Paul Maruff

Columbia University, New York, New York, United States

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Publications (418)2017.93 Total impact

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    ABSTRACT: Background: Postoperative cognitive dysfunction (POCD) affects 16 to 21% of the elderly 3 months after anesthesia and surgery and is associated with adverse outcomes. The exact cause of POCD remains unknown. The authors hypothesized that elderly individuals with Alzheimer disease (AD) neuropathology, identified by cerebrospinal fluid (CSF) analysis, would have increased the risk for POCD. Methods: CSF samples were collected from 59 patients 60 yr or older who received combined spinal and general anesthesia for elective total hip replacement. Patients underwent neuropsychological testing preoperatively and at 7 days, 3 months, and 12 months postoperatively. POCD at 3 months and cognitive decline at 12 months were calculated by using the reliable change index. CSF amyloid β1-42 (Aβ1-42), total-tau, phosphorylated-tau, and neurofilament light were assayed with enzyme-linked immunosorbent assay methods. Results: POCD was identified in 5 of 57 patients (8.8%) at 3 months. For Aβ1-42, 11 patients were below the cut-point for AD neuropathology of whom 3 were classified with POCD (27.3%; 95% CI, 6.0 to 61%), whereas of the 46 patients above the cut-point, 2 were classified with POCD (4.3%; 95% CI, 0.5 to 14.8%) (P = 0.01). There was no significant difference in the incidence of POCD in relation to the cut-points for any of the other analytes. Conclusions: Low CSF Aβ1-42 may be a significant predictor of POCD at 3 months. This indicates that patients with AD neuropathology even in the absence of clinically detectable AD symptoms may be susceptible to POCD.
    Anesthesiology 11/2015; DOI:10.1097/ALN.0000000000000953 · 5.88 Impact Factor
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    ABSTRACT: Background: information provided by an informant about a patient with cognitive change is an essential component of clinical history taking. How an informant's report relates to the patient's phenomenological experience of memory loss is yet to be understood. The aim was to examine patterns of relationships between self and informant reports from a phenomenological perspective. Methods: forty-three healthy non-memory complainers (HC-NMC), 37 healthy subjective memory complainers (HC-SMC) and 43 individuals with mild cognitive impairment (MCI) were administered a semi-structured interview, which measured their concerns of frequency of memory lapses and impact on mood. Informants responded to questionnaires. Results: self-reported concerns of increasing frequency and impacted mood related to informant concerns in HC-SMCs. MCI with lower informant concern showed a similar pattern to HC-SMCs on complaints of increasing frequency. In those with higher informant concern, self-reports markedly separated from informant concern. The MCI group with greater informant concern performed comparatively poor on verbal and non-verbal memory measures. Conclusions: our results suggest that the association between self-reported and informant memory concerns is moderated by MCI severity. Self and informant reports of increasing memory lapse frequency aligned in HC-SMC and MCIs with low informant concern, suggesting a similar dyadic experience of memory change. In MCIs with greater informant concern, the pattern changed exposing a changing insight with advancing memory impairment. These individuals are potentially reflecting a 'forgetting that they forget' phenomenon in elements of their concern.
    Age and Ageing 10/2015; DOI:10.1093/ageing/afv136 · 3.64 Impact Factor
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    ABSTRACT: High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.
    PLoS ONE 10/2015; 10(10):e0139082. DOI:10.1371/journal.pone.0139082 · 3.23 Impact Factor
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    ABSTRACT: Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844-852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures- approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes.
    Journal of Alzheimer's disease: JAD 09/2015; 48(s1). DOI:10.3233/JAD-150154 · 4.15 Impact Factor
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    ABSTRACT: FFQ are commonly used to examine the association between diet and disease. They are the most practical method for usual dietary data collection as they are relatively inexpensive and easy to administer. In Australia, the Cancer Council of Victoria FFQ (CCVFFQ) version 2 and the online Commonwealth Scientific and Industrial Research Organisation FFQ (CSIROFFQ) are used. The aim of our study was to establish the level of agreement between nutrient intakes captured using the online CSIROFFQ and the paper-based CCVFFQ. The CCVFFQ and the online CSIROFFQ were completed by 136 healthy participants. FFQ responses were analysed to give g per d intake of a range of nutrients. Agreement between twenty-six nutrient intakes common to both FFQ was measured by a variety of methods. Nutrient intake levels that were significantly correlated between the two FFQ were carbohydrates, total fat, Na and MUFA. When assessing ranking of nutrients into quintiles, on average, 56 % of the participants (for all nutrients) were classified into the same or adjacent quintiles in both FFQ, with the highest percentage agreement for sugar. On average, 21 % of participants were grossly misclassified by three or four quintiles, with the highest percentage misclassification for fibre and Fe. Quintile agreement was similar to that reported by other studies, and we concluded that both FFQ are suitable tools for dividing participants' nutrient intake levels into high- and low-consumption groups. Use of either FFQ was not appropriate for obtaining accurate estimates of absolute nutrient intakes.
    The British journal of nutrition 09/2015; 114(10):1-11. DOI:10.1017/S0007114515003335 · 3.45 Impact Factor
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    ABSTRACT: Disruption in cholinergic neurotransmission is one of the earliest neuropathological changes in preclinical Alzheimer's disease (AD) and may be associated with abnormal beta-amyloid (Aβ) accumulation. Therefore, disruption of cholinergic neurotransmission with scopolamine may unmask otherwise undetectable cognitive deficits in preclinical AD. To compare the effects of low-dose (0.20 mg s.c.) scopolamine on cognition between Aβ+ and Aβ- cognitively normal (CN) older adults using the Groton Maze Learning Test (GMLT). CN older adults completed the GMLT predose and then received scopolamine (0.20 mg) subcutaneously. Participants were reassessed 1-, 3-, 5-, 7-, and 8-hours post dose. All participants underwent positron emission tomography neuroimaging for Aβ using (18)F-florbetapir within 6 weeks of their baseline visit. Rhode Island Hospital Clinical Research Center, Providence, USA. CN older adults (n = 63), with a family history of AD and subjective memory complaints were enrolled (15 were classified as Aβ+ and 48 were classified as Aβ-). Cognition was assessed using the computerized GMLT at all predose and post-dose time points. At 5-hours post dose, the Aβ+ group performed significantly worse than the Aβ- group on all measures of learning efficiency and working memory and/or executive function (Cohen's d = 1.13-1.56). When participants were classified as having an abnormal response to scopolamine (based on change score at 5-hours post dose >0), 100% were correctly classified as Aβ+ and 67% as Aβ-. The results of this study suggest that diminished cholinergic tone likely occurs in preclinical AD, and as such, the use of a cholinergic stress test to perturb an already compromised neurotransmitter system may be an effective way of identifying CN older adults who are in this preclinical stage of AD. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 07/2015; 36(10). DOI:10.1016/j.neurobiolaging.2015.07.009 · 5.01 Impact Factor
  • Elizabeth Thomas · Paul Maruff · Jacob Paul · Robert Reeve ·
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    ABSTRACT: The stepping-stone variant of the hidden pathway maze learning (HPML) task paradigm has been extensively used to investigate cognitive functions in neuropsychology and neuropharmacology. Previous studies have used total error across trials, as well as rule-break errors and learning errors, to define spatial memory and/or executive function in healthy and impaired adults and children. However, the construct validity of performance measures on HPML tasks has not been established in healthy children. To assess the construct validity of measures of exploratory and rule-break errors on the Groton Maze Learning Task (GMLT) measures of spatial sequence memory (Corsi Blocks Task) and spatial error monitoring (Continuous Paired Associate Learning; CPAL) were used. The results indicate that Corsi span predicted GMLT spatial sequence memory and CPAL accuracy predicted GMLT spatial error monitoring. The construct validity of the GMLT as a measure of spatial memory and executive function are discussed with regard to prior research using HPML tasks in neuropsychological contexts.
    Child Neuropsychology 06/2015; DOI:10.1080/09297049.2015.1038989 · 2.42 Impact Factor
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    ABSTRACT: To better understand the nature and rate of cognitive change across adolescence, the Cogstate Brief Battery (CBB) was utilized to assess psychomotor function, attention, working memory, and visual learning in individuals aged 10 to 18 years old. Since all CBB tasks have equivalent perceptual, motor, and linguistic demands as well as being appropriate for both children and adults, this approach allowed direct across-age comparison of multiple cognitive domains. Exponential decreases in reaction time and linear increases in accuracy were observed across adolescent development in a cross-sectional sample of 38,778 individuals and confirmed in a 5,788 individual longitudinal sample with one-year repeat assessments. These results have important implications for the repeated assessment of cognition during development where expected maturational changes in cognition must be accounted for during cognitive testing.
    Frontiers in Psychology 05/2015; 6. DOI:10.3389/fpsyg.2015.00704 · 2.80 Impact Factor
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    ABSTRACT: Repeat cognitive assessment comparing post-injury performance to a pre-injury baseline is common in concussion management. Although post-injury tests are typically administered in clinical settings, baseline tests may be conducted individually with one-on-one supervision, in a group with supervision, or without supervision. The extent to which these different test settings affect cognitive performance is not well understood. To assess if performance on the Cogstate Brief Battery (CBB) differs across these settings, tests completed individually with one-on-one supervision were compared to those taken either in a group with supervision or individually but without supervision. A crossover study design was utilized to account for any effect of individual variability or test order to provide an unbiased examination of the effect of test setting on cognitive performance. Young adult participants completed an individually supervised test either before or after also completing a group or unsupervised test. CBB scores from the same individuals were not significantly different across test settings. Effect sizes ranged in magnitude from .09 to .12 for supervised versus unsupervised tests and from .01 to .37 for individual versus group tests across CBB tasks. These results suggest that cognitive testing with the CBB in alternate settings can provide valid cognitive data comparable to data obtained during individually supervised testing.
    The Clinical Neuropsychologist 05/2015; 29(4):542-58. DOI:10.1080/13854046.2015.1054437 · 1.72 Impact Factor
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    ABSTRACT: This study investigated the prevalence of cognitive impairment in elderly noncardiac surgery patients and any association between preoperative cognitive impairment and postoperative cognitive dysfunction (POCD). Additionally, the incidence of cognitive decline at 12 months after surgery was identified. Three hundred patients for hip joint replacement and 51 nonsurgical controls aged 60 yr or older were studied in a prospective observational clinical trial. All study participants and controls completed a battery of eight neuropsychological tests before surgery and at 7 days, 3 months, and 12 months afterwards. Preoperative cognitive status was assessed using preexisting cognitive impairment (PreCI) defined as a decline of at least 2 SD on two or more of seven neuropsychological tests compared to population norms. POCD and cognitive decline were assessed using the reliable change index utilizing the results of the control group. PreCI was classified in 96 of 300 (32%) patients (95% CI, 23 to 43%). After surgery, 49 of 286 (17%) patients (95% CI, 13 to 22%) and 27 of 284 (10%) patients (95% CI, 6 to 13%) demonstrated POCD at 7 days and 3 months, respectively, while 7 of 271 (3%) patients (95% CI, 1 to 4%) demonstrated cognitive decline at 12 months. Patients with PreCI had a significantly increased incidence of POCD at 7 days and 3 months and cognitive decline at 12 months. Patients with PreCI have an increased incidence of POCD and cognitive decline. PreCI is a good predictor of subsequent POCD and cognitive decline. The incidence of cognitive decline after 12 months in this group of patients is low.
    Anesthesiology 04/2015; 122(6). DOI:10.1097/ALN.0000000000000671 · 5.88 Impact Factor
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    12th International Conference on Alzheimer's and Parkinson's Disease, Nice, France; 03/2015
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    ABSTRACT: This Phase II exploratory study assessed GSK239512, a brain penetrant histamine H3 receptor antagonist, versus placebo on cognitive impairment in 50 stable outpatients with schizophrenia. Subjects were randomized to placebo or GSK239512 for 7weeks (4weeks titration). GSK239512 was associated with a small positive effect size (ES) on the CogState Schizophrenia Battery (CSSB) Composite Score (ES=0.29, CI=-0.40, 0.99) relative to placebo (primary endpoint). GSK239512's ES on CSSB domains were generally positive or neutral except Processing Speed, which favored placebo (ES=-0.46). Effects on the MATRICS Consensus Cognitive Battery were mostly neutral or favored placebo. GSK239512 was generally well tolerated with an adverse event profile consistent with the known class pharmacology. There was no evidence of overall beneficial effects of GSK239512 for CIAS in this population. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 02/2015; 164(1-3). DOI:10.1016/j.schres.2015.01.041 · 3.92 Impact Factor
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    ABSTRACT: Objective: To explore the subjective experience of memory change in groups at risk of dementia (those with mild cognitive impairment MCI or high β-amyloid (Aβ+) burden) to determine the existence of potential phenomenological typologies. Method: We recruited 123 healthy controls (HC) and individuals with MCI from the Australian Imaging, Biomarker and Lifestyle (AIBL) study. Sixty-7 (HC = 47,MCI = 20) had Aβ scans available for analysis. Semistructured interviews were administered, transcribed, and meaningful phrases extracted from transcripts. Twelve themes were defined and compared across diagnostic status and Aβ status. Results: MCI endorsed more complaints of burdensome coping strategies, increasing frequency, sense of predomination, poor contextualization, progression, dependency, impact on affect, and dismissive attitudes. HCAβ+ acknowledged a progressive memory decline compared to HCAβ-, while MCIAβ+ expressed more burdensome coping strategies, dismissive attitudes, and dependency comparative to either healthy group. Depression was more likely to be related to complaint themes in HCs, while complaint themes were associated with poorer list-learning performance in individuals with MCI. Conclusion: Complaint themes in those with MCI align with the MCI symptom complex, particularly when accompanied with high Aβ load. Healthy Aβ+ individuals acknowledged progressive memory change, suggesting they are aware of memory changes not yet detectable via neuropsychological measures. Depressive symptomatology associated with HC complaints, suggesting certain themes are affect-driven, while complaints in MCI are associated with organically driven functional impairment. Qualitative analysis of SMCs can inform the earliest clinical manifestations of Alzheimer's disease. Our findings can inform diagnostic approaches to the clinical evaluation of memory complaints in the nondemented elderly.
    Neuropsychology 02/2015; 29(4). DOI:10.1037/neu0000156 · 3.27 Impact Factor
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    ABSTRACT: AZD6280 is a novel γ-aminobutyric acid A receptor modulator with higher in vitro efficacy at the α2,3 subtypes as compared to the α1 and α5 subtypes. This study compared the pharmacodynamic effects of single oral dose AZD6280 10 mg and 40 mg on the central nervous system with 2 mg of lorazepam. Sixteen healthy males were enrolled into the double-blind, randomized, 4-way crossover study. Two validated central nervous system test batteries, Neurocart and CogState, were administered to measure drug effects on cognition, neurophysiologic function, and psychomotor and subjective feelings. Statistical analysis was performed using mixed model analysis of variance, with fixed factors of treatment, period, time and treatment by time, and random factors of subject, subject by treatment and subject by time, and the average prevalue as covariate. Most pharmacodynamic parameters were affected by lorazepam. AZD6280 induced dose-dependent smaller-than-lorazepam effects on saccadic peak velocity (SPV) (AZD6280, 10 mg vs. AZD6280, 40 mg vs. lorazepam [deg/s]: -22.6 vs. -50.0 vs. -62.9, P < 0.001), whereas the impacts on adaptive-tracking, body-sway, smooth-pursuit, and the one-card-learning tests were significant but much smaller than lorazepam. Thus, the slopes of regression lines for the ΔLog(Sway)-ΔSPV, ΔTracking-ΔSPV, and ΔSmooth-ΔSPV relations were flatter with AZD6280 than with lorazepam. AZD6280 caused a distinct electroencephalography signature from that of lorazepam. The SPV responses to AZD6280 suggest potential concentration-related anxiolytic effects, whereas the smaller SPV-normalized effects of AZD6280 on various non-SPV pharmacodynamic parameters suggest a more favorable side effect profile compared to lorazepam. Overall, the pharmacodynamic profile of AZD6280 matches the pharmacological specificity and selectivity of this compound at the α2,3 γ-aminobutyric acid A receptor subtypes.
    Journal of Clinical Psychopharmacology 02/2015; 35(1):22-33. DOI:10.1097/JCP.0000000000000251 · 3.24 Impact Factor
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    ABSTRACT: Alzheimer disease (AD) is now known to have a long preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms. Although the presence of abnormal levels of amyloid-β (Aβ) is associated with higher rates of progression to clinically classified mild cognitive impairment or dementia, little research has evaluated potentially modifiable moderators of Aβ-related cognitive decline, such as anxiety and depressive symptoms. To evaluate the association between Aβ status and cognitive changes, and the role of anxiety and depressive symptoms in moderating Aβ-related cognitive changes in the preclinical phase of AD. In this multicenter, prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments, we studied 333 healthy, older adults at hospital-based research clinics. Carbon 11-labeled Pittsburgh Compound B (PiB)-, florbetapir F 18-, or flutemetamol F 18-derived measures of Aβ, Hospital Anxiety and Depression Scale scores, and comprehensive neuropsychological evaluation that yielded measures of global cognition, verbal memory, visual memory, attention, language, executive function, and visuospatial ability. A positive Aβ (Aβ+) status at baseline was associated with a significant decline in global cognition, verbal memory, language, and executive function, and elevated anxiety symptoms moderated these associations. Compared with the Aβ+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the Aβ+, high-anxiety group, with Cohen d values of 0.78 (95% CI, 0.33-1.23) for global cognition, 0.54 (95% CI, 0.10-0.98) for verbal memory, 0.51 (95% CI, 0.07-0.96) for language, and 0.39 (95% CI, 0.05-0.83) for executive function. These effects were independent of age, educational level, IQ, APOE genotype, subjective memory complaints, vascular risk factors, and depressive symptoms; furthermore, depressive symptoms and subjective memory complaints did not moderate the association between Aβ and cognitive decline. These results provide additional support for the deleterious effect of elevated Aβ levels on cognitive function in preclinical AD. They further suggest that elevated anxiety symptoms moderate the effect of Aβ on cognitive decline in preclinical AD, resulting in more rapid decline in several cognitive domains. Given that there is currently no standard antiamyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD.
    JAMA Psychiatry 01/2015; 72(3). DOI:10.1001/jamapsychiatry.2014.2476 · 12.01 Impact Factor
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    ABSTRACT: Memory changes in preclinical Alzheimer's disease (AD) are often characterized by heterogenous trajectories. However, data regarding the nature and determinants of predominant trajectories of memory changes in preclinical AD are lacking. We analyzed data from 333 cognitively healthy older adults who participated in a multicenter prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments. Latent growth mixture modeling revealed 3 predominant trajectories of memory change: a below average, subtly declining memory trajectory (30.9%); a below average, rapidly declining memory trajectory (3.6%); and an above average, stable memory trajectory (65.5%). Compared with the stable memory trajectory, high Αβ (relative risk ratio [RRR] = 2.1), and lower Mini-Mental State Examination (RRR = 0.6) and full-scale IQ (RRR = 0.9) scores were independently associated with the subtly declining memory trajectory; and high Αβ (RRR = 8.3), APOE ε4 carriage (RRR = 6.1), and greater subjective memory impairment (RRR = 1.2) were independently associated with the rapidly declining memory trajectory. Compared with the subtly declining memory trajectory group, APOE ε4 carriage (RRR = 8.4), and subjective memory complaints (RRR = 1.2) were associated with a rapidly declining memory trajectory. These results suggest that the preclinical phase of AD may be characterized by 2 predominant trajectories of memory decline that have common (e.g., high Αβ) and unique (e.g., APOE ε4 genotype) determinants. Published by Elsevier Inc.
    Neurobiology of Aging 12/2014; 36(3). DOI:10.1016/j.neurobiolaging.2014.12.015 · 5.01 Impact Factor
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    ABSTRACT: The apolipoprotein E (APOE) ɛ4 allele and high levels of beta-amyloid (Aβ) are associated with episodic memory decline and risk for Alzheimer's disease. However, there is debate about independent or interactive effects of ɛ4 on Aβ-related memory decline in healthy older adults. Healthy older adults with high Aβ burden (n = 84) enrolled in Australian Imaging, Biomarkers, and Lifestyle Study were included in this study. Cognition was measured using the computerized Cogstate Brief Battery at baseline, 18-, 36-, and 54-month follow-ups. Mini Mental State Examination and Clinical Dementia Rating scales were also administered at baseline and each follow-up timepoint. Relative to Aβ+ ɛ4 noncarriers (n = 36), Aβ+ ɛ4 carriers (n = 48) showed significantly faster decline on memory tasks, which was by convention, moderate in magnitude (d = 0.40-0.47). Aβ positivity coupled with APOE ɛ4 was associated with moderately increased decline in memory over a 54-month assessment period, suggesting that, in the preclinical stages of Alzheimer's disease, the manifestation of memory decline in older adults with high Aβ is exacerbated by the presence of APOE ɛ4. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of Aging 12/2014; 36(3). DOI:10.1016/j.neurobiolaging.2014.12.008 · 5.01 Impact Factor
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    ABSTRACT: Assessment of risk and early diagnosis of Alzheimer's disease (AD) is a key to its prevention or slowing the progression of the disease. Previous research on risk factors for AD typically utilizes statistical comparison tests or stepwise selection with regression models. Outcomes of these methods tend to emphasize single risk factors rather than a combination of risk factors. However, a combination of factors, rather than any one alone, is likely to affect disease development. Genetic algorithms (GA) can be useful and efficient for searching a combination of variables for the best achievement (eg. accuracy of diagnosis), especially when the search space is large, complex or poorly understood, as in the case in prediction of AD development. Multiple sets of neuropsychological tests were identified by GA to best predict conversions between clinical categories, with a cross validated AUC (area under the ROC curve) of 0.90 for prediction of HC conversion to MCI/AD and 0.86 for MCI conversion to AD within 36 months. This study showed the potential of GA application in the neural science area. It demonstrated that the combination of a small set of variables is superior in performance than the use of all the single significant variables in the model for prediction of progression of disease. Variables more frequently selected by GA might be more important as part of the algorithm for prediction of disease development.
    BMC Bioinformatics 12/2014; 15(Suppl 16):S11. DOI:10.1186/1471-2105-15-S16-S11 · 2.58 Impact Factor
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    ABSTRACT: Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60-85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [(18)F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults.
    Translational Research 12/2014; 4(e487). DOI:10.1038/tp.2014.122 · 5.03 Impact Factor
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    ABSTRACT: We investigated the extent to which decline in memory and working memory in beta-amyloid (Aβ) positive non-demented individuals was related to hippocampal atrophy and Aβ accumulation over 36 months. Cognitively normal older adults (CN) (n = 178) and adults with mild cognitive impairment (MCI) (n = 49) underwent positron emission tomography neuroimaging, magnetic resonance imaging, and cognitive assessments at baseline, 18- and 36-months. Relative to Aβ- CNs, Aβ+ CNs and Aβ+ MCIs showed greater rates of cognitive decline, Aβ accumulation, and hippocampal atrophy. Analysis of interrelationships between these Alzheimer's disease markers in Aβ+ CNs and MCIs indicated that rate of Aβ accumulation was associated with rate of hippocampal atrophy (β = -0.05, p = .037), which was in turn associated independently with rate of decline in memory (β = -0.03, p = .032). This suggests that Aβ accumulation precedes any neurodegeneration or clinical symptoms, and that the relationship between Aβ and cognitive decline is mediated by hippocampal atrophy. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail:
    Archives of Clinical Neuropsychology 12/2014; 30(1). DOI:10.1093/arclin/acu068 · 1.99 Impact Factor

Publication Stats

12k Citations
2,017.93 Total Impact Points


  • 2015
    • Columbia University
      New York, New York, United States
  • 2013-2015
    • The Florey Institute of Neuroscience and Mental Health
      Melbourne, Victoria, Australia
  • 1999-2015
    • University of Melbourne
      • • Florey Institute of Neuroscience and Mental Health
      • • Department of Psychiatry
      • • Melbourne School of Psychological Sciences
      Melbourne, Victoria, Australia
  • 2014
    • St George Hospital
      Sydney, New South Wales, Australia
  • 2009-2014
    • Victoria University Melbourne
      Melbourne, Victoria, Australia
    • Charles Darwin University
      • Institute of Advanced Studies
      Palmerston, Northern Territory, Australia
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
    • University of Victoria
      Victoria, British Columbia, Canada
  • 2012
    • Australian Catholic University
      • Faculty of Arts and Sciences
      Melbourne, Victoria, Australia
  • 1999-2012
    • La Trobe University
      • School of Psychological Science
      Melbourne, Victoria, Australia
  • 2011
    • Federal University of Minas Gerais
      Cidade de Minas, Minas Gerais, Brazil
    • The Australian e-Health Research Centre
      Brisbane, Queensland, Australia
  • 2006-2010
    • UNIP Australia Pty Ltd
      Blackburn North, Victoria, Australia
    • University of Connecticut
      • Department of Psychology
      Storrs, Connecticut, United States
    • St Vincent's Health Australia
      Bondi Junction, New South Wales, Australia
  • 2001-2010
    • St. Vincent's Hospital Melbourne
      • Department of Anaesthesia
      Melbourne, Victoria, Australia
    • Bendigo Psychology
      Bendigo, Victoria, Australia
  • 2008
    • RMIT University
      • Department of Psychology
      Melbourne, Victoria, Australia
    • Queen's University Belfast
      Béal Feirste, Northern Ireland, United Kingdom
  • 1991-2006
    • Mental Health Research Institute
      Melbourne, Victoria, Australia
  • 2005
    • St. Vincent Hospital
      Green Bay, Wisconsin, United States
  • 2000-2004
    • Universität Heidelberg
      • Department of Geriatric Psychiatry
      Heidelburg, Baden-Württemberg, Germany
  • 1998-2004
    • Swinburne University of Technology
      Melbourne, Victoria, Australia
  • 2003
    • London Research Institute
      Londinium, England, United Kingdom
  • 2002
    • The University of Western Ontario
      London, Ontario, Canada
  • 1997-1998
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia