Psychiatry - Research Publications
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ItemThe Early Mid-Career Committee (EMCC) of the International Society for Bipolar Disorders: Aspirations and goals(Wiley, 2022-12)In 2021, the International Society for Bipolar Disorders (ISBD) launched a new global initiative to support researchers and clinicians specializing in bipolar disorder who are still in the process of establishing their careers. To capture the needs of this group, an Early and Mid-Career Committee (EMCC) was formed and tasked with the development of activities and initiatives to address this objective. To this end, the committee conducted a needs assessment survey in early 2022 that was distributed and completed worldwide. This paper, authored by members of the committee, outlines the rationale, process, goals, and aspirations of the EMCC and summarizes the development of the needs survey.
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ItemNo Preview AvailableDevelopment of harmonized and co‐calibrated scores for memory, executive functioning, language, and visuospatial in the AIBL Study, ADNI, and NACC datasets(Wiley, 2022-12)Background The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study is a prospective study collecting extensive cognitive, clinical, fluid, and imaging biomarkers data from older adults living in Australia. Integration of outcomes between large prospective studies of AD will provide greater precision in models of AD brain‐behavior relationships, so it is important to align composite scores for cognitive domains between such studies. Methods Detailed methods for AIBL, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the National Alzheimer’s Coordinating Center (NACC) have been published. Briefly, AIBL participants had cognition assessed with an extensive neuropsychological test battery alongside health and biomarker assessments at entry and each 18‐months thereafter. Granular‐level cognitive data were obtained and an expert panel of two neuropsychologists and a behavioral neurologist categorized each element as assessing memory, executive functioning, language, visuospatial, or none of these, exactly as we have done previously. We also identified elements we had previously calibrated from other studies; after careful quality control and confirmation these served as anchors enabling co‐calibration. We used confirmatory factor analysis bi‐factor models to calibrate the AIBL battery with other studies. We used those calibrations to obtain co‐calibrated scores for all AIBL participants at every study visit. Here we show descriptive statistics for baseline visits, separately by diagnosis (normal cognition, mild cognitive impairment (MCI), dementia) for two enrollment waves for AIBL as well as for each phase of ADNI and across the Uniform Data Set (UDS) 1 & 2 (UDS1/2) and UDS3 time periods for NACC. Results Box plots for memory, executive functioning, language, and visuospatial for people with normal cognition are in Figure 1, MCI in Figure 2, and dementia in Figure 3. These figures show there is substantial cognitive variation across waves within these disease stage groups and across studies. Conclusion Co‐calibrated neuropsychological domain scores provide a common metric for integrating cognitive data across studies. Co‐calibrated scores aggregated across large prospective AD studies such as AIBL, ADNI, and NACC provide a foundation for large‐scale models of the development of AD and can serve as phenotypes for genetics studies. Co‐calibrated scores are available from AIBL, ADNI, and from NACC.
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ItemNo Preview AvailableCerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from ‘phenocopy’ non‐progressors(Wiley, 2022-12)Background Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non‐neurodegenerative ‘non‐progressor’, ‘phenocopy’ mimics of frontal lobe dysfunction, can be one of the most challenging clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL), could reduce misdiagnosis and delay. Method Cerebrospinal fluid (CSF) NfL, amyloid beta 1‐42 (AB42), total and phosphorylated tau (T‐tau, P‐tau) levels were examined in patients with an initial diagnosis of bvFTD. Based on follow up information, patients were categorised as Progressors. Non‐Progressors were subtyped in to Phenocopy Non‐Progressors (non‐neurological/neurodegenerative final diagnosis), and Static Non‐Progressors (static deficits, not fully explained by non‐neurological/neurodegenerative causes). Result Forty‐three patients were included: 20 Progressors, 23 Non‐Progressors (15 Phenocopy, 8 Static), 20 controls. NfL concentrations were lower in Non‐Progressors (Non‐Progressors Mean, M=554pg/mL, 95%CI:[461, 675], Phenocopy Non‐Progressors M=459pg/mL, 95%CI:[385, 539], Static Non‐Progressors M=730pg/mL, 95%CI:[516, 940]), compared to bvFTD Progressors (M=2397pg/mL, 95%CI:[1607, 3332]). NfL distinguished Progressors from Non‐Progressors with the highest accuracy (area under the curve 0.92, 90%/87% sensitivity/specificity, 86%/91% positive/negative predictive value, 88% accuracy). Static Non‐Progressors tended to have higher T‐tau and P‐tau levels compared to Phenocopy Non‐Progressors. Conclusion This study demonstrated strong diagnostic utility of CSF NfL in distinguishing bvFTD from phenocopy non‐progressor variants, at baseline, with high accuracy, in a real‐world clinical setting. This has important clinical implications to improve outcomes for patients and clinicians facing this challenging clinical dilemma, as well as for healthcare services, and clinical trials. Further research is required to investigate heterogeneity within the non‐progressor group and potential diagnostic algorithms, and prospective studies are underway assessing plasma NfL.
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ItemNo Preview AvailableMaintain Your Brain: a 3‐year online randomized controlled trial to reduce cognitive decline in 55‐77 year olds(Wiley, 2022-12)Background Technology and web‐based approaches potentially provide scalable population‐based interventions to reduce modifiable risk factors for dementia such as physical inactivity, suboptimal nutrition and low cognitive activity. Our aim was to reduce cognitive decline with ageing using an online package of interventions delivered intensively for 12 months followed by monthly boosters for 24 months. The trial was completed in November 2021. Method Invitations were sent to people aged 55‐77 years from the 45 and Up study, a population‐based cohort study of one in ten people aged 45 years and older in New South Wales, Australia (n = 267,000). Participants were required to be eligible for at least two of four modules. The modules addressed physical inactivity and health risks associated with inactivity (Physical Activity), adherence to a Mediterranean‐type diet and health risks associated with poor nutrition (Nutrition), cognitive activity (Brain Training) and mental well‐being (Peace of Mind). All participants received modules based on their risks, with randomized allocation to active personalised coaching modules (intervention) or static information‐based modules (control). The primary outcome was change in an online combined multi‐domain cognitive score measured using COGSTATE and Cambridge Brain Sciences tests. Secondary outcomes included ANU‐ADRI risk score, specific cognitive domain scores and diagnoses of dementia. Result From 96,418 invitations, 14,064 (14%) consented; 12,281 (13%) were eligible. Of these, 6,236 (6%) completed all 10 baseline assessments and were enrolled in the trial. Nearly 70% or 4,365 participants provided follow‐up data. At final 36‐months’ follow‐up, 3,482 (55.8%) completed the primary outcome and 2594 (41.6%) had returned informant‐rated Amsterdam‐Instrumental Activities of Daily Living Scale questionnaires. Conclusion Online strategies to prevent cognitive decline in 55‐77 year olds are feasible and appear acceptable for more than half of participants. Analysis of group*time effects will be presented.
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ItemNo Preview AvailableObjectively measured physical activity and cognition in cognitively normal older adults: A longitudinal analysis of the Australian Imaging Biomarkers and Lifestyle (AIBL) study(Wiley Open Access, 2022-12)Background Physical inactivity is one of the greatest modifiable risk factors for dementia and research shows physical activity can delay cognitive decline in older adults. However, much of this research has used subjective physical activity data and a single follow‐up cognitive assessment. Further studies using objectively measured physical activity and comprehensive cognitive data measured at multiple timepoints are required. Methods Participants were 199 community‐dwelling cognitively normal older adults (68.7 5.9 years) from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Actigraphy was used to measure physical activity at baseline, yielding measures of intensity (peak counts), total activity (total counts) and energy expenditure (kilocalories; k/cal). Cognitive function was assessed using a cognitive battery administered every 18‐months from baseline (3‐11 years follow‐up), yielding composite scores for episodic memory, executive function, attention and processing speed, and global cognition. Results Higher baseline energy expenditure predicted improvements in episodic memory and maintained global cognition over time (β = 0.011, SE = 0.005, p = 0.031; β = 0.009, SE = 0.004, p = 0.047, respectively). Both physical activity intensity and total activity predicted global cognition, such that those with higher peak and total counts had better cognition over time (β = 0.012, SE = 0.004, p = 0.005; β = 0.012, SE = 0.004, p = 0.005, respectively). Finally, higher total activity predicted improved episodic memory over time (β = 0.011, SE = 0.005, p = .022). Conclusion These results suggest that physical activity is associated with preserved cognitive function over time, and that activity intensity may play an important role. This research further highlights the importance of early intervention to prevent cognitive decline and may aid in informing lifestyle interventions for dementia prevention.
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ItemNo Preview AvailablePlasma glial fibrillary acidic protein is associated with reactive astrogliosis assessed via 18F-SMBT-1 PET(Wiley, 2022-12)Background Reactive astrogliosis is an early event along the Alzheimer’s disease (AD) continuum. We have shown that plasma glial fibrillary acidic protein (GFAP), reflecting reactive astrogliosis, is elevated in cognitively unimpaired individuals with preclinical AD (Chatterjee et al., 2021). We reported similar findings using 18F‐SMBT‐1, a PET tracer for monoamine oxidase B (MAO‐B) (Villemagne et al., 2022). To provide further evidence of their relationship with reactive astrogliosis we investigated the association between GFAP and 18F‐SMBT‐1 in the same participants. Method Plasma GFAP, Aβ42 and Aβ40 levels were measured using the Single Molecule Array platform in 71 participants comprising 54 healthy controls (12 Aβ+ and 42 Aβ‐), 11 MCI(3 Aβ+ and 8 Aβ‐) and 6 probable AD(5 Aβ+ and 1 Aβ‐) patients from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing cohort. These participants also underwent 18F‐SMBT‐1 and Aβ PET imaging. Aβ imaging results were expressed in Centiloids (CL; ≥20 CL classified as Aβ+). 18F‐SMBT‐1 Standard Uptake Value Ratio (SUVR) were generated using the subcortical white matter as reference region. Linear regression analyses were carried out using plasma GFAP levels as the dependent variable and regional 18F‐SMBT‐1 SUVR as the independent variable, before and after adjusting for age, sex, soluble Aβ (plasma Aβ1‐42/Aβ1‐40 ratio) and insoluble Aβ (Aβ PET). Result Plasma GFAP was significantly associated with 18F‐SMBT‐1 SUVR in brain regions of early Aβ deposition, such as the supramarginal gyrus (SG, β=.361, p=.002), posterior cingulate (PC, β=.308, p=.009), lateral temporal (LT, β=.299, p=.011), lateral occipital (LO, β=.313, p=.008) before adjusting for any covariates. After adjusting for covariates age, sex and soluble Aβ, GFAP was significantly associated with 18F‐SMBT‐1 PET signal in the SG (β=.333, p<.001), PC (β=.278, p=.005), LT (β=.256, p=.009), LO (β=.296, p=.004) and superior parietal (SP, β=.243, p=.016). On adjusting for age, sex and insoluble Aβ, GFAP was significantly associated with SMBT‐1 PET in the SG (β=.211, p=.037) however only a trend towards significance was observed in the PC (β=.186, p=.052) and LT (β=.171, p=.067) (Figure 1). Conclusion There is an association between plasma GFAP and regional SMBT‐1 PET that is primarily driven by brain Aβ load.
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ItemEarly interventions for youth at high risk for bipolar disorder(WILEY, 2022-12)
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ItemNo Preview AvailableThe effect of sad mood on subjective appraisal of memory performance in older people with and without subjective memory complaints: An experimental study(Wiley, 2021-12)Background Subjective memory complaints (SMC) have been identified as a possible precursor to cognitive decline and may indicate a need for an early intervention for at‐risk older adults. However, it is well‐established that low mood is associated with SMC, leading to claims that memory concerns in older people may often reflect primarily psychological symptoms. This study aimed to determine the effect of low mood on subjective memory appraisal in older adults. Method We used a film‐based mood induction procedure (MIP) to test the effect of sad vs. neutral mood on subjective appraisal of memory performance in an experimental 2X2 between‐subjects design. Participants were 98 cognitively unimpaired older people (n=45 with SMC), randomised to the sad MIP (n=56) or the neutral MIP (n=42). All participants completed measures of trait SMC and ruminative self‐focused attention (RSFA) as well as perceived performance and metacognitive experience (ME) following the MIP and completion of a face‐name and a maze‐learning task. Result Participants in the sad MIP condition (M=42.75, SD=30.97) reported significantly greater sadness than those in the neutral condition following the manipulation (M=11.57, SD=18.44). The association between objective and subjective memory performance was stronger for cued recall on the face‐name task (r=.61, p=.001) and was weaker free recall on the face‐name task (r=.26, p=0.016) as well on the maze‐learning task (r=‐.16, p=.200). Contrary to expectation, there was no significant effect of mood condition on perceived performance on Face‐Name learning task (MD=‐2.43, p=498), but sad mood was associated with better perceived performance on the maze‐learning task (MD=13.34, p=.015). Results also indicated that RSFA and ME were implicated as mechanisms in subjective memory performance appraisal. Conclusion Findings indicate that SMC is a complex multifaceted phenomenon which may be underpinned by maladaptive self‐regulation and attentional systems, suggesting that psychological interventions may be appropriate for many older adults with SMC.
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ItemNo Preview AvailableThe Mediterranean diet and physical activity: A cross-sectional analysis of the Maintain Your Brain randomised controlled trial(Wiley, 2021-12-01)BACKGROUND: Dementia has no pharmacological cure. Therefore, lifestyle interventions targeting modifiable risk factors to reduce cognitive decline are of interest. This study examines the cross-sectional relationships between two potentially protective behaviours: Mediterranean diet (MediDiet) adherence and physical activity (PA). METHOD: Participants were recruited from the Sax Institute's 45 and Up Study into the Maintain Your Brain trial. MediDiet adherence was assessed using the validated Mediterranean Diet and Culinary Index (MediCul) tool. The 50-item tool consists of 17 sub-categories focusing on key aspects of the MediDiet. Leisure time PA was assessed by a standard questionnaire and intensity was quantified using the BORG Rating of Perceived Exertion (RPE) scale, modified for strength and aerobic activities. Associations between the MediDiet and PA were investigated using hierarchical linear regression and analysis of covariance. RESULT: 6236 participants [55-77 years; mean (SD)=65.0 (5.8)] completed baseline assessments and were included. Mean (SD) MediCul score was 53.2 (13.0)/100), indicating low adherence to the MediDiet. Only 5% of participants achieved a score consistent with better cognitive outcomes in The PREDIMED study. Almost one-half of participants (48.4%) met aerobic PA (150 min/week) but less than one-quarter (24.2%) met resistance training (RT) recommendations (2 days/week). Unadjusted MediCul score explained a small but significant amount of the variance for light (1.0%) and moderate-vigorous (MV) (3.1%) PA, both p<0.001. For light PA, the final model, including MediCul, age, sex, BMI, CAGE (alcohol use) score and diabetes explained 2.8% of the variance. For MV PA, the final model including MediCul, age, sex, BMI, CAGE, depression, diabetes and education explained 10.9% of the variance. A 10-point higher MediCul score was associated with an additional 3.3 seconds of light PA/wk and additional 7.5 seconds of MV aerobic PA/wk (both p<0.001). Additionally, MediCul score was significantly higher in participants engaging in 2+days/wk of RT compared to 1 or fewer days/wk (56.6/100 vs. 52.2/100, respectively; p<0.001). CONCLUSION: Both aerobic and RT PA are significantly but weakly associated with better diet, but the clinical meaningfulness, as well as any causal nature, of these relationships requires further exploration. The outcomes of the MYB trial will contribute substantively to this question.