Genetic and Environmental Influences on Language Ability in Older Adults: Findings from the Older Australian Twins Study.

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.

APOE and BDNF polymorphisms moderate amyloid ß-related cognitive decline in preclinical Alzheimer's disease.

Accumulation of ß-amyloid (Aß) 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 (BDNF(Val/Val), BDNF(Met)) in the extent to which they moderate Aß-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aß neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aß positron emission tomography neuroimaging was used to classify participants as Aß(-) or Aß(+). Relative to Aß(-)ɛ4(-), Aß(+)ɛ4(+) individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40-1.22), while Aß(+)ɛ4(-) individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aß(-)ɛ4(-) and Aß(-)ɛ4(+) groups. Among Aß(+) individuals, ɛ4(+)/BDNF(Met) participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ɛ4(-)/BDNF(Val/Val) participants (d=0.90-1.02). At least two genetic loci affect the rate of Aß-related cognitive decline. Aß(+)ɛ4(+)/BDNF(Met) individuals can expect to show clinically significant memory impairment after 3 years, whereas Aß(+)ɛ4(+)/BDNF(Val/Val) individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aß(-) and Aß(+) 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.

Dietary patterns and cognitive decline in an Australian study of ageing.

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.

Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

An anemia of Alzheimer's disease.

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.

Associations between gonadotropins, testosterone and ß amyloid in men at risk of Alzheimer's disease.

Testosterone and gonadotropins have been associated with cognitive decline in men and the modulation of ß amyloid (Aß) metabolism. The relatively few studies that have investigated whether changes in one or a combination of these hormones influence Aß levels have focused primarily on plasma Aß(1-40) and not on the more pathogenic Aß(1-42). 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 Aß 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 Aß(1-40) and Aß(1-42) levels (beta=0.163, P<0.001; beta=0.446, P<0.001). This held in subjective memory complainers (SMC) (Aß(1-40); beta=0.208, P=0.017; Aß(1-42); 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.

A blood-based predictor for neocortical Aß burden in Alzheimer's disease: results from the AIBL study.

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 Aß (extracellular ß-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 Aß accumulation, therefore, providing a platform for developing a population-based screen.

Physical activity and amyloid-ß plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing.

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-ß (Aß) and Aß brain load, have yet to be thoroughly investigated. The objective of this study was to determine if plasma Aß 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) ε4 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 Aß levels were measured in fasting blood samples. A subgroup (n=116) underwent (11)C-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 Aß1-42/1-40 ratio (P=0.001). After stratification of the cohort based on APOE ε4 allele carriage, it was evident that only non-carriers received the benefit of reduced plasma Aß from physical activity. Conversely, lower levels of PiB SUVR (standardised uptake value ratio) were observed in higher exercising APOE ε4 carriers. Lower plasma Aß1-42/1-40 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.

Factors affecting subjective memory complaints in the AIBL aging study: biomarkers, memory, affect, and age.

BACKGROUND: The prognostic value of subjective memory complaints (SMCs) in the diagnosis of dementia of the Alzheimer's type is unclear. While some studies have found an association between SMCs and cognitive decline, many have found a stronger association with depression, which raises questions about their diagnostic utility. METHODS: We examined the cross-sectional association between SMC severity (as measured using the MAC-Q, a brief SMC questionnaire) and affect, memory, and Alzheimer's disease (AD) biomarkers (ß-amyloid deposition and the apolipoprotein E ε4 (APOEε4) allele) in healthy elderly controls (HC; M = 78.74 years, SD = 6.7) and individuals with mild cognitive impairment (MCI; M = 72.74 years, SD = 8.8). We analyzed a subset of individuals drawn from the Australian Imaging Biomarkers and Lifestyle (AIBL) Study of Aging. RESULTS: SMCs were more severe in MCI patients than in HCs. SMC severity was related to affective variables and the interaction between age and group membership (HC/MCI). Within the HC group, SMC severity was related to affective variables only, while severity correlated only with age in the MCI group. SMCs were not related to cognitive variables or AD biomarkers. CONCLUSION: SMCs were related to solely by poorer mood (greater depressive and anxious symptomatology) in the cognitively healthy elderly however mean levels were subclinical. This finding argues for the assessment of affective symptomatology in conjunction with cognitive assessment in elderly memory complainers. Future AIBL research will focus on assessing other AD biomarkers, such as brain atrophy and Aß plasma markers, in relation to complaint severity. Once our 36-month follow-up data are collected, we propose to assess whether SMCs can predict future cognitive decline.

Contrasting perceptions of health professionals and older people in Australia: what constitutes elder abuse?

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. χ(2) analyses indicated that significantly more health professionals than older people identified locking someone in the house alone all day (χ(2) (2) = 10.20, p = 0.006, Cramer's V = 0.14), restraining someone in a chair (χ(2) (2) = 19.984, p = 0.0005, Cramer's V = 0.19) and hiding medication in food (χ(2) (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.

Clearance mechanisms of Alzheimer's amyloid-beta peptide: implications for therapeutic design and diagnostic tests.

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-beta (Abeta) peptide is central to the pathological cascade involved in the pathogenesis of AD. Although Abeta is produced by almost every cell in the body, a physiological function for the peptide has not been determined, and the pathways by which Abeta leads to cognitive dysfunction and cell death are unclear. Numerous therapeutic approaches that target the production, toxicity and removal of Abeta 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 Abeta clearance, transport and degradation, and evaluates the use of such information in the development of diagnostic tools. The conflicting results of plasma Abeta ELISAs are discussed, as are the more promising results of Abeta imaging by positron emission tomography. Current knowledge of Abeta-binding proteins and Abeta-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 Abeta remains an attractive therapeutic strategy, and improved understanding of Abeta clearance may lead to advances in diagnostics and interventions designed to prevent or delay the onset of AD.

Predictors of adherence to atypical antipsychotics (risperidone or olanzapine) in older patients with schizophrenia: an open study of 3(1/2) years duration.

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.

Association between Cognitive Function and Clustered Cardiovascular Risk of Metabolic Syndrome in Older Adults at Risk of Cognitive Decline.

OBJECTIVES: Metabolic syndrome (MetS) represents a cluster of obesity and insulin resistance-related comorbidities. Abdominal obesity, hypertension, elevated triglyceride and glucose levels are components of MetS and may have a negative effect on cognitive function, but few cognitive studies have examined the combined risk severity. We sought to determine which specific cognitive abilities were associated with MetS in older adults at risk of cognitive decline. DESIGN: Cross-sectional study. PARTICIPANTS: 108 AIBL Active participants with memory complaints and at least one cardiovascular risk factor. MEASUREMENTS: Cardiovascular parameters and blood tests were obtained to assess metabolic syndrome criteria. The factors of MetS were standardized to obtain continuous z-scores. A battery of neuropsychological tests was used to evaluate cognitive function. RESULTS: Higher MetS z-scores were associated with poorer global cognition using ADAS-cog (adjusted standardized beta=0.26, SE 0.11, p<0.05) and higher Trail Making B scores (adjusted beta=0.23, SE 0.11, p<0.05). Higher MetS risk was related to lower cognitive performance. CONCLUSION: Combined risk due to multiple risk factors in MetS was related to lower global cognitive performance and executive function. A higher MetS risk burden may point to opportunities for cognitive testing in older adults as individuals may experience cognitive changes.

Integrated care improves risk-factor modification after stroke: initial results of the Integrated Care for the Reduction of Secondary Stroke model.

OBJECTIVE: Despite evidence demonstrating that risk-factor management is effective in reducing recurrent cerebrovascular disease, there are very few structured care programmes for stroke survivors. The aim was to implement and evaluate an integrated care programme in stroke. METHODS: 186 patients with stroke were randomised to either the treatment (integrated care) or control (usual care) group and were followed up over 12 months. The Integrated Care for the Reduction of Secondary Stroke (ICARUSS) model of integrated care involved collaboration between a specialist stroke service, a hospital coordinator and a patient's general practitioner. The primary aim was to promote the management of vascular risk factors through ongoing patient contact and education. RESULTS: In the 12 months poststroke, systolic blood pressure (sBP) decreased in the treatment group but increased in controls. The group difference was significant, and remained so when age, sex, disability and sBP at discharge were accounted for (p = 0.04). Treatment patients also exhibited better modification of body mass index (p = 0.007) and number of walks taken (p<0.001) than controls. Rankin scores indicated significantly reduced disability in treatment patients relative to controls in the year poststroke (p = 0.003). CONCLUSIONS: Through an integrated system of education, advice and support to both patient and GP, the ICARUSS model was effective in modifying a variety of vascular risk factors and therefore should decrease the likelihood or recurrent stroke or vascular event.

FAST-TIA: a prospective evaluation of a nurse-led anterior circulation TIA clinic.

BACKGROUND: Transient ischaemic attacks (TIAs) carry a significant early risk of stroke. New national guidelines state patients should be seen within 7 days of the incident, with higher-risk patients being seen within 24 h. Meeting these targets across the NHS poses a significant challenge. A novel approach to TIA assessment has been developed using a nurse-led rapid-access anterior circulation TIA clinic. METHODS: This was a prospective evaluation of all patients attending the FAST-TIA clinic between November 2003 and December 2006. Diagnostic yield of neurovascular events among patients seen through the TIA service and median time from referral to assessment and from event to assessment were measured. RESULTS: 282 patients were eligible for investigation, and seen through the clinic over a period of 38 months. A vascular event was diagnosed in 242 (86%). TIA was diagnosed in 133 (55%), minor ischaemic stroke in 77 (32%), haemorrhagic stroke in three (1%), and an ocular event in 29 (12%). Median time from referral to assessment was 3 days (interquartile range (IQR) 1-7), and from event to assessment it was 7 days (IQR 3-18). 34% of patients were seen within 24 h of referral. CONCLUSIONS: This model has a high diagnostic rate of 86% vascular events, significantly higher than current national averages of approximately 55%. Current national guidelines for early assessment of patients (published subsequent to this study) are achievable using this service. The FAST-TIA model is an easily reproducible and pragmatic method of improving the diagnostic yield of TIA services, while keeping within national targets.

Application of the NIA-AA Research Framework: Towards a Biological Definition of Alzheimer's Disease Using Cerebrospinal Fluid Biomarkers in the AIBL Study.

BACKGROUND: The National Institute on Aging and Alzheimer's Association (NIA-AA) have proposed a new Research Framework: Towards a biological definition of Alzheimer's disease, which uses a three-biomarker construct: Aß-amyloid, tau and neurodegeneration AT(N), to generate a biomarker based definition of Alzheimer's disease. OBJECTIVES: To stratify AIBL participants using the new NIA-AA Research Framework using cerebrospinal fluid (CSF) biomarkers. To evaluate the clinical and cognitive profiles of the different groups resultant from the AT(N) stratification. To compare the findings to those that result from stratification using two-biomarker construct criteria (AT and/or A(N)). DESIGN: Individuals were classified as being positive or negative for each of the A, T, and (N) categories and then assigned to the appropriate AT(N) combinatorial group: A-T-(N)-; A+T-(N)-; A+T+(N)-; A+T-(N)+; A+T+(N)+; A-T+(N)-; A-T-(N)+; A-T+(N)+. In line with the NIA-AA research framework, these eight AT(N) groups were then collapsed into four main groups of interest (normal AD biomarkers, AD pathologic change, AD and non-AD pathologic change) and the respective clinical and cognitive trajectories over 4.5 years for each group were assessed. In two sensitivity analyses the methods were replicated after assigning individuals to four groups based on being positive or negative for AT biomarkers as well as A(N) biomarkers. SETTING: Two study centers in Melbourne (Victoria) and Perth (Western Australia), Australia recruited MCI individuals and individuals with AD from primary care physicians or tertiary memory disorder clinics. Cognitively healthy, elderly NCs were recruited through advertisement or via spouses of participants in the study. PARTICIPANTS: One-hundred and forty NC, 33 MCI participants, and 27 participants with AD from the AIBL study who had undergone CSF evaluation using Elecsys® assays. INTERVENTION (if any): Not applicable. MEASUREMENTS: Three CSF biomarkers, namely amyloid ß1-42, phosphorylated tau181, and total tau, were measured to provide the AT(N) classifications. Clinical and cognitive trajectories were evaluated using the AIBL Preclinical Alzheimer Cognitive Composite (AIBL-PACC), a verbal episodic memory composite, an executive function composite, California Verbal Learning Test - Second Edition; Long-Delay Free Recall, Mini-Mental State Examination, and Clinical Dementia Rating Sum of Boxes scores. RESULTS: Thirty-eight percent of the elderly NCs had no evidence of abnormal AD biomarkers, whereas 33% had biomarker levels consistent with AD or AD pathologic change, and 29% had evidence of non-AD biomarker change. Among NC participants, those with biomarker evidence of AD pathology tended to perform worse on cognitive outcome assessments than other biomarker groups. Approximately three in four participants with MCI or AD had biomarker levels consistent with the research framework's definition of AD or AD pathologic change. For MCI participants, a decrease in AIBL-PACC scores was observed with increasing abnormal biomarkers; and increased abnormal biomarkers were also associated with increased rates of decline across some cognitive measures. CONCLUSIONS: Increasing biomarker abnormality appears to be associated with worse cognitive trajectories. The implementation of biomarker classifications could help better characterize prognosis in clinical practice and identify those at-risk individuals more likely to clinically progress, for their inclusion in future therapeutic trials.

Recall and recognition of verbal paired associates in early Alzheimer's disease.

The primary impairment in early Alzheimer's disease (AD) is encoding/consolidation, resulting from medial temporal lobe (MTL) pathology. AD patients perform poorly on cued-recall paired associate learning (PAL) tasks, which assess the ability of the MTLs to encode relational memory. Since encoding and retrieval processes are confounded within performance indexes on cued-recall PAL, its specificity for AD is limited. Recognition paradigms tend to show good specificity for AD, and are well tolerated, but are typically less sensitive than recall tasks. Associate-recognition is a novel PAL task requiring a combination of recall and recognition processes. We administered a verbal associate-recognition test and cued-recall analogue to 22 early AD patients and 55 elderly controls to compare their ability to discriminate these groups. Both paradigms used eight arbitrarily related word pairs (e.g., pool-teeth) with varying degrees of imageability. Associate-recognition was equally effective as the cued-recall analogue in discriminating the groups, and logistic regression demonstrated classification rates by both tasks were equivalent. These preliminary findings provide support for the clinical value of this recognition tool. Conceptually it has potential for greater specificity in informing neuropsychological diagnosis of AD in clinical samples but this requires further empirical support.

Dietary Supplement Use in Older People Attending Memory Clinics in Australia.

BACKGROUND: Dietary supplement use is common in older adults. There has been limited research in people attending memory clinics. OBJECTIVES: To explore the use of dietary supplements in older people attending Australian memory clinics. DESIGN: Cross-sectional analysis of baseline data from the Prospective Research In MEmory clinics (PRIME) study. PARTICIPANTS: Community-dwelling older people who attended nine memory clinics and had a diagnosis of mild cognitive impairment (MCI) or dementia. MEASUREMENTS: Dietary supplement was defined as a product that contains one or more: vitamin, mineral, herb or other botanical, amino acid or other dietary substance. Non-prescribed supplement was defined as a supplement that is not usually prescribed by a medical practitioner. Polypharmacy was defined as use of five or more medications. RESULTS: 964 patients, mean age 77.6 years, were included. Dietary supplements were used by 550 (57.1%) patients; 353 (36.6%) used two or more. Non-prescribed supplements were used by 364 (36.8%) patients. Supplement use was associated with older age (OR: 1.12, 95% CI: 1.03-1.21), lower education level (OR: 1.53, 95% CI: 1.01-2.32) and a diagnosis of MCI rather than dementia (OR: 1.52, 95% CI: 1.05-2.21). Potential drug-supplement interactions were identified in 107 (11.1%) patients. Supplement users had increased prevalence of polypharmacy compared to non-users (80.5% vs. 48.1%, p<0.001). CONCLUSIONS: Dietary supplements, including non-prescribed supplements, were commonly used by people attending memory clinics. Supplement use increased the prevalence of polypharmacy and resulted in potential supplement-drug interactions. Further research is required to assess the clinical outcomes of supplement use.

Thyroid, parathyroid, and salivary gland evaluations in patients exposed to multiple fluoroscopic examinations during tuberculosis therapy: a pilot study.

The prevalence of thyroid, parathyroid, and salivary abnormalities was determined in 91 women who received an average of 112 fluoroscopic chest examinations during pneumothorax treatment for tuberculosis more than 40 yr previously and in 72 women treated for tuberculosis by other modalities. Thyroid abnormalities were determined by physical examination, scintiscans, and measurements of serum free T4 index, TSH, and thyroid microsomal antibodies. Thyroid nodules were diagnosed in 7.7% of the exposed and 4.2% of the comparison group (prevalence ratio, 1.8; 90% confidence interval 0.6-5.7). Autoimmune thyroid disease was diagnosed in 15.2% of the exposed and 6.9% of the comparison group (prevalence ratio, 2.2; 95% confidence interval, 0.8-6.2). No salivary tumors were detected. Two exposed women and 1 comparison woman had primary hyperparathyroidism. Although absorbed dose to the thyroid could not be precisely determined, approximately 60 rads would be expected to yield the observed excess of thyroid nodules. While the prevalence ratios were not significantly increased in the exposed group, the results suggest that susceptibility of the thyroid to nodules from cumulative radiation doses of this magnitude could be increased even when the doses are accumulated over years and that such x-ray exposure of the thyroid gland may predispose the patient to the development of autoimmune disease.

Neurologic features and psychopathology in schizophrenic disorders.

Evidence of neurologic disturbance is widely reported in schizophrenic disorders. Few studies have attempted to determine the specificity of these abnormalities to schizophrenic disorders or their relationship to particular psychopathologic features. We assessed neurologic and psychopathologic features in a sample of 53 schizophrenic, 21 affective, and 20 normal subjects. The results indicate that neurologic (motor and sensory) disturbances occur with the highest frequency (92%) and severity in schizophrenic subjects. Affective subjects showed a high frequency (52%) but less severe abnormalities and normal controls had a frequency (5%) comparable to prior reports. Schizophrenic phenomenologic subtypes were not associated with distinguishable patterns of neurologic abnormality. Schizophrenic subjects and affective subjects tend to produce more right sensory errors although few of the latter produced errors. Neurologic abnormalities are highly correlated with evidence of disturbed thinking and cognitive performance. A noteworthy association between disturbed thinking and neurologic motor abnormality was detected in schizophrenic disorders. Anomalous laterality preferences also occur more frequently among schizophrenics and are associated with greater frequency of neurologic disturbance, formal thought disorder, and impaired cognitive performance than among schizophrenics with right laterality preferences.