Psychiatry - Research Publications

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    A Randomized Controlled Trial on the Effects of a 6-Month Home-Based Physical Activity Program with Individual Goal-Setting and Volunteer Mentors on Physical Activity, Adherence, and Physical Fitness in Inactive Older Adults at Risk of Cognitive Decline: The INDIGO Study
    Cox, KL ; Clare, L ; Cyarto, E ; Ellis, KA ; Etherton-Beer, C ; Southam, J ; Ames, D ; Flicker, L ; Almeida, OP ; LoGiudice, D ; Liew, D ; Vlaskovsky, P ; Lautenschlager, NT ; Hauer, K (IOS PRESS, 2021-01-01)
    BACKGROUND: Increasing physical activity (PA) in those who have memory concerns requires innovative approaches. OBJECTIVE: To compare in this randomized controlled trial (RCT) the effects on PA, adherence, and fitness of two approaches to deliver a 6-month home-based PA program in older, inactive individuals at risk of cognitive decline. METHODS: Individuals (n = 52) aged 60-85 years, inactive with mild cognitive impairment or subjective cognitive decline were recruited from the community and memory clinics. Randomization was to 6 months of 150 min/week moderate intensity PA with either: goal-setting with mentor support; or education and peer contact. A subset of participants (n = 36) continued for a further 6 months. PA, moderate and vigorous PA, and secondary outcomes, fitness, goal performance/satisfaction and self-efficacy were assessed at baseline, 6 and 12 months. Modelling of primary and secondary outcomes was conducted with linear mixed models. RESULTS: Participants were mean age (±sd) 70.1 (6.4) years. Six-month retention was 88.5%(n = 46). No significant between-group differences were observed for PA or fitness. Post-hoc combined group data showed a significant, moderate-large effect size increase in PA with time. PA increased by a mean 1,662 (943, 2383) steps/day (95%CI) and 1,320 (603, 2037) steps/day at 6 and 12 months (p < 0.001). Median (quartiles Q1-Q3) 6 and 6-12 month combined group adherence was 88.9 (74.4-95.7)%and 84.6 (73.9-95.4)%respectively. CONCLUSION: In this target group, no differences were detected between groups both intervention strategies were highly effective in increasing PA and fitness.
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    Non-negative matrix factorisation improves Centiloid robustness in longitudinal studies
    Bourgeat, P ; Dore, V ; Doecke, J ; Ames, D ; Masters, CL ; Rowe, CC ; Fripp, J ; Villemagne, VL (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2021-02-01)
    BACKGROUND: Centiloid was introduced to harmonise β-Amyloid (Aβ) PET quantification across different tracers, scanners and analysis techniques. Unfortunately, Centiloid still suffers from some quantification disparities in longitudinal analysis when normalising data from different tracers or scanners. In this work, we aim to reduce this variability using a different analysis technique applied to the existing calibration data. METHOD: All PET images from the Centiloid calibration dataset, along with 3762 PET images from the AIBL study were analysed using the recommended SPM pipeline. The PET images were SUVR normalised using the whole cerebellum. All SUVR normalised PiB images from the calibration dataset were decomposed using non-negative matrix factorisation (NMF). The NMF coefficients related to the first component were strongly correlated with global SUVR and were subsequently used as a surrogate for Aβ retention. For each tracer of the calibration dataset, the components of the NMF were computed in a way such that the coefficients of the first component would match those of the corresponding PiB. Given the strong correlations between the SUVR and the NMF coefficients on the calibration dataset, all PET images from AIBL were subsequently decomposed using the computed NMF, and their coefficients transformed into Centiloids. RESULTS: Using the AIBL data, the correlation between the standard Centiloid and the novel NMF-based Centiloid was high in each tracer. The NMF-based Centiloids showed a reduction of outliers, and improved longitudinal consistency. Furthermore, it removed the effects of switching tracers from the longitudinal variance of the Centiloid measure, when assessed using a linear mixed effects model. CONCLUSION: We here propose a novel image driven method to perform the Centiloid quantification. The methods is highly correlated with standard Centiloids while improving the longitudinal reliability when switching tracers. Implementation of this method across multiple studies may lend to more robust and comparable data for future research.
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    Assessment of the DTI-ALPS Parameter Along the Perivascular Space in Older Adults at Risk of Dementia
    Steward, CE ; Venkatraman, VK ; Lui, E ; Malpas, CB ; Ellis, KA ; Cyarto, EV ; Vivash, L ; O'Brien, TJ ; Velakoulis, D ; Ames, D ; Masters, CL ; Lautenschlager, NT ; Bammer, R ; Desmond, PM (WILEY, 2021-02-08)
    BACKGROUND AND PURPOSE: Recently, there has been growing interest in the glymphatic system (the functional waste clearance pathway for the central nervous system and its role in flushing solutes (such as amyloid ß and tau), metabolic, and other cellular waste products in the brain. Herein, we investigate a recent potential biomarker for glymphatic activity (the diffusion tensor imaging along the perivascular space [DTI-ALPS] parameter) using diffusion MRI imaging in an elderly cohort comprising 10 cognitively normal, 10 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD). METHODS: All 36 participants imaged on a Siemens 3.0T Tim Trio. Single-SE diffusion weighted Echo-planar imaging scans were acquired as well as T1 magnetization prepared rapid gradient echo, T2 axial, and susceptibility weighted imaging. Three millimeter regions of interest were drawn in the projection and association fibers adjacent to the medullary veins at the level of the lateral ventricle. The DTI-ALPS parameter was calculated in these regions and correlated with cognitive status, Mini-Mental State Examination (MMSE), and ADASCog11 measures. RESULTS: Significant correlations were found between DTI-ALPS and MMSE and ADASCog11 in the right hemisphere adjusting for age, sex, and APoE ε4 status. Significant differences were also found in the right DTI-ALPS indices between cognitively normal and AD groups (P < .026) and MCI groups (P < .025) in a univariate general linear model corrected for age, sex, and APoE ε4. Significant differences in apparent diffusion coefficient between cognitively normal and AD groups were found in the right projection fibers (P = .028). CONCLUSION: Further work is needed to determine the utility of DTI-ALPS index in larger elderly cohorts and whether it measures glymphatic activity.
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    Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group
    Jia, T ; Chu, C ; Liu, Y ; van Dongen, J ; Papastergios, E ; Armstrong, NJ ; Bastin, ME ; Carrillo-Roa, T ; den Braber, A ; Harris, M ; Jansen, R ; Liu, J ; Luciano, M ; Ori, APS ; Santianez, RR ; Ruggeri, B ; Sarkisyan, D ; Shin, J ; Sungeun, K ; Gutierrez, DT ; van't Ent, D ; Ames, D ; Artiges, E ; Bakalkin, G ; Banaschewski, T ; Bokde, ALW ; Brodaty, H ; Bromberg, U ; Brouwer, R ; Buchel, C ; Quinlan, EB ; Cahn, W ; de Zubicaray, G ; Ehrlich, S ; Ekstrom, TJ ; Flor, H ; Frohner, JH ; Frouin, V ; Garavan, H ; Gowland, P ; Heinz, A ; Hoare, J ; Ittermann, B ; Jahanshad, N ; Jiang, J ; Kwok, JB ; Martin, NG ; Martinot, J-L ; Mather, KA ; McMahon, KL ; McRae, AF ; Nees, F ; Orfanos, DP ; Paus, T ; Poustka, L ; Samann, PG ; Schofield, PR ; Smolka, MN ; Stein, DJ ; Strike, LT ; Teeuw, J ; Thalamuthu, A ; Trollor, J ; Walter, H ; Wardlaw, JM ; Wen, W ; Whelan, R ; Apostolova, LG ; Binder, EB ; Boomsma, D ; Calhoun, V ; Crespo-Facorro, B ; Deary, IJ ; Pol, HH ; Ophoff, RA ; Pausova, Z ; Sachdev, PS ; Saykin, A ; Wright, MJ ; Thompson, PM ; Schumann, G ; Desrivieres, S (SPRINGERNATURE, 2021-08-01)
    DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
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    The Support Person's Preferences and Perspectives of Physical Activity Programs for Older Adults With Cognitive Impairment
    Chong, TWH ; You, E ; Ellis, KA ; Cox, KL ; Harrington, KD ; Rainey-Smith, SR ; Ames, D ; Lautenschlager, NT (FRONTIERS MEDIA SA, 2021-09-23)
    Objectives: Physical activity (PA) is beneficial for older adults' cognition. There is limited research investigating perspectives of support persons (SPs) of next-of-kins (NOKs) with cognitive impairment. This exploratory study aimed to investigate perspectives of SPs of older adults with Alzheimer's Dementia (AD) or Mild Cognitive Impairment (MCI). Methods: A telephone survey of 213 SPs of NOKs from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) was undertaken to quantitatively assess SPs' beliefs and knowledge about PA benefits, current PA level of their NOK, and PA program preferences. The contribution of age, gender, diagnosis and mental health symptoms was assessed using multiple logistic regression analyses. Results: Many SPs were aware of PA benefits for memory (64%) and believed it would help their NOK (72%). Older SP age was associated with less awareness of benefits (p = 0.016). SPs caring for male NOKs were more likely to believe that PA would be helpful than those caring for female NOKs (p = 0.049). NOK AD diagnosis (rather than MCI) (p = 0.014), older age (p = 0.005) and female gender (p = 0.043) were associated with lower PA levels. SPs were mixed regarding preference for their NOKs to participate in individual (45%) or group (54%) PA. Many SPs wanted to participate in PA with their NOK (63%). Conclusions: The results highlight that SPs have high levels of awareness of the cognitive benefits of PA, and describe their preferences regarding PA programs. The findings provide new information to inform targeted public health messaging, PA prescribers and providers, and future research directions.
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    Promoting Independence Through quality dementia Care at Home (PITCH): a research protocol for a stepped-wedge cluster-randomised controlled trial
    Savvas, S ; Goh, AMY ; Batchelor, F ; Doyle, C ; Wise, E ; Tan, E ; Panayiotou, A ; Malta, S ; Winbolt, M ; Clarke, P ; Burton, J ; Low, L-F ; Loi, SM ; Fairhall, A ; Polacsek, M ; Stiles, J ; Muliadi, F ; Chau, N ; Scherer, S ; Ames, D ; Sousa, TV ; Dow, B (BMC, 2021-12-20)
    BACKGROUND: Home care service providers are increasingly supporting clients living with dementia. Targeted and comprehensive dementia-specific training for home care staff is necessary to meet this need. This study evaluates a training programme delivered to care staff (paid personal carers) of clients living with dementia at home. METHODS: This study is a pragmatic stepped-wedge cluster-randomised controlled trial (SW-CRT). Home care workers (HCWs) from seven home care service providers are grouped into 18 geographical clusters. Clusters are randomly assigned to intervention or control groups. The intervention group receives 7 h of a dementia education and upskilling programme (Promoting Independence Through quality dementia Care at Home [PITCH]) after baseline measures. The control group receives PITCH training 6 months after baseline measures. This approach will ensure that all participants are offered the program. Home care clients living with dementia are also invited to participate, as well as their family carers. The primary outcome measure is HCWs' sense of competence in dementia care provision. DISCUSSION: Upskilling home care staff is needed to support the increasing numbers of people living with dementia who choose to remain at home. This study uses a stepped-wedge cluster-randomised trial to evaluate a training programme (PITCH) for dementia care that is delivered to front-line HCWs. TRIAL REGISTRATION: anzctr.org.au ; ACTRN12619000251123. Registered on 20 February 2019.
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    Spousal recollections of early signs of primary progressive aphasia
    Pozzebon, M ; Douglas, J ; Ames, D (WILEY, 2018-03-01)
    BACKGROUND: Although primary progressive aphasia (PPA) is characterized by progressive loss of language and communication skills, knowledge about the earliest emerging signs announcing the onset of this condition is limited. AIMS: To explore spousal recollections regarding the earliest signs of PPA and to compare the nature of the earliest perceived symptoms across the three PPA variants. METHODS & PROCEDURES: In-depth interviews focusing on the earliest signs of illness onset were conducted with 13 spouses whose partners were diagnosed with PPA. The earliest recollections and observations described by the spouses were analyzed and coded according to the DSM-5 criteria for a mild neurocognitive disorder. These data were then compared across and within each of the three PPA variants. OUTCOMES & RESULTS: Spousal retrospective accounts indicated the three PPA variants (semantic, logopenic and non-fluent) had a signature profile announcing illness onset. Changes in social cognition presented in all three variants of PPA, but at different points in the illness trajectory. In particular, the findings suggest the possibility that PPA initially presents as subtle changes in social cognition for semantic variant PPA (svPPA) and logopenic variant PPA (IvPPA) rather than overt language impairments as defined in the current diagnostic criteria. CONCLUSIONS & IMPLICATIONS: Understanding the nature of symptoms perceived in the earliest stages of PPA has potential to inform earlier and accurate diagnosis and interventions to assist those living with the illness.
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    Trajectories of depressive and anxiety symptoms in older adults: a 6-year prospective cohort study
    Holmes, SE ; Esterlis, I ; Mazure, CM ; Lim, YY ; Ames, D ; Rainey-Smith, S ; Fowler, C ; Ellis, K ; Martins, RN ; Salvado, O ; Dore, V ; Villemagne, VL ; Rowe, CC ; Laws, SM ; Masters, CL ; Pietrzak, RH ; Maruff, P (WILEY, 2018-02-01)
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    The impact of telephone-delivered cognitive behaviour therapy and befriending on mood disorders in people with chronic obstructive pulmonary disease: A randomized controlled trial
    Doyle, C ; Bhar, S ; Fearn, M ; Ames, D ; Osborne, D ; You, E ; Gorelik, A ; Dunt, D (WILEY, 2017-09-01)
    OBJECTIVES: The main objectives of this pragmatic randomized controlled trial were to investigate the impact of cognitive behaviour therapy (CBT) and an active social control (befriending) on depression and anxiety symptoms in people with chronic obstructive pulmonary disease (COPD). METHODS: Eligible participants were randomly allocated to receive eight weekly telephone interventions of CBT (n = 54) or befriending (n = 56). Repeated-measures ANOVA was used to assess changes in scores and Cohen's d was used to assess effect sizes. RESULTS: Significant improvement was observed in anxiety symptoms for the befriending group from baseline (T1) to post-intervention assessment (T2) and to 8-week follow-up assessment (T3), with a small to medium effect size (Cohen's d = 0.3). Significant improvement was noted in depression symptoms from T1 to T2 for both groups, but only the CBT group had a significant difference at T3, with a small to medium effect size (Cohen's d = 0.4). For secondary outcomes, there was a significant change in COPD symptoms from T1 to T2 for the befriending group; however, at T3 this change was no longer significant. Finally, there was a significant change in general self-efficacy for both groups between T1 and T2, and T1 and T3. CONCLUSION: Cognitive behaviour therapy reduced depression symptoms but not anxiety. Befriending reduced depression symptoms in the short term and anxiety symptoms in both the short term and long term. Further research is needed to demonstrate non-inferiority of telephone delivery compared with other formats, and to understand the impact of befriending which has the potential to be a cost-effective support for people with COPD. Statement of contribution What is already known on this subject? Depression and anxiety are common comorbidities in people with chronic obstructive pulmonary disease. Mood disorders are not commonly routinely treated in people with chronic obstructive pulmonary disease. Telephone-administered CBT has been shown to be as effective as face-to-face CBT in reducing depression and anxiety. What does this study add? Telephone-administered CBT can reduce depression symptoms in people with COPD. Telephone-administered befriending can reduce anxiety and depression symptoms in people with COPD. People with COPD who have mood disorders would prefer to have CBT than befriending.
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    The interactive effect of demographic and clinical factors on hippocampal volume: A multicohort study on 1958 cognitively normal individuals
    Ferreira, D ; Hansson, O ; Barroso, J ; Molina, Y ; Machado, A ; Andres Hernandez-Cabrera, J ; Muehlboeck, J-S ; Stomrud, E ; Nagga, K ; Lindberg, O ; Ames, D ; Kalpouzos, G ; Fratiglioni, L ; Backman, L ; Graff, C ; Mecocci, P ; Vellas, B ; Tsolaki, M ; Kloszewska, I ; Soininen, H ; Lovestone, S ; Ahlstrom, H ; Lind, L ; Larsson, E-M ; Wahlund, L-O ; Simmons, A ; Westman, E (WILEY, 2017-06-01)
    Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.