Anatomy and Neuroscience - Research Publications

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    Within subject rise in serum TNFα to IL-10 ratio is associated with poorer attention, decision-making and working memory in jockeys.
    Piantella, S ; O'Brien, WT ; Hale, MW ; Maruff, P ; McDonald, SJ ; Wright, BJ (Elsevier BV, 2022-05)
    Jockeys work in high-risk environments that rely heavily on attention- and decision-making to perform well and safely. Workplace stress literature has often overlooked the impact of stress on cognition, and designs that include physiological measures are rare. This study assessed the prospective concurrent relationships between workplace stress, depression symptoms and low-grade inflammation with cognitive performance among professional jockeys. Professional jockeys (N = 35, Mage = 32.29) provided information on workplace stress and depression symptoms, with serum levels of inflammatory cytokines (IL-6, IL-10, TNFα) and cytokine balance (IL-6: IL-10, TNFα: IL-10) quantified with SIMOA, and cognitive performance with CogSport computer-based testing battery. These measures were repeated after a twelve-month interval. Increased workplace stress between testing intervals was associated to an increased cytokine imbalance (β = 0.447, p = .015) after controlling for age and gender. Increases in cytokine imbalance occurred in unison with decreases in attention (β = 0.516, p = .002), decision-making (β = 0.452, p = .009) and working memory (β = 0.492, p = .004). These preliminary findings suggest the underlying mechanisms linking workplace stress and reduced cognitive performance may be influenced by measures of low-grade inflammation and specifically a cytokine imbalance. Our findings suggest a measure of cytokine balance may explain the heterogenous findings in previous studies that have focussed solely on the association of workplace stress with pro-inflammatory cytokines. Future work is needed however, to provide a broader evidence-base for our claims to better inform designs to intervene in the higher workplace stress-poorer cognition relationship.
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    Unsupervised Performance of the CogState Brief Battery in the Brain Health Registry: Implications for Detecting Cognitive Decline.
    Banh, T ; Jin, C ; Neuhaus, J ; Mackin, RS ; Maruff, P ; Stricker, N ; Weiner, MW ; Nosheny, RL (SERDI, 2022)
    INTRODUCTION: The feasibility and validity of unsupervised, longitudinal brief computerized cognitive batteries is unknown. METHODS: Participants aged 56-90 (N = 19476) from the Brain Health Registry (BHR) completed the CogState Brief Battery (CBB) at 6-month intervals over a period of 5 years. We used linear mixed-effects models to assess whether cross-sectional and longitudinal performance on CBB within BHR was associated with demographic and cognitive characteristics. We also defined a group of CBB decliners based on subject-specific slopes and estimated associations between decliner status and participant characteristics. RESULTS: We found weak associations between longitudinal change in CBB and participant characteristics. Cross-sectional CBB scores were significantly associated with participant characteristics such as age, gender, ethnicity, self-reported disease status, and memory concern. CBB decliners were more likely to self-report mild cognitive impairment (MCI) and memory concerns. DISCUSSION: Cross-sectional, remote CBB shows evidence of construct validity, but our results suggest that longitudinal assessment may not provide additional value for identifying those at risk for and with cognitive impairment.
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    No Influence of Age-Related Hearing Loss on Brain Amyloid-beta
    Sarant, JZ ; Harris, DC ; Busby, PA ; Fowler, C ; Fripp, J ; Masters, CL ; Maruff, P ; Bendlin, B (IOS PRESS, 2022-01-01)
    BACKGROUND: Hearing loss is independently associated with a faster rate of cognitive decline in older adults and has been identified as a modifiable risk factor for dementia. The mechanism for this association is unknown, and there has been limited exploration of potential casual pathology. OBJECTIVE: Our objective was to investigate whether there was an association between degree of audiometrically measured hearing loss (HL) and brain amyloid-β (Aβ) in a pre-clinical sample. METHODS: Participants of the Australian Imaging and Biomarker Longitudinal Study (AIBL; n = 143) underwent positron emission tomography (PET) imaging and objective measurement of hearing thresholds within 5 years of imaging, as well as cognitive assessment within 2 years of imaging in this observational cohort study. RESULTS: With one exception, study participants who had cognitive assessments within 2 years of their PET imaging (n = 113) were classified as having normal cognition. There was no association between cognitive scores and degree of hearing loss, or between cognitive scores and Aβ load. No association between HL and Aβ load was found once age was controlled for. As previously reported, positive Apolipoprotein E4 (APOE4) carrier status increased the risk of being Aβ positive (p = 0.002). CONCLUSION: Degree of HL was not associated with positive Aβ status.
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    Longitudinal Association of Intraindividual Variability With Cognitive Decline and Dementia: A Meta-Analysis
    Mumme, R ; Pushpanathan, M ; Donaldson, S ; Weinborn, M ; Rainey-Smith, SR ; Maruff, P ; Bucks, RS (AMER PSYCHOLOGICAL ASSOC, 2021-10-01)
    OBJECTIVE: Intraindividual variability (IIV)-variance in an individual's cognitive performance-may be associated with subsequent cognitive decline and/or conversion to dementia in older adults. This novel measure of cognition encompasses two main operationalizations: inconsistency (IIV-I) and dispersion (IIV-D), referring to variance within or across tasks, respectively. Each operationalization can also be measured with or without covariates. This meta-analytic study explores the association between IIV and subsequent cognitive outcomes regardless of operational definition and measurement approach. METHOD: Longitudinal studies (N = 13) that have examined IIV in association with later cognitive decline and/or conversation to MCI/dementia were analyzed. The effect of IIV operationalization was explored. Additional subgroup analysis of measurement approaches could not be examined due to the limited number of appropriate studies available for inclusion. RESULTS: Meta-analytic estimates suggest IIV is associated with subsequent cognitive decline and/or conversion to MCI/dementia (r = .20, 95% CI [.09, .31]) with no significant difference between the two operationalisations observed (Q = 3.41, p = .065). CONCLUSION: Cognitive IIV, including both IIV-I and IIV-D operationalizations, appears to be associated with subsequent cognitive decline and/or dementia and may offer a novel indicator of incipient dementia in both clinical and research settings. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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    Acute neuroimmune stimulation impairs verbal memory in adults: A PET brain imaging study
    Woodcock, EA ; Hillmer, AT ; Sandiego, CM ; Maruff, P ; Carson, RE ; Cosgrove, KP ; Pietrzak, RH (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2021-01-01)
    Psychiatric and neurologic disorders are often characterized by both neuroinflammation and cognitive dysfunction. To date, however, the relationship between neuroinflammation and cognitive dysfunction remains understudied in humans. Preclinical research indicates that experimental induction of neuroinflammation reliably impairs memory processes. In this paradigm development study, we translated those robust preclinical findings to humans using positron emission tomography (PET) imaging with [11C]PBR28, a marker of microglia, and lipopolysaccharide (LPS), a potent neuroimmune stimulus. In a sample of 18 healthy adults, we extended our previous findings that LPS administration increased whole-brain [11C]PBR28 availability by 31-50%, demonstrating a robust neuroimmune response (Cohen's ds > 1.6). We now show that LPS specifically impaired verbal learning and recall, hippocampal memory processes, by 11% and 22%, respectively (Cohen's ds > 0.9), but did not alter attention, motor, or executive processes. The LPS-induced increase in [11C]PBR28 binding was correlated with significantly greater decrements in verbal learning performance in the hippocampus (r = -0.52, p = .028), putamen (r = -0.50, p = .04), and thalamus (r = -0.55, p = .02). This experimental paradigm may be useful in investigating mechanistic relationships between neuroinflammatory signaling and cognitive dysfunction in psychiatric and neurologic disorders. It may also provide a direct approach to evaluate medications designed to rescue cognitive deficits associated with neuroinflammatory dysfunction.
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    A phase 1b/2a multicenter study of the safety and preliminary pharmacodynamic effects of selective muscarinic M1 receptor agonist HTL0018318 in patients with mild-to-moderate Alzheimer's disease.
    Nathan, PJ ; Millais, SB ; Godwood, A ; Dewit, O ; Cross, DM ; Liptrot, J ; Ruparelia, B ; Jones, SP ; Bakker, G ; Maruff, PT ; Light, GA ; Brown, AJH ; Weir, MP ; Congreve, M ; Tasker, T (Wiley, 2022)
    INTRODUCTION: This study examined the safety and pharmacodynamic effects of selective muscarinic M1 receptor orthosteric agonist HTL0018318 in 60 patients with mild-to-moderate Alzheimer's disease (AD) on background donepezil 10 mg/day. METHODS: A randomized, double-blind, placebo-controlled 4-week safety study of HTL0018318 with up-titration and maintenance phases, observing exploratory effects on electrophysiological biomarkers and cognition. RESULTS: Treatment-emergent adverse events (TEAEs) were mild and less frequently reported during maintenance versus titration. Headache was most commonly reported (7-21%); 0 to 13% reported cholinergic TEAEs (abdominal pain, diarrhea, fatigue, nausea) and two patients discontinued due to TEAEs. At 1 to 2 hours post-dose, HTL0018318-related mean maximum elevations in systolic and diastolic blood pressure of 5 to 10 mmHg above placebo were observed during up-titration but not maintenance. Postive effects of HTL0018318 were found on specific attention and memory endpoints. DISCUSSION: HTL0018318 was well tolerated in mild-to-moderate AD patients and showed positive effects on attention and episodic memory on top of therapeutic doses of donepezil.
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    Association of Neighborhood-Level Socioeconomic Measures With Cognition and Dementia Risk in Australian Adults.
    Pase, MP ; Rowsthorn, E ; Cavuoto, MG ; Lavale, A ; Yassi, N ; Maruff, P ; Buckley, RF ; Lim, YY (American Medical Association (AMA), 2022-03-01)
    Importance: Up to 40% of dementia cases are potentially preventable; therefore, it is important to identify high-risk groups to whom resources could be targeted for maximal impact in preventing late-life dementia. The association of neighborhood-level socioeconomic status (SES) with cognition and dementia risk is not well known, particularly in midlife when late-life dementia may still be preventable through established interventions, such as blood pressure management. Objective: To examine whether neighborhood-level SES is associated with differences in cognitive performance and dementia risk scores. Design, Setting, and Participants: This cross-sectional study analyzed data collected between November 17, 2016, and April 14, 2020, from 4656 participants in the longitudinal population-based Healthy Brain Project cohort. This large online cohort comprised community-dwelling individuals geographically dispersed across Australia. Participants were aged 40 to 70 years without dementia or other major neurological conditions. Exposures: Neighborhood-level SES was computed by matching participants' residential addresses to the Australian Bureau of Statistics Index of Relative Socio-economic Advantage and Disadvantage (IRSAD). Postcodes provided by each participant were used to derive an IRSAD score that ranked participants according to deciles of neighborhood-level SES (range, 1-10, with higher deciles indicating greater socioeconomic advantage); neighborhoods in deciles 1 to 7 were considered to have low or intermediate SES, and neighborhoods in deciles 8 to 10 were considered to have high SES. Main Outcomes and Measures: Dementia risk estimated using the dementia risk score from the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) tool (n = 4656) and cognitive composite scores for memory and attention measured by the Cogstate Brief Battery (n = 2181). Results: Of 4656 participants (mean [SD] age, 56.1 [7.2] years; 3445 women [74.0%]), 2688 individuals (57.7%) lived in areas with high neighborhood-level SES (IRSAD decile ≥8), and 1968 (42.3%) lived in areas with low or intermediate neighborhood-level SES (IRSAD decile <8), with 1263 individuals (27.1%) residing in rural or regional areas. A total of 6 participants (0.1%) identified as African, 121 (2.6%) as Asian, 57 (1.2%) as Indigenous Australian, 24 (0.5%) as Latin American, 9 (0.2%) as Pacific Islander, 3671 (78.8%) as White or European, and 768 (16.5%) indicated other race (not specified). Each decile unit increase in neighborhood-level SES was associated with a lower CAIDE dementia risk score after adjustment for race and rurality (β [SE] = -0.070 [0.019]; P = .004). Each decile unit increase was also associated with better memory (β [SE] = 0.022 [0.006]; P = .006) but not with better attention (β [SE] = 0.009 [0.007]; P = .34), as measured by Cogstate Brief Battery composite z scores after adjustment for age, sex, race, years of education, and rurality. When comparing memory performance between individuals with IRSAD scores higher and lower than decile 8, neighborhood-level SES interacted with age (F1-2171 = 6.33; P = .02) and CAIDE dementia risk scores (F1-2173 = 4.02; P = .08). Differences in memory between neighborhood-level SES categories were larger among participants who were older and had a higher risk of dementia. Conclusions and Relevance: In this study, higher neighborhood-level SES was associated with better memory and lower dementia risk scores. These results suggest that efforts to lower dementia risk factors in disadvantaged areas are needed to curtail the increasing burden of dementia and that inclusion of individuals living in areas with lower SES in research on dementia is warranted to improve understanding and potential interventions.
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    The relationship between cognitive engagement and better memory in midlife
    Bransby, L ; Buckley, RF ; Rosenich, E ; Franks, KH ; Yassi, N ; Maruff, P ; Pase, MP ; Lim, YY (WILEY, 2022-01-01)
    INTRODUCTION: Engagement in cognitively stimulating work and activities may slow cognitive decline and dementia. We examined the individual and combined associations of four cognitive engagement indices (educational attainment, occupational complexity, social engagement, and cognitively stimulating leisure activities) with objective and subjective cognition. METHODS: Middle-aged adults (n = 1864) enrolled in the Healthy Brain Project completed the Cogstate Brief Battery, the Cognitive Function Instrument, and self-report questionnaires of cognitive engagement. RESULTS: Educational attainment and leisure activity engagement were individually associated with memory performance. Participants were classified based on whether they rated highly in zero to four cognitive engagement indices. Compared to participants with no indices, participants with two or more indices performed moderately better on memory. DISCUSSION: Results suggest that greater variety of cognitive engagement across different areas of life is related to better memory in midlife. Possible explanation for this relationship may be increased opportunity for enhancing cognitive reserve, but further investigations are required.
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    Using health check data to investigate cognitive function in Aboriginal and Torres Strait Islanders living with diabetes in the Torres Strait, Australia
    Thompson, F ; Harriss, LR ; Russell, S ; Taylor, S ; Cysique, LA ; Strivens, E ; Maruff, P ; McDermott, R (WILEY, 2021-09-24)
    BACKGROUND: Type 2 Diabetes (T2DM) has a subtle deleterious effect on cognition and imposes a higher lifetime risk of cognitive impairment and dementia. In populations where both T2DM and dementia are highly prevalent, understanding more about the early effects of T2DM on cognition may provide insights into the lifetime risks of this disease. METHODS: In 2016, 186 Australian Aboriginal and/or Torres Strait Islander residents of the Torres Strait (54% female, mean age =38.9 years, SD =15.9, range =15-74) participated in a community health check. The effect of diabetes (Type 1 or Type 2) on speed of thinking and working memory was assessed with the Cogstate Brief Battery (CBB) during the health check. RESULTS: One third of participants had diabetes (n = 56, 30.1%). After adjusting for age, education and previous iPad/Tablet experience, participants with diabetes had a small, yet significant reduction in accuracy on the One Back working memory task (β = -.076, p = .010, r2  = .042). The effect was most pronounced among participants with diabetes aged 20-49 years (n = 20), who also had evidence of poorer diabetes control (eg HbA1c% ≥6.5, 76.6%), relative to participants with diabetes aged 50 years and over (n = 31) (HbA1c% ≥6.5, 32.0%, p = .005). CONCLUSIONS: Early and subtle decrements in working memory may be a potential complication of diabetes among Aboriginal and Torres Strait Islander residents of the Torres Strait. Several potentially influential variables were not captured in this study (eg medication and diabetes duration). Greater preventative health resources are required for this population, particularly given the emerging elevated dementia rates linked to chronic disease.
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    Gender moderates the association between chronic academic stress with top-down and bottom-up attention
    Wright, BJ ; Wilson, K-E ; Kingsley, M ; Maruff, P ; Li, J ; Siegrist, J ; Ben, H (SPRINGER, 2022-02-17)
    Research on the relationship between chronic stress and cognition is limited by a lack of concurrent measurement of state-anxiety, physiological arousal, and gender. For the first time, we assessed the impact of these factors on top-down/conscious (simple and choice reaction time) and bottom-up/reflexive (saccadic reaction time) measures of attention using CONVIRT virtual-reality cognitive tests. Participants (N = 163) completed measures of academic stress (effort-reward imbalance; ERI) and state-anxiety while heart-rate variability was recorded continuously throughout the experiment. Gender moderated the association between academic stress with the top-down measures (b = -0.002, t = -2.023, p = .045; b = -0.063, t = -3.080, p = .002) and higher academic stress was associated with poorer/slower reaction times only for male participants. For bottom-up attention, heart rate variability moderated the relationship between academic stress and saccadic reaction time (b = 0.092, t = 1.991, p = .048), and only female participants who were more stressed (i.e., ERI ≥ 1) and displayed stronger sympathetic dominance had slower reaction times. Our findings align with emerging evidence that chronic stress is related to hyperarousal in women and cognitive decrements in men. Our findings suggest that higher ERI and sympathetic dominance during cognitive testing was associated with poorer bottom-up attention in women, whereas for men, academic stress was related with poorer top-down attention irrespective of sympathovagal balance.