Cassandra Szoeke

Publications of Cassandra Szoeke

• Cortical surface mapping using topology correction, partial flattening and 3D shape context-based non-rigid registration for use in quantifying atrophy in Alzheimer's disease.

  Authors: Oscar Acosta, Jurgen Fripp, Vincent Doré, Pierrick Bourgeat, Jean-Marie Favreau, Gaël Chételat, Andrea Rueda, Victor L Villemagne, Cassandra Szoeke, David Ames, Kathryn A Ellis, Ralph N Martins, Colin L Masters, Christopher C Rowe, Erik Bonner, Florence Gris, Di Xiao, Parnesh Raniga, Vincent Barra, Olivier Salvado

  Journal of neuroscience methods. 03/2012; 205(1):96-109.

  Magnetic resonance (MR) provides a non-invasive way to investigate changes in the brain resulting from aging or neurodegenerative disorders such as Alzheimer's disease (AD). Performing accurateMagnetic resonance (MR) provides a non-invasive way to investigate changes in the brain resulting from aging or neurodegenerative disorders such as Alzheimer's disease (AD). Performing accurate analysis for population studies is challenging because of the interindividual anatomical variability. A large set of tools is found to perform studies of brain anatomy and population analysis (FreeSurfer, SPM, FSL). In this paper we present a newly developed surface-based processing pipeline (MILXCTE) that allows accurate vertex-wise statistical comparisons of brain modifications, such as cortical thickness (CTE). The brain is first segmented into the three main tissues: white matter, gray matter and cerebrospinal fluid, after CTE is computed, a topology corrected mesh is generated. Partial inflation and non-rigid registration of cortical surfaces to a common space using shape context are then performed. Each of the steps was firstly validated using MR images from the OASIS database. We then applied the pipeline to a sample of individuals randomly selected from the AIBL study on AD and compared with FreeSurfer. For a population of 50 individuals we found correlation of cortical thickness in all the regions of the brain (average r=0.62 left and r=0.64 right hemispheres). We finally computed changes in atrophy in 32 AD patients and 81 healthy elderly individuals. Significant differences were found in regions known to be affected in AD. We demonstrated the validity of the method for use in clinical studies which provides an alternative to well established techniques to compare different imaging biomarkers for the study of neurodegenerative diseases.

• Lifestyle and late life cognitive health: sufficient evidence to act now?

  Authors: Bruce Barber, David Ames, Kathryn Ellis, Ralph Martins, Colin Masters, Cassandra Szoeke

  International psychogeriatrics / IPA. 02/2012; 24(5):683-8.

• Use of the CogState Brief Battery in the assessment of Alzheimer's disease related cognitive impairment in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study.

  Authors: Yen Ying Lim, Kathryn A Ellis, Karra Harrington, David Ames, Ralph N Martins, Colin L Masters, Christopher Rowe, Greg Savage, Cassandra Szoeke, David Darby, Paul Maruff, The Aibl Research Group

  Journal of clinical and experimental neuropsychology. 01/2012;

  The aim of this study was to validate the CogState Brief Battery, which assesses psychomotor, attentional, working memory, and visual learning functions, in healthy older people and in patients withThe aim of this study was to validate the CogState Brief Battery, which assesses psychomotor, attentional, working memory, and visual learning functions, in healthy older people and in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. In healthy older adults, weak relationships between demographic variables (e.g., education, depression) and cognitive performance were observed. In AD and MCI groups, the magnitude of impairment was greatest for tasks of working memory and memory, with a negative influence of apolipoprotein E ϵ4 status on learning but not working memory. These results suggest that the CogState Brief Battery can be used to screen for AD-related cognitive changes.

• Homocysteine, vitamin B12, and folic acid levels in Alzheimer's disease, mild cognitive impairment, and healthy elderly: baseline characteristics in subjects of the Australian Imaging Biomarker Lifestyle study.

  Authors: Noel G Faux, Kathryn A Ellis, Lorine Porter, Chris J Fowler, Simon M Laws, Ralph N Martins, Kelly K Pertile, Alan Rembach, Chris C Rowe, Rebecca L Rumble, Cassandra Szoeke, Kevin Taddei, Tania Taddei, Brett O Trounson, Victor L Villemagne, Vanessa Ward, David Ames, Colin L Masters, Ashley I Bush

  Journal of Alzheimer's disease : JAD. 09/2011; 27(4):909-22.

  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).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.

• Predictors of rapid cognitive decline in Alzheimer's disease: results from the Australian imaging, biomarkers and lifestyle (AIBL) study of ageing.

  Authors: Alessandro Sona, Ping Zhang, David Ames, Ashley I Bush, Nicola T Lautenschlager, Ralph N Martins, Colin L Masters, Christopher C Rowe, Cassandra Szoeke, Kevin Taddei, Kathryn A Ellis

  International psychogeriatrics / IPA. 07/2011; 24(2):197-204.

  The AIBL study, which commenced in November 2006, is a two-center prospective study of a cohort of 1112 volunteers aged 60+. The cohort includes 211 patients meeting NINCDS-ADRDA criteria forThe AIBL study, which commenced in November 2006, is a two-center prospective study of a cohort of 1112 volunteers aged 60+. The cohort includes 211 patients meeting NINCDS-ADRDA criteria for Alzheimer's disease (AD) (180 probable and 31 possible). We aimed to identify factors associated with rapid cognitive decline over 18 months in this cohort of AD patients. We defined rapid cognitive decline as a drop of 6 points or more on the Mini-Mental State Examination (MMSE) between baseline and 18-month follow-up. Analyses were also conducted with a threshold of 4, 5, 7 and 8 points, as well as with and without subjects who had died or were too severely affected to be interviewed at 18 months and after, both including and excluding subjects whose AD diagnosis was "possible" AD. We sought correlations between rapid cognitive decline and demographic, clinical and biological variables. Of the 211 AD patients recruited at baseline, we had available data for 156 (73.9%) patients at 18 months. Fifty-one patients were considered rapid cognitive decliners (32.7%). A higher Clinical Dementia Rating scale (CDR) and higher CDR "sum of boxes" score at baseline were the major predictors of rapid cognitive decline in this population. Furthermore, using logistic regression model analysis, patients treated with a cholinesterase inhibitor (CheI) had a higher risk of being rapid cognitive decliners, as did males and those of younger age. Almost one third of patients satisfying established research criteria for AD experienced rapid cognitive decline. Worse baseline functional and cognitive status and treatment with a CheI were the major factors associated with rapid cognitive decline over 18 months in this population.

• Cognition and beta-amyloid in preclinical Alzheimer's disease: data from the AIBL study.

  Authors: Kerryn E Pike, Kathryn A Ellis, Victor L Villemagne, Norm Good, Gael Chételat, David Ames, Cassandra Szoeke, Simon M Laws, Giuseppe Verdile, Ralph N Martins, Colin L Masters, Christopher C Rowe

  Neuropsychologia. 04/2011; 49(9):2384-90.

  The 'preclinical' phase of Alzheimer's disease is a future target for treatment, but additional research is essential to understand the relationship between β-amyloid burden and cognition during thisThe 'preclinical' phase of Alzheimer's disease is a future target for treatment, but additional research is essential to understand the relationship between β-amyloid burden and cognition during this time. We investigated this relationship using a large sample of apparently healthy older adults (N=177), which also enabled examination of whether the relationship differed according to age, gender, years of education, apolipoprotein E status, and the presence of subjective memory complaints. In addition to episodic memory, a range of cognitive measures (global cognition, semantic memory, visuospatial performance, and executive function) were examined. Participants were aged over 60 years with no objective cognitive impairment and came from the imaging arm of the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study of ageing. (11)C-PiB PET was used to measure β-amyloid burden and a PiB 'cut-off' level of 1.5 was used to separate participants with low PiB retention from those with high PiB retention. Thirty-three percent of participants had a PiB positive scan. PiB positive participants were 5 years older, twice as likely to carry an apolipoprotein E ɛ4 allele, and their composite episodic memory was 0.26 SD worse than PiB negative volunteers. Linear regressions with β-amyloid burden as a dichotomous predictor, revealed an interaction between β-amyloid burden and gender, as well as age and education effects, in predicting episodic memory and visuospatial performance. In females, but not in males, increased β-amyloid was related to worse episodic memory and visuospatial performance. Furthermore, an interaction between β-amyloid burden and APOE status was found in predicting visuospatial performance, whereby there was a trend for increased β-amyloid to relate to worse visuospatial performance for those without an APOE ɛ4 allele. There were no other main or interaction effects of β-amyloid on any of the other composite cognitive measures. These cross-sectional findings suggest that β-amyloid burden does not have a large effect on cognition in this subset of apparently healthy older people. The finding of gender differences deserves further research to answer definitively the important question of gender susceptibility to adverse cognitive effects from β-amyloid.

• Effects of anticholinergic drugs on cognitive function in older Australians: results from the AIBL study.

  Authors: Gobhathai Sittironnarit, David Ames, Ashley I Bush, Noel Faux, Leon Flicker, Jonathan Foster, Sarah Hilmer, Nicola T Lautenschlager, Paul Maruff, Colin L Masters, Ralph N Martins, Christopher Rowe, Cassandra Szoeke, Kathryn A Ellis

  Dementia and geriatric cognitive disorders. 03/2011; 31(3):173-8.

  The nature and extent of adverse cognitive effects due to the prescription of anticholinergic drugs in older people with and without dementia is unclear. We calculated the anticholinergic load (ACL)The nature and extent of adverse cognitive effects due to the prescription of anticholinergic drugs in older people with and without dementia is unclear. We calculated the anticholinergic load (ACL) of medications taken by participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing, a cohort of 211 Alzheimer's disease (AD) patients, 133 mild cognitive impairment (MCI) patients and 768 healthy controls (HC) all aged over 60 years. The association between ACL and cognitive function was examined for each diagnostic group (HC, MCI, AD). A high ACL within the HC group was associated with significantly slower response speeds for the Stroop color and incongruent trials. No other significant relationships between ACL and cognition were noted. In this large cohort, prescribed anticholinergic drugs appeared to have modest effects upon psychomotor speed and executive function, but not on other areas of cognition in healthy older adults.

• Independent contribution of temporal beta-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease.

  Authors: Gaël Chételat, Victor L Villemagne, Kerryn E Pike, Kathryn A Ellis, Pierrick Bourgeat, Gareth Jones, Graeme J O'Keefe, Olivier Salvado, Cassandra Szoeke, Ralph N Martins, David Ames, Colin L Masters, Christopher C Rowe

  Brain : a journal of neurology. 02/2011; 134(Pt 3):798-807.

  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 theThe 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.

• Association of plasma Aß peptides with blood pressure in the elderly.

  Authors: Jean-Charles Lambert, Jean Dallongeville, Kathryn A Ellis, Susanna Schraen-Maschke, James Lui, Simon Laws, Julie Dumont, Florence Richard, Dominique Cottel, Claudine Berr, David Ames, Colin L Masters, Christopher C Rowe, Cassandra Szoeke, Christophe Tzourio, Jean-François Dartigues, Luc Buée, Ralph Martins, Philippe Amouyel

  PloS one. 01/2011; 6(4):e18536.

  Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentativelyAß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Plasma Aß(1-40) and Aß(1-42) levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) and the Australian, longitudinal AIBL study (n = 576). In the combined sample, the Aß(1-42)/ Aß(1-40) ratio was significantly and inversely associated with SBP (p = 0.03) and a similar trend was observed for DBP (p = 0.06). Using the median age (69) as a cut-off, the Aß(1-42)/Aß(1-40) ratio was strongly associated with both SBP and DBP in elderly individuals (p = 0.002 and p = 0.03, respectively). Consistently, a high Aß(1-42)/ Aß(1-40) ratio was associated with a lower risk of hypertension in both the combined whole sample (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.56-0.90) and (to an even greater extent) in the elderly subjects (OR, 0.53; 95% CI, 0.37-0.75). Lastly, all these associations appeared to be primarily driven by the level of plasma Aß(1-40). The plasma Aß(1-42)/Aß(1-40) ratio is inversely associated with SBP, DBP and the risk of hypertension in elderly subjects, suggesting that Aß peptides affect blood pressure in vivo. These results may be particularly relevant in Alzheimer's disease, in which a high Aß(1-42)/Aß(1-40) plasma ratio is reportedly associated with a decreased risk of incident disease.

• Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease.

  Authors: Victor L Villemagne, Kerryn E Pike, Gaël Chételat, Kathryn A Ellis, Rachel S Mulligan, Pierrick Bourgeat, Uwe Ackermann, Gareth Jones, Cassandra Szoeke, Olivier Salvado, Ralph Martins, Graeme O'Keefe, Chester A Mathis, William E Klunk, David Ames, Colin L Masters, Christopher C Rowe

  Annals of neurology. 01/2011; 69(1):181-92.

  Assess Aβ deposition longitudinally and explore its relationship with cognition and disease progression. Clinical follow-up was obtained 20 ± 3 months after [¹¹C]Pittsburgh compound B (PiB)-positronAssess Aβ deposition longitudinally and explore its relationship with cognition and disease progression. 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. 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. 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.

• Larger temporal volume in elderly with high versus low beta-amyloid deposition.

  Authors: Gaël Chételat, Victor L Villemagne, Kerryn E Pike, Jean-Claude Baron, Pierrick Bourgeat, Gareth Jones, Noel G Faux, Kathryn A Ellis, Olivier Salvado, Cassandra Szoeke, Ralph N Martins, David Ames, Colin L Masters, Christopher C Rowe

  Brain : a journal of neurology. 11/2010; 133(11):3349-58.

  β-Amyloid deposition is one of the main hallmarks of Alzheimer's disease thought to eventually cause neuronal death. Post-mortem and neuroimaging studies have consistently reported cases withβ-Amyloid deposition is one of the main hallmarks of Alzheimer's disease thought to eventually cause neuronal death. Post-mortem and neuroimaging studies have consistently reported cases with documented normal cognition despite high β-amyloid burden. It is of great interest to understand what differentiates these particular subjects from those without β-amyloid deposition or with both β-amyloid deposition and cognitive deficits, i.e. what allows these subjects to resist the damage of the pathological lesions. [¹¹C]Pittsburgh compound B positron emission tomography and magnetic resonance brain scans were obtained in 149 participants including healthy controls and patients with subjective cognitive impairment, mild cognitive impairment and Alzheimer's disease. Magnetic resonance data were compared between high versus low-[11C]Pittsburgh compound B cases, and between high-[¹¹C]Pittsburgh compound B cases with versus those without cognitive deficits. Larger temporal (including hippocampal) grey matter volume, associated with better episodic memory performance, was found in high- versus low-[¹¹C]Pittsburgh compound B healthy controls. The same finding was obtained using different [¹¹C]Pittsburgh compound B thresholds, correcting [¹¹C]Pittsburgh compound B data for partial averaging, using age, education, Mini-Mental State Examination, apolipoprotein E4 and sex-matched subsamples, and using manual hippocampal delineation instead of voxel-based analysis. By contrast, in participants with subjective cognitive impairment, significant grey matter atrophy was found in high-[¹¹C]Pittsburgh compound B cases compared to low-[¹¹C]Pittsburgh compound B cases, as well as in high-[¹¹C]Pittsburgh compound B cases with subjective cognitive impairment, mild cognitive impairment and Alzheimer's disease compared to high-[¹¹C]Pittsburgh compound B healthy controls. Larger grey matter volume in high-[¹¹C]Pittsburgh compound B healthy controls may reflect either a tissue reactive response to β-amyloid or a combination of higher 'brain reserve' and under-representation of subjects with standard/low temporal volume in the high-[¹¹C]Pittsburgh compound B healthy controls. Our complementary analyses tend to support the latter hypotheses. Overall, our findings suggest that the deleterious effects of β-amyloid on cognition may be delayed in those subjects with larger brain (temporal) volume.

• Executive functions in recently postmenopausal women: absence of strong association with serum gonadal steroids.

  Authors: Joanne Ryan, Frank Z Stanczyk, Lorraine Dennerstein, Wendy J Mack, Margaret S Clark, Cassandra Szoeke, Victor W Henderson

  Brain research. 11/2010; 1379:199-205.

  It is controversial to what extent endogenous gonadal hormone exposures influence executive functions in midlife women. Participants in the population-based Melbourne Women's Midlife Health ProjectIt is controversial to what extent endogenous gonadal hormone exposures influence executive functions in midlife women. Participants in the population-based Melbourne Women's Midlife Health Project were administered a battery of neuropsychological tests on two occasions 2 years apart. Tests of executive functions were the Trail Making Test (Part B), Tower of London (administered at baseline only), Symbol Digit Modalities Test, Digit Span Backward, and Letter-Number Sequencing. Estrone, free estradiol, and free testosterone levels were measured at the time of the first testing, and analyses were restricted to 147 women aged 56-64 years who had recently undergone natural menopause (mean age of menopause 53 years) and were not using hormone therapy. In multiple linear regression analyses, 2 of 20 baseline associations were significant at an alpha level of 0.05. Estrone concentrations were positively associated with Tower of London performance (p=0.02), and the ratio of free testosterone to free estradiol was positively associated with scores on the Symbol Digit Modalities Test score (p=0.04). No hormone measure was significantly predictive of 2-year change in executive functions performance. Significance levels in these exploratory analyses were unadjusted for multiple comparisons, and observed associations could be due to unique psychometric properties of these particular tasks or due to chance. Sex hormone binding globulin concentrations were unrelated to executive function scores. In recently postmenopausal women not receiving hormone therapy, serum concentrations of estrone, estradiol and testosterone, and the testosterone/estradiol ratio are not strongly associated with executive functions.

• Hormone levels and cognitive function in postmenopausal midlife women.

  Authors: Joanne Ryan, Frank Z Stanczyk, Lorraine Dennerstein, Wendy J Mack, Margaret S Clark, Cassandra Szoeke, Daniel Kildea, Victor W Henderson

  Neurobiology of aging. 09/2010; 33(3):617.e11-22.

  Gonadal hormones may influence cognitive function. Postmenopausal midlife women in the population-based Melbourne Women's Midlife Health Project cohort were administered a comprehensive battery ofGonadal hormones may influence cognitive function. Postmenopausal midlife women in the population-based Melbourne Women's Midlife Health Project cohort were administered a comprehensive battery of neuropsychological tests on two occasions 2 years apart. Participants (n = 148, mean age 60 years) had undergone natural menopause and were not using hormone therapy. Estrone, total and free estradiol, and total and free testosterone levels were measured at time of the first testing. Principal-component analysis identified four cognitive factors. In multiple linear regression analyses, better semantic memory performance was associated with higher total (p = 0.02) and free (p = 0.03) estradiol levels and a lower ratio of testosterone to estradiol (p = 0.007). There were trends for associations between better verbal episodic memory and lower total testosterone (p = 0.08) and lower testosterone/estradiol ratio (p = 0.06). Lower free testosterone levels were associated with greater 2-year improvement on verbal episodic memory (p = 0.04); higher testosterone/estradiol predicted greater semantic memory improvement (p = 0.03). In postmenopausal midlife women, endogenous estradiol and testosterone levels and the testosterone/estradiol ratio are associated with semantic memory and verbal episodic memory abilities.

• Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging.

  Authors: Christopher C Rowe, Kathryn A Ellis, Miroslava Rimajova, Pierrick Bourgeat, Kerryn E Pike, Gareth Jones, Jurgen Fripp, Henri Tochon-Danguy, Laurence Morandeau, Graeme O'Keefe [......] Peter Robins, Oscar Acosta, Nat Lenzo, Cassandra Szoeke, Olivier Salvado, Richard Head, Ralph Martins, Colin L Masters, David Ames, Victor L Villemagne

  Neurobiology of aging. 08/2010; 31(8):1275-83.

  The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, a participant of the worldwide Alzheimer's Disease Neuroimaging Initiative (ADNI), performed (11)C-Pittsburgh Compound B (PiB)The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, a participant of the worldwide Alzheimer's Disease Neuroimaging Initiative (ADNI), performed (11)C-Pittsburgh Compound B (PiB) scans in 177 healthy controls (HC), 57 mild cognitive impairment (MCI) subjects, and 53 mild Alzheimer's disease (AD) patients. High PiB binding was present in 33% of HC (49% in ApoE-epsilon4 carriers vs 21% in noncarriers) and increased with age, most strongly in epsilon4 carriers. 18% of HC aged 60-69 had high PiB binding rising to 65% in those over 80 years. Subjective memory complaint was only associated with elevated PiB binding in epsilon4 carriers. There was no correlation with cognition in HC or MCI. PiB binding in AD was unrelated to age, hippocampal volume or memory. Beta-amyloid (Abeta) deposition seems almost inevitable with advanced age, amyloid burden is similar at all ages in AD, and secondary factors or downstream events appear to play a more direct role than total beta amyloid burden in hippocampal atrophy and cognitive decline.

• Association between temporal lobe P-glycoprotein expression and seizure recurrence after surgery for pharmacoresistant temporal lobe epilepsy.

  Authors: Patrick Kwan, Hiu Ming Li, Eman Al-Jufairi, Rawia Abdulla, Michael Gonzales, Andrew H Kaye, Cassandra Szoeke, Ho Keung Ng, Ka Sing Wong, Terence J O'Brien

  Neurobiology of disease. 08/2010; 39(2):192-7.

  Surgery is recommended for pharmacoresistant temporal lobe epilepsy (TLE), but seizures recur in approximately one third of patients postsurgery. P-glycoprotein is an efflux multidrug transporterSurgery is recommended for pharmacoresistant temporal lobe epilepsy (TLE), but seizures recur in approximately one third of patients postsurgery. P-glycoprotein is an efflux multidrug transporter that is overexpressed in a range of epileptogenic pathologies. We hypothesized that increased expression of P-glycoprotein in the epileptogenic temporal lobe might be a marker for recurrence of pharmacoresistant seizures postsurgery. We performed immunohistochemistry on temporal lobe tissues resected from 69 patients who underwent anterior temporal lobectomy for pharmacoresistant TLE with histopathological proven hippocampal sclerosis. P-glycoprotein expression was rated by three pathologists independently. Patients with seizure recurrence (n=22) had greater number of positively stained capillaries (p=0.001) and higher P-glycoprotein immunoreactive score in capillaries (p=0.002) in the white matter of resected temporal lobe. The differences remained significant in multivariate analysis (p=0.002 and 0.006, respectively). The results suggest that P-glycoprotein expression in temporal lobe may be associated with seizure recurrence after surgery for pharmacoresistant TLE.

• Addressing population aging and Alzheimer's disease through the Australian imaging biomarkers and lifestyle study: collaboration with the Alzheimer's Disease Neuroimaging Initiative.

  Authors: Kathryn A Ellis, Christopher C Rowe, Victor L Villemagne, Ralph N Martins, Colin L Masters, Olivier Salvado, Cassandra Szoeke, David Ames

  Alzheimer's & dementia : the journal of the Alzheimer's Association. 05/2010; 6(3):291-6.

  The Australian Imaging Biomarkers and Lifestyle (AIBL) study is a longitudinal study of 1112 volunteers from healthy, mild cognitive impairment, and Alzheimer's disease (AD) populations who can beThe Australian Imaging Biomarkers and Lifestyle (AIBL) study is a longitudinal study of 1112 volunteers from healthy, mild cognitive impairment, and Alzheimer's disease (AD) populations who can be assessed and followed up for prospective research into aging and AD. AIBL aims to improve understanding of the pathogenesis, early clinical manifestation, and diagnosis of AD, and identify diet and lifestyle factors that influence the development of AD. For AIBL, the magnetic resonance imaging parameters of Alzheimer's Disease Neuroimaging Initiative (ADNI) were adopted and the Pittsuburgh compound B ((11)C-PiB) positron emission tomography (PET) acquisition and neuropsychological tests were designed to permit comparison and pooling with ADNI data. Differences to ADNI include assessment every 18-months, imaging in 25% (magnetic resonance imaging, (11)C-PiB PET but no fluorodeoxyglucose PET), more comprehensive neuropsychological testing, and detailed collection of diet and lifestyle data. AIBL has completed the first 18-month follow-up and is making imaging and clinical data available through the ADNI website. Cross-sectional analysis of baseline data is revealing links between cognition, brain amyloid burden, structural brain changes, biomarkers, and lifestyle.

• Plasma amyloid-beta as a biomarker in Alzheimer's disease: the AIBL study of aging.

  Authors: James K Lui, Simon M Laws, Qiao-Xin Li, Victor L Villemagne, David Ames, Belinda Brown, Ashley I Bush, Karl De Ruyck, Jasmin Dromey, Kathryn A Ellis [......] Mark Rodrigues, Christopher C Rowe, Rebecca Rumble, Cassandra Szoeke, Kevin Taddei, Tania Taddei, Brett Trounson, Vanessa Ward, Ralph N Martins, AIBL Research Group

  Journal of Alzheimer's disease : JAD. 04/2010; 20(4):1233-42.

  Amyloid-beta (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD) and has been postulated as a potential biomarker for AD. However, there is a lack of consensus as to itsAmyloid-beta (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD) and has been postulated as a potential biomarker for AD. However, there is a lack of consensus as to its suitability as an AD biomarker. The objective of this study was to determine the significance of plasma Abeta as an AD biomarker and its relationship with Abeta load and to determine the effect of different assay methods on the interpretation of Abeta levels. Plasma Abeta1-40, Abeta1-42, and N-terminal cleaved fragments were measured using both a commercial multiplex assay and a well-documented ELISA in 1032 individuals drawn from the well-characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Further, Abeta levels were compared to Abeta load derived from positron-emission tomography (PET) with the Pittsburgh compound B (PiB). Lower Abeta1-42 and Abeta1-42/1-40 ratio were observed in patients with AD and inversely correlated with PiB-PET derived Abeta load. However, assay methodology significantly impacted the interpretation of data. The cross-sectional analysis of plasma Abeta isoforms suggests that they may not be sufficient per se to diagnose AD. The value of their measurement in prognosis and monitoring of AD interventions needs further study, in addition to future longitudinal comparisons together with other predictors, which will determine whether plasma Abeta has diagnostic value in a panel of biomarkers.

• Relationship between atrophy and beta-amyloid deposition in Alzheimer disease.

  Authors: Gaël Chételat, Victor L Villemagne, Pierrick Bourgeat, Kerryn E Pike, Gareth Jones, David Ames, Kathryn A Ellis, Cassandra Szoeke, Ralph N Martins, Graeme J O'Keefe, Olivier Salvado, Colin L Masters, Christopher C Rowe

  Annals of neurology. 03/2010; 67(3):317-24.

  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 ofElucidating 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. 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. 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. 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.

• Stroke presenting under 3 hours in patients younger than 18 years of age.

  Authors: Cassandra Szoeke, Christopher Bladin, Anne Gordon, Mark T Mackay

  Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 08/2009;

  We report a 14-year-old girl with a delayed diagnosis of stroke, highlighting one of the most significant obstacles to offering acute thrombolytic therapies in teenagers and children. Feasibility ofWe report a 14-year-old girl with a delayed diagnosis of stroke, highlighting one of the most significant obstacles to offering acute thrombolytic therapies in teenagers and children. Feasibility of treatment is further limited by a lack of dosage and safety data in the paediatric population. Improved community awareness and more rapid recognition of stroke may reduce lag time to diagnosis.

• The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer's disease.

  Authors: Kathryn A Ellis, Ashley I Bush, David Darby, Daniela De Fazio, Jonathan Foster, Peter Hudson, Nicola T Lautenschlager, Nat Lenzo, Ralph N Martins, Paul Maruff, Colin Masters, Andrew Milner, Kerryn Pike, Christopher Rowe, Greg Savage, Cassandra Szoeke, Kevin Taddei, Victor Villemagne, Michael Woodward, David Ames

  International psychogeriatrics / IPA. 06/2009;

  ABSTRACTBackground: The Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging aimed to recruit 1000 individuals aged over 60 to assist with prospective research into Alzheimer'sABSTRACTBackground: The Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging aimed to recruit 1000 individuals aged over 60 to assist with prospective research into Alzheimer's disease (AD). This paper describes the recruitment of the cohort and gives information about the study methodology, baseline demography, diagnoses, medical comorbidities, medication use, and cognitive function of the participants.Methods: Volunteers underwent a screening interview, had comprehensive cognitive testing, gave 80 ml of blood, and completed health and lifestyle questionnaires. One quarter of the sample also underwent amyloid PET brain imaging with Pittsburgh compound B (PiB PET) and MRI brain imaging, and a subgroup of 10% had ActiGraph activity monitoring and body composition scanning.Results: A total of 1166 volunteers were recruited, 54 of whom were excluded from further study due to comorbid disorders which could affect cognition or because of withdrawal of consent. Participants with AD (211) had neuropsychological profiles which were consistent with AD, and were more impaired than participants with mild cognitive impairment (133) or healthy controls (768), who performed within expected norms for age on neuropsychological testing. PiB PET scans were performed on 287 participants, 100 had DEXA scans and 91 participated in ActiGraph monitoring.Conclusion: The participants comprising the AIBL cohort represent a group of highly motivated and well-characterized individuals who represent a unique resource for the study of AD. They will be reassessed at 18-month intervals in order to determine the predictive utility of various biomarkers, cognitive parameters and lifestyle factors as indicators of AD, and as predictors of future cognitive decline.