Psychiatry - Research Publications
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ItemNo Preview AvailableManaging mood disorders in patients attending pulmonary rehabilitation clinics(DOVE MEDICAL PRESS LTD, 2013)BACKGROUND: There is good evidence for the positive benefits of pulmonary rehabilitation (PR) in the prevention of hospital admissions, lower mortality, and improved health-related quality of life. There is also increasing evidence about the impact of PR on mental health and, in particular, mood disorders. We aimed to identify how depression in chronic obstructive pulmonary disease (COPD) patients in Victoria, Australia, is being managed in PR, to identify the prevalence of depressive symptoms among COPD patients who attend PR, and to determine whether patients with depressive symptoms or anxiety symptoms dropped out of PR early. METHOD: Of 61 PR clinics, 44 were invited and 22 agreed to participate. Telephone interviews were conducted to see how depression and anxiety in COPD patients were being recognized and managed in these clinics. A total of 294 questionnaires were distributed to patients by clinic coordinators to determine the prevalence of anxiety/depression, as measured by the Hospital Anxiety and Depression Scale. Coordinators were contacted to provide information on whether respondents dropped out of rehabilitation early or continued with their treatment at 2-4 months post program. RESULTS: Seven clinics were not aware of local guidelines on assessment/treatment/management of mood. Four clinics did not use any screening tools or other aids in the recognition and management of depression and/or anxiety. Overall, eight clinics participating in this study requested advice on suitable screening tools. The patient survey indicated that the mean depression score on the Hospital Anxiety and Depression Scale was 5.0 (standard deviation 3.0, range 1-13). The mean anxiety score was 5.5 (standard deviation 3.4, range 0-18). There was no evidence of a link between failure to complete rehabilitation and depression or anxiety scores, as only three of 105 patients failed to complete their rehabilitation. DISCUSSION: Awareness of management guidelines for depression and anxiety in COPD patients was variable across the clinics recruited into our study. We found no link between compliance with rehabilitation and depression, but our sample had limitations. CONCLUSION: Future research needs to investigate how best to encourage more use of available guidelines regarding integrating psychological and psychosocial support to supplement the exercise and education that are currently offered routinely by all PR clinics studied in Victoria, Australia.
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ItemThe fitness for the Ageing Brain Study II (FABS II): protocol for a randomized controlled clinical trial evaluating the effect of physical activity on cognitive function in patients with Alzheimer's disease(BMC, 2010-12-10)BACKGROUND: Observational studies have documented a potential protective effect of physical exercise in older adults who are at risk for developing Alzheimer's disease. The Fitness for the Ageing Brain II (FABS II) study is a multicentre randomized controlled clinical trial (RCT) aiming to determine whether physical activity reduces the rate of cognitive decline among individuals with Alzheimer's disease. This paper describes the background, objectives of the study, and an overview of the protocol including design, organization and data collection methods. METHODS/DESIGN: The study will recruit 230 community-dwelling participants diagnosed with Alzheimer's disease. Participants will be randomly allocated to two treatment groups: usual care group or 24-week home-based program consisting of 150 minutes per week of tailored moderate physical activity. The primary outcome measure of the study is cognitive decline as measured by the change from baseline in the total score on the Alzheimer's disease Assessment Scale-Cognitive section. Secondary outcomes of interest include behavioral and psychological symptoms, quality of life, functional level, carer burden and physical function (strength, balance, endurance, physical activity). Primary endpoints will be measured at six and twelve months following the baseline assessment. DISCUSSION: This RCT will contribute evidence regarding the potential benefits of a systematic program of physical activity as an affordable and safe intervention for people with Alzheimer's disease. Further, if successful, physical activity in combination with usual care has the potential to alleviate the symptoms of Alzheimer's disease and improve its management and the quality of life of patients and their carers. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12609000755235.
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ItemAssociation of Plasma Aβ Peptides with Blood Pressure in the Elderly(PUBLIC LIBRARY SCIENCE, 2011-04-15)BACKGROUND: Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). METHODOLOGY/PRINCIPAL FINDINGS: Plasma Aß(1-40) and Aß(1-42) levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) and the Australian, longitudinal AIBL study (n = 576). In the combined sample, the Aß(1-42)/ Aß(1-40) ratio was significantly and inversely associated with SBP (p = 0.03) and a similar trend was observed for DBP (p = 0.06). Using the median age (69) as a cut-off, the Aß(1-42)/Aß(1-40) ratio was strongly associated with both SBP and DBP in elderly individuals (p = 0.002 and p = 0.03, respectively). Consistently, a high Aß(1-42)/ Aß(1-40) ratio was associated with a lower risk of hypertension in both the combined whole sample (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.56-0.90) and (to an even greater extent) in the elderly subjects (OR, 0.53; 95% CI, 0.37-0.75). Lastly, all these associations appeared to be primarily driven by the level of plasma Aß(1-40). CONCLUSION: The plasma Aß(1-42)/Aß(1-40) ratio is inversely associated with SBP, DBP and the risk of hypertension in elderly subjects, suggesting that Aß peptides affect blood pressure in vivo. These results may be particularly relevant in Alzheimer's disease, in which a high Aß(1-42)/Aß(1-40) plasma ratio is reportedly associated with a decreased risk of incident disease.
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ItemFrom rehabilitation to recovery: protocol for a randomised controlled trial evaluating a goal-based intervention to reduce depression and facilitate participation post-stroke(BMC, 2011-06-18)BACKGROUND: There is much discourse in healthcare about the importance of client-centred rehabilitation, however in the realm of community-based therapy post-stroke there has been little investigation into the efficacy of goal-directed practice that reflects patients' valued activities. In addition, the effect of active involvement of carers in such a rehabilitation process and their subsequent contribution to functional and emotional recovery post-stroke is unclear. In community based rehabilitation, interventions based on patients' perceived needs may be more likely to alter such outcomes. In this paper, we describe the methodology of a randomised controlled trial of an integrated approach to facilitating patient goal achievement in the first year post-stroke. The effectiveness of this intervention in reducing the severity of post-stroke depression, improving participation status and health-related quality of life is examined. The impact on carers is also examined. METHODS/DESIGN: Patients (and their primary carers, if available) are randomly allocated to an intervention or control arm of the study. The intervention is multimodal and aims to screen for adverse stroke sequelae and address ways to enhance participation in patient-valued activities. Intervention methods include: telephone contacts, written information provision, home visitation, and contact with treating health professionals, with further relevant health service referrals as required. The control involves treatment as usual, as determined by inpatient and community rehabilitation treating teams. Formal blinded assessments are conducted at discharge from inpatient rehabilitation, and at six and twelve months post-stroke. The primary outcome is depression. Secondary outcome measures include participation and activity status, health-related quality of life, and self-efficacy. DISCUSSION: The results of this trial will assist with the development of a model for community-based rehabilitation management for stroke patients and their carers, with emphasis on goal-directed practice to enhance home and community participation status. Facilitation of participation in valued activities may be effective in reducing the incidence or severity of post-stroke depression, as well as enhancing the individual's perception of their health-related quality of life. The engagement of carers in the rehabilitation process will enable review of the influence of the broader social context on recovery. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12608000042347.
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ItemGenetic Influences on Four Measures of Executive Functions and Their Covariation with General Cognitive Ability: The Older Australian Twins Study(SPRINGER, 2012-07)"Executive functions" (EF) is a multidimensional construct which encompasses many higher-order cognitive control operations, and is considered a potential mediator of age-associated changes in other cognitive domains. Here we examine the heritability of four measures of EF, and the genetic influences on their covariation with general cognitive abilities (GCA) from the Older Australian Twins Study. Participants included 117 pairs of monozygotic twins, 98 pairs of dizygotic twins, and 42 single twins, with a mean age of 71. Genetic modeling showed that additive genetic factors contributed to 59, 63,29, and 31% of the variance in the four measures: working memory, verbal fluency, response inhibition and cognitive flexibility, respectively. The phenotypic associations among the four EF measures were modest, which is in line with other evidence that EF is a multi-dimensional construct.All of the covariation between the EF measures was attributable to a common genetic factor. Similarly, all of the covariation between EF and General Cognitive Ability was explained by a common genetic factor, with no significant covariance due to environmental (E) factors. The genetic correlations between the measures were moderately high, suggesting that they may have common biological underpinnings. The genetic influence in the covariation of the EF measures and GCA also suggests that some aspects of EF and GCA share the same genes or same set of genes.
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ItemDecline in Cognitive Function over 18 Months in Healthy Older Adults with High Amyloid-β(IOS PRESS, 2013)We aimed to characterize the nature and magnitude of cognitive decline in a group of healthy older adults with high and low levels of amyloid-β (Aβ) and who were APOE ε4 carriers and non-carriers. Healthy older adults underwent positron emission tomography neuroimaging for Aβ, APOE genotyping, and cognitive and clinical assessment as part of their baseline assessment in the Australian Imaging, Biomarker, and Lifestyle study. Cognitive function and clinical ratings were reassessed 18 months later. Linear mixed model analyses adjusted for baseline cognitive function indicated that relative to healthy older adults with low Aβ, healthy older adults with high Aβ showed greater decline in episodic memory and language at 18 months. No decline on any measure of executive function, attention, or clinical rating was observed for healthy older adults with high Aβ levels. Compared to non-carriers, APOE ε4 carriers showed a greater decline only on the task of visual memory at the 18 month assessment. Importantly though, no interaction between APOE ε4 and Aβ was observed on any measure of cognitive function. The results of this study suggest that high Aβ load was associated with greater decline in episodic memory and language, that the magnitude of this decline was moderate and equivalent across both domains, and that APOE ε4 carriage did not moderate the relationship between Aβ and decline in memory and language functions.
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ItemIncreased Risk of Cognitive Impairment in Patients With Diabetes Is Associated With Metformin(AMER DIABETES ASSOC, 2013-10)OBJECTIVE: To investigate the associations of metformin, serum vitamin B12, calcium supplements, and cognitive impairment in patients with diabetes. RESEARCH DESIGN AND METHODS: Participants were recruited from the Primary Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, and the Barwon region of southeastern Australia. Patients with Alzheimer disease (AD) (n=480) or mild cognitive impairment (n=187) and those who were cognitively intact (n=687) were included; patients with stroke or with neurodegenerative diseases other than AD were excluded. Subgroup analyses were performed for participants who had either type 2 diabetes (n=104) or impaired glucose tolerance (n=22). RESULTS: Participants with diabetes (n=126) had worse cognitive performance than participants who did not have diabetes (n=1,228; adjusted odds ratio 1.51 [95% CI 1.03-2.21]). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05-4.75]). After adjusting for age, sex, level of education, history of depression, serum vitamin B12, and metformin use, participants with diabetes who were taking calcium supplements had better cognitive performance (0.41 [0.19-0.92]). CONCLUSIONS: Metformin use was associated with impaired cognitive performance. Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes. Prospective trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin.
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ItemFactors affecting subjective memory complaints in the AIBL aging study: biomarkers, memory, affect, and age(CAMBRIDGE UNIV PRESS, 2013-08)BACKGROUND: The prognostic value of subjective memory complaints (SMCs) in the diagnosis of dementia of the Alzheimer's type is unclear. While some studies have found an association between SMCs and cognitive decline, many have found a stronger association with depression, which raises questions about their diagnostic utility. METHODS: We examined the cross-sectional association between SMC severity (as measured using the MAC-Q, a brief SMC questionnaire) and affect, memory, and Alzheimer's disease (AD) biomarkers (β-amyloid deposition and the apolipoprotein E ε4 (APOEε4) allele) in healthy elderly controls (HC; M = 78.74 years, SD = 6.7) and individuals with mild cognitive impairment (MCI; M = 72.74 years, SD = 8.8). We analyzed a subset of individuals drawn from the Australian Imaging Biomarkers and Lifestyle (AIBL) Study of Aging. RESULTS: SMCs were more severe in MCI patients than in HCs. SMC severity was related to affective variables and the interaction between age and group membership (HC/MCI). Within the HC group, SMC severity was related to affective variables only, while severity correlated only with age in the MCI group. SMCs were not related to cognitive variables or AD biomarkers. CONCLUSION: SMCs were related to solely by poorer mood (greater depressive and anxious symptomatology) in the cognitively healthy elderly however mean levels were subclinical. This finding argues for the assessment of affective symptomatology in conjunction with cognitive assessment in elderly memory complainers. Future AIBL research will focus on assessing other AD biomarkers, such as brain atrophy and Aβ plasma markers, in relation to complaint severity. Once our 36-month follow-up data are collected, we propose to assess whether SMCs can predict future cognitive decline.
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ItemNo Preview AvailableLack of reliable evidence for a distinctive ε4-related cognitive phenotype that is independent from clinical diagnostic status: findings from the Australian Imaging, Biomarkers and Lifestyle Study(OXFORD UNIV PRESS, 2013-07)Individuals who carry the apolipoprotein E ε4 polymorphism have an increased risk of late-onset Alzheimer's disease. However, because possession of the ε4 allele confers an increased risk for the diagnosis of dementia, it has proven problematic in older individuals to dissociate the influence of ε4 on cognitive capacity per se as distinct from its influence on clinical diagnostic status. We report a statistical approach that attempts to partial out the influence of diagnostic group membership (Alzheimer's disease, mild cognitive impairment, healthy control) from the influence of apolipoprotein ε4 genetic status on cognitive functioning. The cognitive phenotype hypothesis predicts that ε4-positive individuals will show cognitive deficits (relative to matched ε4-negative individuals) independent of the development of Alzheimer's disease. By contrast, the prodromal/preclinical Alzheimer's disease hypothesis proposes that the effect of apolipoprotein E status on cognitive performance is a function of the increased risk of dementia in individuals with the ε4 allele. We evaluated these hypotheses in the Australian Imaging, Biomarkers and Lifestyle cohort (n = 1112). We first determined whether previously reported findings concerning ε4 status and age-related neuropsychological performance could be explained by the inadvertent recruitment of people with mild cognitive impairment into the healthy control group. We then tested each diagnostic group in isolation to identify any neuropsychological patterns that may be attributed to the ε4 allele. Finally, as interactions between the ε4 allele and age have previously been reported in cognitive functioning within healthy elderly populations, we attempted to determine whether the inclusion of mild cognitively impaired individuals in the sample may drive this relationship. An extensive battery of standardized, well-validated neuropsychological tasks was administered to a final sample of 764 healthy control subjects, 131 individuals with mild cognitive impairment and 168 individuals with Alzheimer's disease. The effect of the ε4 allele on cognitive performance was assessed using a statistical mediation analysis and supplemented with Bayesian methods to address a number of the limitations associated with Fisherian/Neyman-Pearsonian significance testing. Our findings support the prodromal/preclinical Alzheimer's disease hypothesis and do not support the concept of a distinctive ε4-related cognitive phenotype.
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ItemNo Preview AvailableRegional dynamics of amyloid-β deposition in healthy elderly, mild cognitive impairment and Alzheimer's disease: a voxelwise PiB-PET longitudinal study(OXFORD UNIV PRESS, 2012-07)Amyloid-β deposition in Alzheimer's disease is thought to start while individuals are still cognitively unimpaired and it is hypothesized that after an early phase of fast accumulation, a plateau is reached by the time of cognitive decline. However, few longitudinal Pittsburgh compound B-positron emission tomography studies have tested this hypothesis, and with conflicting results. The purpose of this work is to further our understanding of the dynamics of amyloid-β deposition in a large longitudinal cohort. A total of 32 patients with Alzheimer's disease, 49 subjects with mild cognitive impairment and 103 healthy controls underwent two Pittsburgh compound B-positron emission tomography scans 18 months apart. For each participant, a parametric map of Pittsburgh compound B-positron emission tomography rate of change was created [(follow-up scan - baseline scan)/follow-up duration] and entered in a voxelwise three-way analysis of covariance, with clinical status (healthy controls, mild cognitive impairment or Alzheimer's disease), disease progression (clinical conversion from healthy controls to mild cognitive impairment or Alzheimer's disease, or from mild cognitive impairment to Alzheimer's disease) and Pittsburgh compound B status (positive versus negative) as independent factors. Only a significant effect of the Pittsburgh compound B status was found: both Pittsburgh compound B-positive and -negative subjects showed a significant increase in amyloid-β deposition, with this increase being significantly higher in Pittsburgh compound B-positive individuals. This finding suggests either that Pittsburgh compound B-negative individuals have slower rates of amyloid-β accumulation than positive, or that the proportion of individuals showing significant increase in amyloid-β deposition, termed 'Pittsburgh compound B accumulators', is higher within the Pittsburgh compound B-positive group than within the Pittsburgh compound B-negative group. The bimodal distribution of the individual rates of neocortical amyloid-β accumulation observed support the existence of 'Pittsburgh compound B non-accumulators' and 'Pittsburgh compound B accumulators' and different clustering analyses led to a consistent threshold to separate these two subgroups (0.014-0.022 standardized uptake value ratio(pons)/year). The voxelwise three-way analysis of covariance was thus recomputed with the 'Pittsburgh compound B accumulators' only and the results were almost unchanged, with the Pittsburgh compound B-positive group showing higher accumulation than the Pittsburgh compound B-negative group. Finally, a significant negative correlation was found between Pittsburgh compound B rate of change and Pittsburgh compound B baseline burden, but only in the Pittsburgh compound B-positive group (r= -0.24; P=0.025). Higher rates of amyloid-β deposition are associated with higher amyloid-β burden suggesting that amyloid-β deposition does not reach a plateau when cognitive impairments manifest but is instead an ongoing process present even at the Alzheimer's disease stage. amyloid-β accumulation also seems to slow down at the latest stages of the process, i.e. in participants with the highest amyloid burden. Furthermore, this study identified the existence of Pittsburgh compound 'accumulators' and 'non-accumulators', notably within the Pittsburgh compound B-negative group, which may be a relevant concept for future studies.