Application of the merit function is demonstrated using the detection of Cu and Ni isotopic fractionation in laboratory and geologic-scale chemical reactor systems. Solvent extraction (diphenylthiocarbazone (Cu, Pb) and dimethylglyoxime (Ni)) was used to either isotopically fractionate the metal during extraction using the method of competition or to isolate the Cu and Ni from the sample (sulfides and associated silicates). In the best case, differences in isotopic composition of ± 3 in the fifth significant figure could be routinely and reliably detected for Cu65/63 and Ni61/62. One of the internal standardization drift correction factors uses a least squares estimator to obtain a linear functional relationship between the measured analyte and internal standard isotope ratios. Graphical analysis demonstrates that the points on these graphs are defined by highly non-linear parametric curves and not two linearly correlated quantities which is the usual interpretation of these graphs. The success of this particular internal standardization correction factor was found in some cases to be due to a fortuitous, scale dependent, parametric curve effect. [ABSTRACT FROM AUTHOR]

Objective: Although the evidence base for the use of antipsychotics in older people with schizophrenia is generally of low quality, it tends to support the use of atypical antipsychotics. Only limited information regarding longer term adherence to these apparently more effective drugs is available. The aim of this study was to determine predictors of adherence to risperidone or olanzapine in patients over 60.Methods: Patients receiving care from old age psychiatrists for their schizophrenia were randomised to treatment with olanzapine or risperidone and were followed for up to 3(1/2) years. Kaplan-Meier curves were generated to assess the univariate effect of randomisation drug on long-term adherence and Cox regression adjusted for baseline variables which may have affected adherence.Results: In total, 60.6% of the 66 patients in the study were still taking their randomised drug by the end of the interval in which they remained under observation (64.7% olanzapine and 56.3% risperidone). This difference was non-significant. No baseline variable was associated with an increased risk of non-adherence, though the delivery form of pre-randomisation drug (oral or depot) was weakly (p = 0.054) associated with patients originally on depot being less likely to be adherent to an atypical drug.Conclusions: Overall adherence with atypical medication was good with almost two-thirds of the patients remaining on their randomisation drug for the interval in which they were under observation. Patients taken off depot were less likely to be adherent but there was no significant difference in adherence between olanzapine and risperidone. Scrutiny of the survival curves suggested that non-adherence is an early event in treatment and patients adherent at 6 months were likely to remain adherent over a longer time period. [ABSTRACT FROM AUTHOR]

Crop yield varies spatially and temporally due to several limiting factors, including soil type, nutrient availability water availability, weather, and crop varieties. It is difficult to quantify the severity of these limiting factors on crop yield as well as the spatial variation of crop yield before harvest. Remotely sensed aerial images can be used to improve estimates of mid-season crop yields. However, the success of such approaches is typically dependent on the image classification technique used. In this article, we develop an automated self-organizing map (SOM) neural image classification technique and evaluate it with respect to the widely used ISODATA clustering method using visual assessment of preservation of image texture. We also develop hybrid SOM-back-propagation neural network (BPNN) models to predict crop yield from the Oakes Irrigation Test Area (OITA) research sites at Oakes, North Dakota. We used the SOM image classification technique to classify the composite visible and near-infrared (NIR) band aerial images from several parts of the OITA research site. SOM cluster centroids from individual grid images were used as inputs to the BPNN yield prediction models created for the years 1997, 1998, 1999, 2000, and 2001. The models using individual red, green, and NIR band digital data provided average corn yield prediction accuracies of more than 80% for every year, except for the NIR model in 1998 (45%). Individual year models were validated with individual band training and testing datasets from the other four years. Models using the green band dataset provided better validation results. Average corn yield prediction accuracies ranged from 55% to a maximum of 96%. Average corn yield prediction accuracies of validated models using the red band and NIR band datasets ranged from 33% to a maximum of 94% and from 36% to a maximum of 95%, respectively. This article establishes the use of hybrid SOM-BPNN modeling techniques to predict corn yield from aerial images at mid-crop season. [ABSTRACT FROM AUTHOR]

Associate-recognition has received little attention as a potential clinical tool for detecting early Alzheimer's disease (AD). As an important preliminary stage to investigating the paradigm's diagnostic utility, we designed and administered a verbal associate-recognition task to healthy elderly participants (n = 62) and compared their performance to that on traditional cued-recall PAL. In both test conditions, the stimulus list comprised of a mixture of highly imageable and less imageable word pairs. Overall, performance on the associate-recognition task was superior to that on the cued-recall analogue. This 'recognition advantage' was not attributable to the higher baseline or chance guessing rate in the associate-recognition condition, as the size of the recognition advantage varied across learning trials and stimulus imageability. In comparison to performance on the imageable stimuli, performance on the less imageable stimuli was poor in both associate-recognition and cued-recall conditions. Across the delay, performances were more likely to drop in the cued-recall condition than the associate-recognition condition. These results suggest that verbal associate-recognition may be clinically efficacious and better tolerated in elderly populations than traditional cued-recall paradigms. Although these results are encouraging, further research is required to examine the utility of associate-recognition in clinical populations, particularly early AD. [ABSTRACT FROM AUTHOR]

Abstract Rationale: Several lines of evidence suggest that nicotinic acetylcholine receptors (nAchRs) are involved in speed of information processing, and inspection time appears to be particularly sensitive to nicotinic manipulation. Objective: The present study sought to examine the effects of the nAchR antagonist mecamylamine on inspection time. Furthermore, the extent to which the anticholinesterase donepezil would reverse the effects of mecamylamine on inspection time was also examined. Methods: A double-blind, repeated measures design was employed. Subjects (n=6) received placebo, mecamylamine (20 mg PO) or mecamylamine (20 mg PO) and donepezil (5 mg PO). Inspection time and physiological measures were then assessed. Results: The mecamylamine condition and the mecamylamine and donepezil condition were associated with an increase in heart rate, when compared to the placebo condition. There was a significant slowing of inspection time in the mecamylamine condition, compared to placebo, which was partly reversed by donepezil. Conclusions: The slowing of inspection time following mecamylamine is consistent with the role of nAchRs in speed of information processing, and add to the evidence that IT may in part index nAchR system integrity. [ABSTRACT FROM AUTHOR]

We used a sub-sample from the Older Australian Twins Study to estimate the heritability of performance on three tests of language ability: Boston Naming Test (BNT), Letter/Phonemic Fluency (FAS) and Category/Semantic Fluency (CFT) Tests. After adjusting for age, sex, education, mood, and global cognition (GC), heritability estimates obtained for the three tests were 0.35, 0.59, and 0.20, respectively. Multivariate analyses showed that the genetic correlation were high for BNT and CFT (0.61), but low for BNT and FAS (0.17), and for FAS and CFT (0.28). Genetic modelling with Cholesky decomposition indicated that the covariation between the three measures could be explained by a common genetic factor. Environmental correlations between the language ability measures were low, and there were considerable specific environmental influences for each measure. Future longitudinal studies with language performance and neuroimaging data can further our understanding of genetic and environmental factors involved in the process of cognitive aging. [ABSTRACT FROM AUTHOR]

Accumulation of β-amyloid (Aβ) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (ɛ4 carrier[ɛ4+], ɛ4 non-carrier[ɛ4−]) and brain-derived neurotrophic factor (BDNFVal/Val, BDNFMet) in the extent to which they moderate Aβ-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aβ neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aβ positron emission tomography neuroimaging was used to classify participants as Aβ− or Aβ+. Relative to Aβ−ɛ4−, Aβ+ɛ4+ individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40-1.22), while Aβ+ɛ4− individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aβ−ɛ4− and Aβ−ɛ4+ groups. Among Aβ+ individuals, ɛ4+/BDNFMet participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ɛ4−/BDNFVal/Val participants (d=0.90-1.02). At least two genetic loci affect the rate of Aβ-related cognitive decline. Aβ+ɛ4+/BDNFMet individuals can expect to show clinically significant memory impairment after 3 years, whereas Aβ+ɛ4+/BDNFVal/Val individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aβ− and Aβ+ ɛ4− groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials. [ABSTRACT FROM AUTHOR]

The aim of this paper was to investigate the association of three well-recognised dietary patterns with cognitive change over a 3-year period. Five hundred and twenty-seven healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing completed the Cancer Council of Victoria food frequency questionnaire at baseline and underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months follow-up. Individual neuropsychological test scores were used to construct composite scores for six cognitive domains and a global cognitive score. Based on self-reported consumption, scores for three dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western diet and (3) prudent diet were generated for each individual. Linear mixed model analyses were conducted to examine the relationship between diet scores and cognitive change in each cognitive domain and for the global score. Higher baseline adherence to the AusMeDi was associated with better performance in the executive function cognitive domain after 36 months in apolipoprotein E (APOE) ɛ4 allele carriers (P<0.01). Higher baseline western diet adherence was associated with greater cognitive decline after 36 months in the visuospatial cognitive domain in APOE ɛ4 allele non-carriers (P<0.01). All other results were not significant. Our findings in this well-characterised Australian cohort indicate that adherence to a healthy diet is important to reduce risk for cognitive decline, with the converse being true for the western diet. Executive function and visuospatial functioning appear to be particularly susceptible to the influence of diet. [ABSTRACT FROM AUTHOR]

Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ɛ4 and site). In AD, plasma iron, transferrin, transferrin saturation and red cell folate levels exhibited a significant distortion of their customary relationship to hemoglobin levels. There was a strong association between anemia and AD (adjusted odds ratio (OR)=2.43, confidence interval (CI) (1.31, 4.54)). Moreover, AD emerged as a strong risk factor for anemia on step-down regression, even when controlling for all other available explanations for anemia (adjusted OR=3.41, 95% CI (1.68, 6.92)). These data indicated that AD is complicated by anemia, which may itself contribute to cognitive decline. [ABSTRACT FROM AUTHOR]

Dementia is a global epidemic with Alzheimer's disease (AD) being the leading cause. Early identification of patients at risk of developing AD is now becoming an international priority. Neocortical Aβ (extracellular β-amyloid) burden (NAB), as assessed by positron emission tomography (PET), represents one such marker for early identification. These scans are expensive and are not widely available, thus, there is a need for cheaper and more widely accessible alternatives. Addressing this need, a blood biomarker-based signature having efficacy for the prediction of NAB and which can be easily adapted for population screening is described. Blood data (176 analytes measured in plasma) and Pittsburgh Compound B (PiB)-PET measurements from 273 participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were utilised. Univariate analysis was conducted to assess the difference of plasma measures between high and low NAB groups, and cross-validated machine-learning models were generated for predicting NAB. These models were applied to 817 non-imaged AIBL subjects and 82 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) for validation. Five analytes showed significant difference between subjects with high compared to low NAB. A machine-learning model (based on nine markers) achieved sensitivity and specificity of 80 and 82%, respectively, for predicting NAB. Validation using the ADNI cohort yielded similar results (sensitivity 79% and specificity 76%). These results show that a panel of blood-based biomarkers is able to accurately predict NAB, supporting the hypothesis for a relationship between a blood-based signature and Aβ accumulation, therefore, providing a platform for developing a population-based screen. [ABSTRACT FROM AUTHOR]

Testosterone and gonadotropins have been associated with cognitive decline in men and the modulation of β amyloid (Aβ) metabolism. The relatively few studies that have investigated whether changes in one or a combination of these hormones influence Aβ levels have focused primarily on plasma Aβ1-40 and not on the more pathogenic Aβ1-42. Currently, no study has investigated whether these hormones are associated with an increase in brain amyloid deposition, ante mortem. Through the highly characterised Australian imaging, biomarkers and lifestyle study, we have determined the impact of these hormones on plasma Aβ levels and brain amyloid burden (Pittsburgh compound B (PiB) retention). Spearman's rank correlation and linear regression analysis was carried out across the cohort and within subclassifications. Luteinizing hormone (LH) was the only variable shown, in the total cohort, to have a significant impact on plasma Aβ1-40 and Aβ1-42 levels (beta=0.163, P<0.001; beta=0.446, P<0.001). This held in subjective memory complainers (SMC) (Aβ1-40; beta=0.208, P=0.017; Aβ1-42; beta=0.215, P=0.017) but was absent in mild cognitive impairment (MCI) and Alzheimer's disease (AD) groups. In SMC, increased frequency of the APOE-ɛ4 allele (beta=0.536, P<0.001) and increasing serum LH levels (beta=0.421, P=0.004) had a significant impact on PiB retention. Whereas in MCI, PiB retention was associated with increased APOE-ɛ4 allele copy number (beta=0.674, P<0.001) and decreasing calculated free testosterone (beta=−0.303, P=0.043). These findings suggest a potential progressive involvement of LH and testosterone in the early preclinical stages of AD. Furthermore, these hormones should be considered while attempting to predict AD at these earliest stages of the disease. [ABSTRACT FROM AUTHOR]

Previous studies suggest physical activity improves cognition and lowers Alzheimer's disease (AD) risk. However, key AD pathogenic factors that are thought to be influenced by physical activity, particularly plasma amyloid-β (Aβ) and Aβ brain load, have yet to be thoroughly investigated. The objective of this study was to determine if plasma Aβ and amyloid brain deposition are associated with physical activity levels, and whether these associations differed between carriers and non-carriers of the apolipoprotein E (APOE) ɛ4 allele. Five-hundred and forty six cognitively intact participants (aged 60-95 years) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) were included in these analyses. Habitual physical activity levels were measured using the International Physical Activity Questionnaire (IPAQ). Serum insulin, glucose, cholesterol and plasma Aβ levels were measured in fasting blood samples. A subgroup (n=116) underwent 11C-Pittsburgh compound B (PiB) positron emission tomography (PET) scanning to quantify brain amyloid load. Higher levels of physical activity were associated with higher high density lipoprotein (HDL) (P=0.037), and lower insulin (P<0.001), triglycerides (P=0.019) and Aβ1−42/1−40 ratio (P=0.001). After stratification of the cohort based on APOE ɛ4 allele carriage, it was evident that only non-carriers received the benefit of reduced plasma Aβ from physical activity. Conversely, lower levels of PiB SUVR (standardised uptake value ratio) were observed in higher exercising APOE ɛ4 carriers. Lower plasma Aβ1−42/1−40 and brain amyloid was observed in those reporting higher levels of physical activity, consistent with the hypothesis that physical activity may be involved in the modulation of pathogenic changes associated with AD. [ABSTRACT FROM AUTHOR]

High levels of amyloid-β (Aβ) have been associated with greater rates of decline in episodic memory over 18 months in healthy older adults. Serial assessments over shorter time intervals may facilitate earlier detection of Aβ-related memory decline in healthy older adults. In forty-four healthy older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Rate of Change Sub-Study, we compared rates of change in cognition over six months in healthy older adults with high and low levels of Aβ. High Aβ was associated with greater decline in episodic memory measures over 6 months in healthy older adults. [ABSTRACT FROM AUTHOR]

Background: Several studies have reported that peripheral levels of copper and ceruloplasmin (CP) can differentiate patients with Alzheimer's disease (AD) from non-AD cases. The aim of this study was to determine the diagnostic value of serum copper, CP, and non-CP copper levels in a large cohort of AD subjects. Methods: Serum copper and CP concentrations were measured at baseline and at 18-months in participants from the Australian Imaging Biomarkers and Lifestyle Study of Ageing. Cross-sectional and longitudinal analyses were conducted using both univariate and multivariate testing adjusting for age, gender, total protein, and ApoE ε4 genotype status. Results: There was no significant difference in levels of serum copper or CP between the AD and healthy control groups, however, we identified a near-significant decrease in non-CP copper in the mild cognitive impairment and AD groups at baseline (p = 0.02) that was significant at 18-months (p = 0.003). Conclusion: Our results suggest that there may be decreased non-CP copper levels in mild cognitive impairment and AD, which is consistent with diminished copper-dependent biochemical activities described in AD. [ABSTRACT FROM AUTHOR]

We aimed to characterize the nature and magnitude of cognitive decline in a group of adults with amnestic mild cognitive impairment (aMCI) with high and low levels of amyloid-β (Aβ) in relation to healthy older adults with low Aβ levels. Healthy older adults and adults with aMCI enrolled in the Australian Imaging, Biomarker, and Lifestyle study, completed the CogState brief battery at baseline and 18 months, and underwent positron emission tomography neuroimaging for Aβ at baseline. In this study, we included adults with MCI who had been classified as having high and low levels of Aβ and healthy older adults who had been classified as having low levels of Aβ. Linear model analyses adjusted for baseline cognitive function indicated that relative to healthy older adults with low Aβ, adults with aMCI and high Aβ showed greater decline in working memory and in verbal and visual episodic memory at 18 months. Adults with aMCI and low Aβ also showed greater decline in working memory; however they did not evidence any decline in episodic memory at 18 months. The results of our study suggests that relative to healthy older adults and adults with aMCI with low Aβ, adults with aMCI and high levels of Aβ showed faster rates of decline on measures of episodic memory over 18 months, and this was approximately twice that observed previously for healthy older adults with high Aβ levels. [ABSTRACT FROM AUTHOR]

Amyloid-β deposition in Alzheimer's disease is thought to start while individuals are still cognitively unimpaired and it is hypothesized that after an early phase of fast accumulation, a plateau is reached by the time of cognitive decline. However, few longitudinal Pittsburgh compound B-positron emission tomography studies have tested this hypothesis, and with conflicting results. The purpose of this work is to further our understanding of the dynamics of amyloid-β deposition in a large longitudinal cohort. A total of 32 patients with Alzheimer's disease, 49 subjects with mild cognitive impairment and 103 healthy controls underwent two Pittsburgh compound B-positron emission tomography scans 18 months apart. For each participant, a parametric map of Pittsburgh compound B-positron emission tomography rate of change was created [(follow-up scan - baseline scan)/follow-up duration] and entered in a voxelwise three-way analysis of covariance, with clinical status (healthy controls, mild cognitive impairment or Alzheimer's disease), disease progression (clinical conversion from healthy controls to mild cognitive impairment or Alzheimer's disease, or from mild cognitive impairment to Alzheimer's disease) and Pittsburgh compound B status (positive versus negative) as independent factors. Only a significant effect of the Pittsburgh compound B status was found: both Pittsburgh compound B-positive and -negative subjects showed a significant increase in amyloid-β deposition, with this increase being significantly higher in Pittsburgh compound B-positive individuals. This finding suggests either that Pittsburgh compound B-negative individuals have slower rates of amyloid-β accumulation than positive, or that the proportion of individuals showing significant increase in amyloid-β deposition, termed 'Pittsburgh compound B accumulators', is higher within the Pittsburgh compound B-positive group than within the Pittsburgh compound B-negative group. The bimodal distribution of the individual rates of neocortical amyloid-β accumulation observed support the existence of 'Pittsburgh compound B non-accumulators' and 'Pittsburgh compound B accumulators' and different clustering analyses led to a consistent threshold to separate these two subgroups (0.014-0.022 standardized uptake value ratio(pons)/year). The voxelwise three-way analysis of covariance was thus recomputed with the 'Pittsburgh compound B accumulators' only and the results were almost unchanged, with the Pittsburgh compound B-positive group showing higher accumulation than the Pittsburgh compound B-negative group. Finally, a significant negative correlation was found between Pittsburgh compound B rate of change and Pittsburgh compound B baseline burden, but only in the Pittsburgh compound B-positive group (r= -0.24; P=0.025). Higher rates of amyloid-β deposition are associated with higher amyloid-β burden suggesting that amyloid-β deposition does not reach a plateau when cognitive impairments manifest but is instead an ongoing process present even at the Alzheimer's disease stage. amyloid-β accumulation also seems to slow down at the latest stages of the process, i.e. in participants with the highest amyloid burden. Furthermore, this study identified the existence of Pittsburgh compound 'accumulators' and 'non-accumulators', notably within the Pittsburgh compound B-negative group, which may be a relevant concept for future studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: The prevalence of preexisting cognitive impairment (PreCI) is documented before cardiac surgery, but there is less information before noncardiac surgery. In addition, the prevalence of mild cognitive impairment, defined by different cognitive criteria and subjective complaints, and which may progress to Alzheimer disease, is unknown in these subjects. Because anesthesia and surgery have been implicated in Alzheimer disease pathology, we prospectively measured PreCI and mild cognitive impairment in subjects scheduled for total hip joint replacement surgery in an observational study. METHODS: One hundred fifty-two subjects 60 y of age and older who were scheduled for total hip joint replacement surgery underwent assessment, including neuropsychologic testing, 1 week before surgery. Test results were compared with published norms. PreCI was defined as impairment in two or more of seven cognitive tests, for which impairment in an individual test was defined as >= 2 SD below norms for that test. Amnestic mild cognitive impairment (aMCI) was defined as impairment >=1.5 SD below norms for results of the immediate and/or delayed Auditory Verbal Learning Test plus a subjective complaint. RESULTS: Subjects performed worse compared with normative data on five of seven neuropsychologic tests. Thirty (20% [95% CI, 13-26%]) subjects were classified as having PreCI. Thirty-four (22% [95% CI, 16-29%]) were classified as having aMCI. Ten (7%) subjects were classified as having both PreCI and aMCI, representing 33% of the 30 subjects with PreCI. CONCLUSIONS: The prevalence of aMCI in subjects scheduled for total hip joint replacement surgery is similar to that in the general community. PreCI and aMCI tend to identify different subjects. Because aMCI is known to progress to Alzheimer disease, future studies that track cognition before and after anesthesia and surgery should document the presence or absence of aMCI so that the rate of conversion to Alzheimer disease after anesthesia and surgery can be compared with the rate in the nonsurgical population. [ABSTRACT FROM AUTHOR]

Objectives: To explore the perceptions of family carers, older people and health professionals in Australia about what constitutes elder abuse. Methods: The Caregiving Scenario Questionnaire (CSQ) was disseminated to health professionals from two metropolitan hospitals, older volunteers and carers of older people with dementia recruited for other studies. Results: One hundred and twenty health professionals, 361 older people and 89 carers returned the surveys. x2 analyses indicated that significantly more health professionals than older people identified locking someone in the house alone all day (x2 (2)= 10.20, p = 0.006, Cramer’s V = 0.14), restraining someone in a chair (x2 (2) = 19.984, p = 0.0005, Cramer’s V = 0.19) and hiding medication in food (x2 (2) = 8.72, p = 0.013, Cramer’s V = 0.13) as abusive. There were no significant differences between healthy volunteer older people and carers in their perceptions of elder abuse. A significant minority (40.8%) of health professionals and over 50% of carers did not identify locking the care recipient alone in the house all day as abusive. Conclusion: In Australia, there is limited consensus between older people, carers and health professionals regarding what constitutes elder abuse. Health professionals were more likely to identify abusive and potentially abusive strategies correctly than carers or healthy older people, but nonetheless between one quarter and two-fifths [correction made here after initial online publication] of health professionals did not identify the abusive strategies. [ABSTRACT FROM AUTHOR]

The relationship between β-amyloid deposition and memory deficits in early Alzheimer's disease is unresolved, as past studies show conflicting findings. The present study aims to determine the relative contribution of regional β-amyloid deposition, hippocampal atrophy and white matter integrity to episodic memory deficits in non-demented older individuals harbouring one of the characteristic hallmarks of Alzheimer's disease, i.e. with β-amyloid pathology. Understanding these relationships is critical for effective therapeutic development. Brain magnetic resonance imaging and [(11)C]Pittsburgh Compound B-positron emission tomography scans were obtained in 136 non-demented individuals aged over 60 years, including 93 healthy elderly and 43 patients with mild cognitive impairment. Voxel-based correlations were computed between a memory composite score and grey matter volume, white matter volume and β-amyloid deposition imaging datasets. Hierarchical linear regression analyses were then performed using values extracted in regions of most significant correlations to determine the relative contribution of each modality to memory deficits. All analyses were conducted pooling all groups together as well as within separate subgroups of cognitively normal elderly, patients with mild cognitive impairment and individuals with high versus low neocortical β-amyloid. Brain areas of highest correlation with episodic memory deficits were the hippocampi for grey matter volume, the perforant path for white matter volume and the temporal neocortex for β-amyloid deposition. When considering these three variables together, only hippocampal volume and temporal β-amyloid deposition provided independent contributions to memory deficits. In contrast to global β-amyloid deposition, temporal β-amyloid deposition was still related to memory independently from hippocampal atrophy within subgroups of cognitively normal elderly, patients with mild cognitive impairment or cases with high neocortical β-amyloid. In the pre-dementia stage of Alzheimer's disease, subtle episodic memory impairment is related to β-amyloid deposition, especially in the temporal neocortex, and independently from hippocampal atrophy, suggesting that both factors should be independently targeted in therapeutic trials aimed at reducing cognitive decline. [ABSTRACT FROM AUTHOR]

Objective: Assess Aβ deposition longitudinally and explore its relationship with cognition and disease progression.Methods: Clinical follow-up was obtained 20 ± 3 months after [¹¹C]Pittsburgh compound B (PiB)-positron emission tomography in 206 subjects: 35 with dementia of the Alzheimer type (DAT), 65 with mild cognitive impairment (MCI), and 106 age-matched healthy controls (HCs). A second PiB scan was obtained at follow-up in 185 subjects and a third scan after 3 years in 57.Results: At baseline, 97% of DAT, 69% of MCI, and 31% of HC subjects showed high PiB retention. At 20-month follow-up, small but significant increases in PiB standardized uptake value ratios were observed in the DAT and MCI groups, and in HCs with high PiB retention at baseline (5.7%, 2.1%, and 1.5%, respectively). Increases were associated with the number of apolipoprotein E ε4 alleles. There was a weak correlation between PiB increases and decline in cognition when all groups were combined. Progression to DAT occurred in 67% of MCI with high PiB versus 5% of those with low PiB, but 20% of the low PiB MCI subjects progressed to other dementias. Of the high PiB HCs, 16% developed MCI or DAT by 20 months and 25% by 3 years. One low PiB HC developed MCI.Interpretation: Aβ deposition increases slowly from cognitive normality to moderate severity DAT. Extensive Aβ deposition precedes cognitive impairment, and is associated with ApoE genotype and a higher risk of cognitive decline in HCs and progression from MCI to DAT over 1 to 2 years. However, cognitive decline is only weakly related to change in Aβ burden, suggesting that downstream factors have a more direct effect on symptom progression. [ABSTRACT FROM AUTHOR]

There is some debate regarding the differing levels of plasma homocysteine, vitamin B12 and serum folate between healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). As part of the Australian Imaging Biomarker Lifestyle (AIBL) study of aging cohort, consisting of 1,112 participants (768 HC, 133 MCI patients, and 211 AD patients), plasma homocysteine, vitamin B12, and serum and red cell folate were measured at baseline to investigate their levels, their inter-associations, and their relationships with cognition. The results of this cross-sectional study showed that homocysteine levels were increased in female AD patients compared to female HC subjects (+16%, p-value < 0.001), but not in males. Red cell folate, but not serum folate, was decreased in AD patients compared to HC (-10%, p-value = 0.004). Composite z-scores of short- and long-term episodic memory, total episodic memory, and global cognition all showed significant negative correlations with homocysteine, in all clinical categories. Increasing red cell folate had a U-shaped association with homocysteine, so that high red cell folate levels were associated with worse long-term episodic memory, total episodic memory, and global cognition. These findings underscore the association of plasma homocysteine with cognitive deterioration, although not unique to AD, and identified an unexpected abnormality of red cell folate. [ABSTRACT FROM AUTHOR]

Objective: Although the evidence base for the use of antipsychotics in older people with schizophrenia is generally of low quality, it tends to support the use of atypical antipsychotics. Only limited information regarding longer term adherence to these apparently more effective drugs is available. The aim of this study was to determine predictors of adherence to risperidone or olanzapine in patients over 60. Methods: Patients receiving care from old age psychiatrists for their schizophrenia were randomised to treatment with olanzapine or risperidone and were followed for up to SV2 years. Kaplan—Meier curves were generated to assess the univariate effect of randomisation drug on long-term adherence and Cox regression adjusted for baseline variables which may have affected adherence. Results: In total, 60.6% of the 66 patients in the study were still taking their randomised drug by the end of the interval in which they remained under observation (64.7% olanzapine and 56.3% risperidone). This difference was non-significant. No baseline variable was associated with an increased risk of non- adherence, though the delivery form of pre-randomisation drug (oral or depot) was weakly (p — 0.054) associated with patients originally on depot being less likely to be adherent to an atypical drug. Conclusions: Overall adherence with atypical medication was good with almost two-thirds of the patients remaining on their randomisation drug for the interval in which they were under observation. Patients taken off depot were less likely to be adherent but there was no significant difference in adherence between olanzapine and risperidone. Scrutiny of the survival curves suggested that non-adherence is an early event in treatment and patients adherent at 6 months were likely to remain adherent over a longer time period. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: Elucidating the role of aggregated beta-amyloid in relation to gray matter atrophy is crucial to the understanding of the pathological mechanisms of Alzheimer disease and for the development of therapeutic trials. The present study aims to assess this relationship.Methods: Brain magnetic resonance imaging and [(11)C]Pittsburgh compound B (PiB)-positron emission tomography scans were obtained from 94 healthy elderly subjects (49 with subjective cognitive impairment), 34 patients with mild cognitive impairment, and 35 patients with Alzheimer disease. The correlations between global and regional neocortical PiB retention and atrophy were analyzed in each clinical group.Results: Global and regional atrophy were strongly related to beta-amyloid load in participants with subjective cognitive impairment but not in patients with mild cognitive impairment or Alzheimer disease. Global neocortical beta-amyloid deposition correlated to atrophy in a large brain network including the hippocampus, medial frontal and parietal areas, and lateral temporoparietal cortex, whereas regional beta-amyloid load was related to local atrophy in the areas of highest beta-amyloid load only, that is, medial orbitofrontal and anterior and posterior cingulate/precuneus areas.Interpretation: There is a strong relationship between beta-amyloid deposition and atrophy very early in the disease process. As the disease progresses to mild cognitive impairment and Alzheimer disease clinical stages, pathological events other than, and probably downstream from, aggregated beta-amyloid deposition might be responsible for the ongoing atrophic process. These findings suggest that antiamyloid therapy should be administered very early in the disease evolution to minimize synaptic and neuronal loss. [ABSTRACT FROM AUTHOR]

Background: South Asians comprise the largest ethnic minority population in the UK. This subgroup is known to have an elevated risk of stroke. However, there is limited data on patterns of cerebrovascular disease and associated risk factors in this population. [ABSTRACT FROM PUBLISHER]

Currently, the ‘amyloid hypothesis’ is the most widely accepted explanation for the pathogenesis of Alzheimer's disease (AD). According to this hypothesis, altered metabolism of the amyloid-β (Aβ) peptide is central to the pathological cascade involved in the pathogenesis of AD. Although Aβ is produced by almost every cell in the body, a physiological function for the peptide has not been determined, and the pathways by which Aβ leads to cognitive dysfunction and cell death are unclear. Numerous therapeutic approaches that target the production, toxicity and removal of Aβ are being developed worldwide. Although therapeutic treatment for AD may be imminent, the value and effectiveness of such treatment are largely dependent on early diagnosis of the disease. This review summarizes current knowledge of Aβ clearance, transport and degradation, and evaluates the use of such information in the development of diagnostic tools. The conflicting results of plasma Aβ ELISAs are discussed, as are the more promising results of Aβ imaging by positron emission tomography. Current knowledge of Aβ-binding proteins and Aβ-degrading enzymes is analysed in the context of a potential therapy for AD. Transport across the blood–brain barrier by the receptor for advanced glycation end products and efflux via the multi-ligand lipoprotein receptor LRP-1 is also reviewed. Enhancing clearance and degradation of Aβ remains an attractive therapeutic strategy, and improved understanding of Aβ clearance may lead to advances in diagnostics and interventions designed to prevent or delay the onset of AD.Molecular Psychiatry (2009) 14, 469–486; doi:10.1038/mp.2008.96; published online 16 September 2008 [ABSTRACT FROM AUTHOR]

Background Following an earlier study in which elderly patients with schizophrenia had their typical antipsychotic medication changed to olanzapine or risperidone, the 61 patients were followed for up to a further six months to see if either treatment was superior in terms of efficacy or side effects. Aims To determine whether either olanzapine or risperidone was superior in terms of efficacy or side effects when treating schizophrenia in late life. Methods Psychiatric symptoms, side effects and quality of life were rated every six weeks for 24 weeks of open label comparative treatment using standard measures. Group differences were examined using analysis of covariance and within-group changes over time were assessed using paired t-tests. Results There were 34 olanzapine and 32 risperidone patients who entered the study, but intention to treat data was only available for 61 of the 66 patients. There were no clinical or demographic differences between the groups. Parkinsonism, positive and negative symptoms of schizophrenia improved in both groups both from baseline switch to olanzapine or risperidone and during the six month follow-up after completion of crossover. No significant differences were seen between groups on most measures. However, patients treated with olanzapine showed a significantly greater improvement in quality of life from baseline compared to risperidone patients. Conclusions Both drugs were well tolerated and their use was associated with fewer symptoms of schizophrenia and less adverse effects than were seen when the patients were taking a typical antipsychotic at baseline. Olanzapine appears to have particular benefit with regard to quality of life. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To report 9 years' experience of an Australian memory clinic using the -Cambridge Mental Disorders in the Elderly Examination (CAMDEX) assessment schedule, summarizing patient demographics, diagnoses at presentation and the utility of four instruments used in distinguishing patients with and without dementia. METHODS: All patients seen at the clinic between December 1989 and September 1998 were assessed using the CAMDEX. Diagnoses were determined according to criteria of the International Classification of Diseases, tenth edition (ICD-10). RESULTS: The mean age of 577 patients seen was 72.9 years and 60.8% were female. Over 40% fulfilled ICD-10 diagnostic criteria for dementia in Alzheimer's disease. A further 24% had another dementing illness. Only 28 patients were 'normal'. There was no significant difference in the ability of the 107-item Cambridge cognitive examination, the 30-item mini-mental state examination, the 10-item abbreviated mental test score and the 26-item informant questionnaire on cognitive decline in the elderly to differentiate dementia patients from those who were normal or had functional psychiatric disorders. The four cognitive screening tools had high correlations with one another (r = - 0.57 to 0.93). CONCLUSION: Patient demographics and diagnoses were similar to those found in other clinics. Most people who attended the memory clinic had significant cognitive or psychiatric disorders. [ABSTRACT FROM AUTHOR]

BackgroundAtypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design. AimsTo demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone. MethodsElderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted. Results66 patients were randomised (mean age 69.6 [SD ± 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73–10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation—Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure. ConclusionsAfter switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Tetrahydroaminoacridine (THA), a centrally acting anticholinesterase, was used in a two-month, double-blind, placebo-controlled crossover trial to treat 10 patients meeting DSM-III-R criteria for dementia of the Alzheimer type. Eight patients continued to take THA for a further three months. Nausea was a frequent side-effect. Five patients developed abnormal liver function tests; liver biopsies showed evidence of liver cell necrosis in three patients, a granulomatous reaction in one, and one recovered after reduction of THA dosage. During the trial, patients as a group showed a significantly better performance on one of 10 memory tests when taking THA as compared to placebo. One patient showed a marked clinical improvement, six showed some improvement, and three patients showed no improvement with the active treatment. The group of eight patients who completed a further three months of THA treatment showed a significant deterioration on two psychological test scores. [ABSTRACT FROM AUTHOR]

This project aimed to determine overall psychosocial health (measured using the psychosocial dimension of the Functional Limitations Profile) and factors which influence this in a group of carers of those with dementia and to compare their psychosocial health with that of older people attending general practitioners (GPs); arthritis support groups and a pain clinic (out-patients) and a group of community dwellers undergoing renal dialysis. The carer group showed a significant decrease in recreation and pastimes and social interactions compared to older GP attenders. The carers showed similar restrictions in social interactions and recreation to those with chronic arthritis, but the latter were more impaired in the domains of emotional behaviour and sleep and rest. The older people attending a pain clinic did not differ in the areas of alertness and social interactions compared to the carer group. The dialysis group demonstrated the greatest dysfunction overall. These results suggest that the psychosocial health of carers of those with dementia is impaired, the profile of which differs from those suffering with chronic diseases. Social and recreation activities appear most affected in the carers. Commensurate with studies exploring the health status of those suffering from diseases, the measurement of the psychosocial health status of carers should also be considered in the scope of assessment and intervention. [ABSTRACT FROM AUTHOR]

This project aimed to determine overall psychosocial health (measured using the psychosocial dimension of the Functional Limitations Profile) and factors which influence this in a group of carers of those with dementia and to compare their psychosocial health with that of older people attending general practitioners (GPs); arthritis support groups and a pain clinic (out-patients) and a group of community dwellers undergoing renal dialysis. The carer group showed a significant decrease in recreation and pastimes and social interactions compared to older GP attenders. The carers showed similar restrictions in social interactions and recreation to those with chronic arthritis, but the latter were more impaired in the domains of emotional behaviour and sleep and rest. The older people attending a pain clinic did not differ in the areas of alertness and social interactions compared to the carer group. The dialysis group demonstrated the greatest dysfunction overall. These results suggest that the psychosocial health of carers of those with dementia is impaired, the profile of which differs from those suffering with chronic diseases. Social and recreation activities appear most affected in the carers. Commensurate with studies exploring the health status of those suffering from diseases, the measurement of the psychosocial health status of carers should also be considered in the scope of assessment and intervention. [ABSTRACT FROM AUTHOR]