Publications by authors named "Osvaldo P Almeida"

266 Publications

The Hospital Frailty Risk Score Identifies Fewer Cases of Frailty in a Community-Based Cohort of Older Men Than the FRAIL Scale and Frailty Index.

J Am Med Dir Assoc 2021 Nov 2. Epub 2021 Nov 2.

Western Australian Centre for Health and Ageing, Medical School, The University of Western Australia, Perth, Western Australia, Australia.

Objectives: The recently developed Hospital Frailty Risk Score (HFRS) allows ascertainment of frailty from administrative data. We aimed to compare the HFRS against the widely used FRAIL Scale and Frailty Index.

Design: Population-based cohort study linked to Western Australian Hospital Morbidity Data Collection and Death Registrations.

Setting And Participants: The Health in Men Study with frailty determined at wave 2 (2001/2004), mortality in the 1-year period following wave 2, and disability at wave 3 (2008). Participants were 4228 community-based men aged ≥75 years, followed until wave 3.

Measurements: We used multivariable regression to determine the association between each frailty measure and outcomes of length of stay (LOS), death, and disability. We also determined if the additional cases of frailty identified by one measure over the other was associated with these outcomes.

Results: Of 4228 men studied, the HFRS (n = 689) identified fewer men as frail than the FRAIL Scale (n = 1648) and Frailty Index (n = 1820). In the fully adjusted models, all 3 frailty measures were associated with longer LOS and mortality, whereas only the FRAIL Scale and Frailty Index were significantly associated with disability. The additional cases of frailty identified by the FRAIL Scale and Frailty Index had longer LOS and greater risks of death and disability. The fully adjusted hazard ratio for death among the additional cases of frailty identified by the FRAIL Scale (compared to being not frail on both HFRS and FRAIL Scale) was 2.14 (95% CI 1.48-3.08).

Conclusions And Implications: The HFRS is associated with adverse outcomes. However, it identified approximately 60% fewer men who were frail than the FRAIL Scale and Frailty Index, and the additional cases identified were also at high risks of adverse outcomes. Users of the HFRS should be aware of the differences with other frailty measures.
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http://dx.doi.org/10.1016/j.jamda.2021.09.033DOI Listing
November 2021

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.

J Alzheimers Dis 2021 ;84(1):207-226

Western Australian Centre for Health and Ageing, Medical School, University of Western Australia, Perth, Australia.

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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http://dx.doi.org/10.3233/JAD-210479DOI Listing
January 2021

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

JAMA Intern Med 2021 Nov;181(11):1440-1450

Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.

Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings.

Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia.

Design, Setting, And Participants: This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021.

Exposures: Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values.

Main Outcomes And Measures: The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated.

Results: Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia.

Conclusions And Relevance: In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.
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http://dx.doi.org/10.1001/jamainternmed.2021.5078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424529PMC
November 2021

Depression Outcomes Among Patients Treated With Fluoxetine for Stroke Recovery: The AFFINITY Randomized Clinical Trial.

JAMA Neurol 2021 Sep;78(9):1072-1079

The George Institute for Global Health, Faculty of Medicine, The University of New South Wales, Camperdown, New South Wales, Australia.

Importance: One in 3 adults experiences clinically significant symptoms of depression during the first year after a stroke, but evidence to support the use of antidepressants in this population remains scant.

Objective: To investigate whether daily treatment with 20 mg of fluoxetine hydrochloride reduces the proportion of people affected by clinically significant symptoms of depression after stroke.

Design, Setting, And Participants: In this secondary analysis of the Assessment of Fluoxetine in Stroke Recovery parallel-group, randomized (1:1 assignment), double-blind, placebo-controlled clinical trial, 1221 participants in Australia, New Zealand, and Vietnam were recruited between January 11, 2013, and June 30, 2019, and were followed up for 6 months. Adults aged 18 years or older were recruited 2 to 15 days after experiencing a stroke associated with modified Rankin Scale score of 1 or higher.

Interventions: Fluoxetine hydrochloride, 20 mg, or matched placebo daily for 26 weeks.

Main Outcomes And Measures: A 9-item Patient Health Questionnaire (PHQ-9) score of 9 or lower was a prespecified secondary outcome of the trial. Assessments were completed at baseline and at 4, 12, and 26 weeks. Other outcomes of interest included participant-reported clinician diagnosis of depression, prescription of a nontrial antidepressant, or nonpharmacologic treatment of depression. Analysis was on an intention-to-treat basis.

Results: A total of 607 participants (378 men [62.3%]; mean [SD] age, 64.3 [12.2] years) were randomly assigned treatment with placebo, and 614 participants (397 men [64.7%]; mean [SD] age, 63.4 [12.4] years) were randomly assigned treatment with 20 mg of fluoxetine hydrochloride daily. The groups were balanced for demographic and clinical measures. At baseline, 112 patients (18.5%) in the placebo group and 116 patients (18.9%) in the fluoxetine group had PHQ-9 scores of 9 or higher. During follow-up, 126 of 596 participants (21.1%) treated with placebo and 121 of 598 participants (20.2%) treated with fluoxetine had PHQ-9 scores of 9 or higher (P = .70). A similar proportion of participants with PHQ-9 scores less than 9 at baseline who were treated with fluoxetine hydrochloride and placebo developed PHQ-9 scores of 9 or higher during the trial (placebo, 72 of 488 [14.8%]; and fluoxetine, 63 of 485 [13.0%]; P = .43). A slightly higher number of participants in the placebo group than in the fluoxetine group had a participant-reported clinician diagnosis of depression (42 of 602 [7.0%] vs 26 of 601 [4.3%]; P = .05). By week 26, 14 participants (2.3%) in the placebo group and 12 participants (1.9%) in the fluoxetine group had died (P = .67).

Conclusions And Relevance: Routine daily treatment with 20 mg of fluoxetine did not decrease the proportion of people affected by clinically significant symptoms of depression after a stroke, nor did it affect the proportion of people prescribed an antidepressant or receiving nonpharmacologic treatments compared with placebo.

Trial Registration: http://anzctr.org.au Identifier: ACTRN12611000774921.
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http://dx.doi.org/10.1001/jamaneurol.2021.2418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329781PMC
September 2021

Bipolar symptoms, somatic burden, and functioning in older-age bipolar disorder: Analyses from the Global Aging & Geriatric Experiments in Bipolar Disorder Database project.

Bipolar Disord 2021 Jul 27. Epub 2021 Jul 27.

Department of Psychiatry, University of California San Diego, San Diego, CA, USA.

Objective: Literature on older-age bipolar disorder (OABD) is limited. This first-ever analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated associations among age, BD symptoms, comorbidity, and functioning.

Methods: This analysis used harmonized, baseline, cross-sectional data from 19 international studies (N = 1377). Standardized measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Global Assessment of Functioning (GAF).

Results: Mean sample age was 60.8 years (standard deviation [SD] 12.2 years), 55% female, 72% BD I. Mood symptom severity was low: mean total YMRS score of 4.3 (SD 5.4) and moderate-to-severe depression in only 22%. Controlled for sample effects, both manic and depressive symptom severity appeared lower among older individuals (p's < 0.0001). The negative relationship between older age and symptom severity was similar across sexes, but was stronger among those with lower education levels. GAF was mildly impaired (mean =62.0, SD = 13.3) and somatic burden was high (mean =2.42, SD = 1.97). Comorbidity burden was not associated with GAF. However, higher depressive (p < 0.0001) and manic (p < 0.0001) symptoms were associated with lower GAF, most strongly among older individuals.

Conclusions: Findings suggest an attenuation of BD symptoms in OABD, despite extensive somatic burden. Depressive symptom severity was strongly associated with worse functioning in older individuals, underscoring the need for effective treatments of BD depression in older people. This international collaboration lays a path for the development of a better understanding of aging in BD.
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http://dx.doi.org/10.1111/bdi.13119DOI Listing
July 2021

Risk of Fractures in Stroke Patients Treated With a Selective Serotonin Reuptake Inhibitor: A Systematic Review and Meta-Analysis.

Stroke 2021 08 25;52(9):2802-2808. Epub 2021 Jun 25.

Medical School, Faculty of Health and Medical Sciences (G.J.H.), The University of Western Australia, Perth, Australia.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.032973DOI Listing
August 2021

Association between hearing loss and frailty: a systematic review and meta-analysis.

BMC Geriatr 2021 05 25;21(1):333. Epub 2021 May 25.

Medical School, University of Western Australia, 35 Stirling Highway, Western Australia, 6009, Perth, Australia.

Background: Frailty is associated with poor health outcomes in later life. Recent studies suggested that hearing loss may be a potentially modifiable risk factor associated with frailty.

Methods: This systematic review and meta-analysis aimed to investigate the association between hearing loss and frailty in observational studies of adults aged 50 years or over. We included observational studies with participants ≥ 50 years old that have clear descriptions of hearing and frailty measurement methods. Meta-analyses were conducted using measurement of risk and 95 % confidence interval of each individual study. Quality assessment, risk of bias, heterogeneity and sensitivity analyses were also conducted. Our study followed PRISMA guidelines.

Results: Our search identified 4508 manuscripts published in English between 1 and 2000 and 9 February 2021. Sixteen articles reported acceptable measurements of both hearing loss and frailty. Two papers were not suitable for meta-analysis. Twelve sets of cross-sectional data involving 12,313 participants, and three sets of longitudinal data involving 3042 participants were used in the meta-analysis. Hearing loss was associated with an 87 % increase in the risk of frailty among cross-sectional studies (risk ratio [RR] 1.87; 95 %CI 1.63-2.13) and 56 % among longitudinal studies (RR 1.56; 95 %CI 1.29-1.88). There was considerable heterogeneity among studies, but their quality rating, sample size or approach used to assess hearing loss did not change the results substantially.

Conclusions: The findings of this systematic review and meta-analysis of observational studies suggest that hearing loss increases the risk of frailty in later life. Whether this relationship is causal remains to be determined.
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http://dx.doi.org/10.1186/s12877-021-02274-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147347PMC
May 2021

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration.

Stroke 2021 08 21;52(8):2502-2509. Epub 2021 May 21.

Hawke's Bay Hospital, Hastings, New Zealand (J.G.).

Background And Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization.

Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months.

Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76-1.14]; =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; =0.64) at 12 months.

Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/; Unique identifier: ACTRN12611000774921.
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http://dx.doi.org/10.1161/STROKEAHA.120.033070DOI Listing
August 2021

Long-term exposure to outdoor air pollution and risk factors for cardiovascular disease within a cohort of older men in Perth.

PLoS One 2021 29;16(3):e0248931. Epub 2021 Mar 29.

School of Population and Global Health, The University of Western Australia, Perth, Australia.

While there is clear evidence that high levels of pollution are associated with increased all-cause mortality and cardiovascular mortality and morbidity, the biological mechanisms that would explain this association are less understood. We examined the association between long-term exposure to air pollutants and risk factors associated with cardiovascular disease. Air pollutant concentrations were estimated at place of residence for cohort members in the Western Australian Centre for Health and Ageing Health in Men Study. Blood samples and blood pressure measures were taken for a cohort of 4249 men aged 70 years and above between 2001 and 2004. We examined the association between 1-year average pollutant concentrations with blood pressure, cholesterol, triglycerides, C-reactive protein, and total homocysteine. Linear regression analyses were carried out, with adjustment for confounding, as well as an assessment of potential effect modification. The four pollutants examined were fine particulate matter, black carbon (BC), nitrogen dioxide, and nitrogen oxides. We found that a 2.25 μg/m3 higher exposure to fine particulate matter was associated with a 1.1 percent lower high-density cholesterol (95% confidence interval: -2.4 to 0.1) and 4.0 percent higher serum triglycerides (95% confidence interval: 1.5 to 6.6). Effect modification of these associations by diabetes history was apparent. We found no evidence of an association between any of the remaining risk factors or biomarkers with measures of outdoor air pollution. These findings indicate that long-term PM2.5 exposure is associated with elevated serum triglycerides and decreased HDL cholesterol. This requires further investigation to determine the reasons for this association.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248931PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006998PMC
October 2021

Boon or bane? Using antidepressants after stroke.

Maturitas 2021 11 24;153:68-70. Epub 2021 Feb 24.

The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Australia; The University of Central Lancashire, Faculty of Health and Wellbeing, University of Central Lancashire, Preston, UK.

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http://dx.doi.org/10.1016/j.maturitas.2021.02.005DOI Listing
November 2021

COVID-19 and older adults with bipolar disorder: Problems and solutions.

Bipolar Disord 2021 06 12;23(4):420-422. Epub 2021 Mar 12.

GGZ inGeest, Department of Psychiatry, Amsterdam UMC, location VU Medical Center, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.

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http://dx.doi.org/10.1111/bdi.13069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014237PMC
June 2021

Depression and the Risk of Fractures in Later Life: the Health In Men Cohort Study.

Maturitas 2021 Mar 24;145:6-11. Epub 2020 Dec 24.

Medical School, University of Western Australia, Perth, Australia; WA Centre for Health and Ageing of the University of Western Australia, Perth, Australia.

Introduction: Fractures are common and disabling health events, particularly later in life. The presence of clinically significant depressive symptoms has been associated with increased risk of fractures, and we designed the present study to clarify if this association is likely to be causal or due to the confounding effect of measures associated with both fractures and depression.

Method: Cohort study of a community-derived sample of 4224 men aged 70 to 88 years at the start of the follow-up period of up to 17 years. Clinically significant symptoms of depression were defined as a recorded diagnosis of depressive episode in the Western Australian Data Linkage System (WADLS) or by a total score of 7 or greater on the 15-item Geriatric Depression Scale. Health contacts associated with fractures were retrieved from WADLS. Other measures included age, past history of fractures, education, smoking, frailty, poor vision, falls, medications, and the concentration of vitamin D, homocysteine, hsCRP and testosterone. Death was considered a competing risk for fractures.

Results: 911 (21.6%) participants had a bone fracture during follow-up. After adjustment for multiple potential confounders, past and current depression were associated with an increase in the risk of novel fractures; respective odds ratios were 1.41 (95%CI = 1.03, 1.93) and 1.64 (95%CI = 1.20, 2.25). Parsimonious competing risk regression showed that both past and current depression were associated with an increase in the risk of novel fractures: sub-hazard ratio = 1.29 (95%CI = 1.03, 1.63) and 1.27 (95%CI = 1.05, 1.55) respectively. Estimation of confounding due to unmeasured factors showed that a small additional effect could potentially dilute the association between depression and fractures.

Discussion: History of clinically significant symptoms of depression is associated with an increased risk of future fractures. This association may be due to multiple other associated risk factors, both measured and unmeasured, but nevertheless the presence of depression should alert clinicians to the need to develop a management plan that includes the management not only of depression but also of fracture risk.
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http://dx.doi.org/10.1016/j.maturitas.2020.12.004DOI Listing
March 2021

A prospective cohort study of prodromal Alzheimer's disease: Prospective Imaging Study of Ageing: Genes, Brain and Behaviour (PISA).

Neuroimage Clin 2021 8;29:102527. Epub 2020 Dec 8.

QIMR Berghofer Medical Research Institute, Brisbane, Australia; The University of Newcastle, Newcastle, Australia.

This prospective cohort study, "Prospective Imaging Study of Ageing: Genes, Brain and Behaviour" (PISA) seeks to characterise the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer's disease (AD). In particular, we are recruiting midlife and older Australians with high and low genetic risk of dementia to discover biological markers of early neuropathology, identify modifiable risk factors, and establish the very earliest phenotypic and neuronal signs of disease onset. PISA utilises genetic prediction to recruit and enrich a prospective cohort and follow them longitudinally. Online surveys and cognitive testing are used to characterise an Australia-wide sample currently totalling over 3800 participants. Participants from a defined at-risk cohort and positive controls (clinical cohort of patients with mild cognitive impairment or early AD) are invited for onsite visits for detailed functional, structural and molecular neuroimaging, lifestyle monitoring, detailed neurocognitive testing, plus blood sample donation. This paper describes recruitment of the PISA cohort, study methodology and baseline demographics.
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http://dx.doi.org/10.1016/j.nicl.2020.102527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750170PMC
June 2021

Hearing aids to support cognitive functions of older adults at risk of dementia: the HearCog trial- clinical protocols.

BMC Geriatr 2020 11 26;20(1):508. Epub 2020 Nov 26.

Western Australian Centre for Health and Ageing, Medical School, Faculty of Health and Medical Sciences, University of Western Australia, 35 Stirling Highway, Perth, WA, 6009, Australia.

Background: Globally, about 50 million people were living with dementia in 2015, with this number projected to triple by 2050. With no cure or effective treatment currently insight, it is vital that factors are identified which will help prevent or delay both age-related and pathological cognitive decline and dementia. Observational data have suggested that hearing loss is a potentially modifiable risk factor for dementia, but no conclusive evidence from randomised controlled trials is currently available.

Methods: The HearCog trial is a 24-month, randomised, controlled clinical trial aimed at determining whether a hearing loss intervention can delay or arrest the cognitive decline. We will randomise 180 older adults with hearing loss and mild cognitive impairment to a hearing aid or control group to determine if the fitting of hearing aids decreases the 12-month rate of cognitive decline compared with the control group. In addition, we will also determine if the expected clinical gains achieved after 12 months can be sustained over an additional 12 months and if losses experienced through the non-correction of hearing loss can be reversed with the fitting of hearing aids after 12 months.

Discussion: The trial will also explore the cost-effectiveness of the intervention compared to the control arm and the impact of hearing aids on anxiety, depression, physical health and quality of life. The results of this trial will clarify whether the systematic correction of hearing loss benefits cognition in older adults at risk of cognitive decline. We anticipate that our findings will have implications for clinical practice and health policy development.

Trial Registration: Australian and New Zealand Clinical Trials Registry ( ANZCTR: 12618001278224 ), registered on 30.07.2018.
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http://dx.doi.org/10.1186/s12877-020-01912-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690174PMC
November 2020

Obstructive sleep apnea and depression: A systematic review and meta-analysis.

Maturitas 2020 Dec 8;142:45-54. Epub 2020 Jun 8.

WA Centre for Health & Ageing, Medical School, Faculty of Health & Medical Sciences, University of Western Australia, Perth, Australia.

Introduction: The present study aimed to review the association between obstructive sleep apnea (OSA) and depression and compare the prevalence of depression among people with and without OSA.

Methods: Systematic review and meta-analysis following PRISMA guidelines. We searched for papers published between 1 January 2010 and 20 October 2019 listed on the following databases: Embase, Ovid MEDLINER(R) and PsychINFO. The search terms included a combination of keywords related to sleep apnea and depression. We also completed a manual search of the references listed in the articles retrieved and grouped them according to study design: cross-sectional, case-control and longitudinal. Scale scores were standardised for comparison.

Results: Our search strategy yielded 1158 papers, of which 34 were considered suitable of review and 11 reported data that could be used for meta-analysis. Data from the 6 cross-sectional studies found no compelling evidence of an association between OSA and depression (odds ratio = 1.12, 95 % confidence interval, 95 %CI = 0.78, 1.47), but the meta-analysis of 5 longitudinal studies indicated that people with OSA were at greater risk of developing depression during follow-up than those without OSA (non-specific risk ratio (RR) = 2.18, 95 %CI = 1.47, 2.88), although there was evidence of high study heterogeneity (I = 72.8 %).

Discussion: The results of this systematic review and meta-analysis of observational studies is consistent with the hypothesis that OSA may increase the risk of depression. Sample characteristics and various methodological issues create uncertainty about the validity and generalizability of these associations.
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http://dx.doi.org/10.1016/j.maturitas.2020.06.002DOI Listing
December 2020

An individual participant data analysis of prospective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms.

Sci Rep 2020 11 5;10(1):19111. Epub 2020 Nov 5.

Institute of Primary Health Care (BIHAM), University of Bern, Mittelstrasse 43, 3012, Bern, Switzerland.

In subclinical hypothyroidism, the presence of depressive symptoms is often a reason for starting levothyroxine treatment. However, data are conflicting on the association between subclinical thyroid dysfunction and depressive symptoms. We aimed to examine the association between subclinical thyroid dysfunction and depressive symptoms in all prospective cohorts with relevant data available. We performed a systematic review of the literature from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to 10th May 2019. We included prospective cohorts with data on thyroid status at baseline and depressive symptoms during follow-up. The primary outcome was depressive symptoms measured at first available follow-up, expressed on the Beck's Depression Inventory (BDI) scale (range 0-63, higher values indicate more depressive symptoms, minimal clinically important difference: 5 points). We performed a two-stage individual participant data (IPD) analysis comparing participants with subclinical hypo- or hyperthyroidism versus euthyroidism, adjusting for depressive symptoms at baseline, age, sex, education, and income (PROSPERO CRD42018091627). Six cohorts met the inclusion criteria, with IPD on 23,038 participants. Their mean age was 60 years, 65% were female, 21,025 were euthyroid, 1342 had subclinical hypothyroidism and 671 subclinical hyperthyroidism. At first available follow-up [mean 8.2 (± 4.3) years], BDI scores did not differ between participants with subclinical hypothyroidism (mean difference = 0.29, 95% confidence interval =  - 0.17 to 0.76, I = 15.6) or subclinical hyperthyroidism (- 0.10, 95% confidence interval =  - 0.67 to 0.48, I = 3.2) compared to euthyroidism. This systematic review and IPD analysis of six prospective cohort studies found no clinically relevant association between subclinical thyroid dysfunction at baseline and depressive symptoms during follow-up. The results were robust in all sensitivity and subgroup analyses. Our results are in contrast with the traditional notion that subclinical thyroid dysfunction, and subclinical hypothyroidism in particular, is associated with depressive symptoms. Consequently, our results do not support the practice of prescribing levothyroxine in patients with subclinical hypothyroidism to reduce the risk of developing depressive symptoms.
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http://dx.doi.org/10.1038/s41598-020-75776-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644764PMC
November 2020

Preventing depression among older people living in rural areas: A randomised controlled trial of behavioural activation in collaborative care.

Int J Geriatr Psychiatry 2021 04 31;36(4):530-539. Epub 2020 Oct 31.

WA Centre for Rural Health, School of Population and Global Health, University of Western Australia, Perth, Australia.

Objectives: This study aimed to test if a behavioural activation (BA) programme was more effective than usual care at reducing the risk of conversion to major depression over 52 weeks among adults aged 65 years or older living in rural Western Australia. Secondary aims were to test if participants assigned to the BA intervention experienced greater decline in the severity of depressive and anxiety symptoms than older adults treated with usual care over 26 and 52 weeks, as well as greater improvement in physical and mental health-related quality of life.

Methods: Randomised controlled clinical trial that started recruitment in February 2016 in rural Western Australia. We used the electoral roll to invite adults aged 65 years or over living in suitable regions of Western Australia to take part in the study. We recruited those who consented and screened positive to at least one of the two Whooley questions: feeling down/depressed/hopeless or little interest or pleasure over the past month. Participants were randomly assigned to usual care or usual care plus a phone-delivered BA program (1:1). The intervention consisted of a self-managed BA program supported by three 45-min phone sessions delivered by a BA therapist over a period of 8 weeks. We used the DSM-5 criteria to establish the presence of a major depressive episode, and Patient Health Questionnaire, Generalised Anxiety Disorder Scale and SF-36 to assess symptoms of depression, anxiety and quality of life.

Results: Of the 309 older adults randomised, 307 started the trial: 153 usual care and 154 BA (computer-generated random permuted even blocks ranging in size from 8 to 20). Six participants developed a major depressive episode during follow-up, four of them in the usual care group (odds ratio of depression associated with the intervention = 0.49, 95% CI = 0.04, 3.49-blind assessment). Seventy-three (23.8%) participants were lost over 52 weeks-there were no differences between usual care and intervention group. Intention-to-treat analyses using mixed regression models found modest non-significant effects of the BA intervention, while complete-case analyses showed that participants treated with BA compared with usual care experienced significant improvements in depression and anxiety symptoms over 52 weeks, as well as improved mental health quality of life.

Conclusions: Few participants developed a major depressive episode during follow-up. The BA intervention was associated with improved symptoms of depression and anxiety, although the clinical significance of these benefits remains unclear.
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http://dx.doi.org/10.1002/gps.5449DOI Listing
April 2021

U-Shaped Relationship of Leukocyte Telomere Length With All-Cause and Cancer-Related Mortality in Older Men.

J Gerontol A Biol Sci Med Sci 2021 01;76(1):164-171

PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.

Background: Telomeres are essential DNA-protein complexes whose attrition results in cellular dysfunction and senescence. Leukocyte telomere length (LTL) correlates with tissue telomere length, representing a biomarker for biological age. However, its predictive value for mortality risk, and for cardiovascular versus cancer deaths, in older adults remains uncertain.

Method: We studied 3608 community-dwelling men aged 77.0 ± 3.6 years. Leukocyte telomere length was measured using multiplex quantitative PCR, expressed as amount of telomeric DNA relative to single-copy control gene (T/S ratio). Deaths from any cause, cardiovascular disease (CVD), and cancer were ascertained using data linkage. Curve fitting used restricted cubic splines and Cox regression analyses adjusted for age, cardiometabolic risk factors, and prevalent disease.

Results: There was a U-shaped association of LTL with all-cause mortality. Men with T/S ratio in the middle quartiles had lower mortality (quartiles, Q2 vs Q1, hazard ratio [HR] = 0.86, 95% confidence interval [CI] 0.77-0.97, p = .012; Q3 vs Q1 HR = 0.88, CI 0.79-0.99, p = .032). There was no association of LTL with CVD mortality. There was a U-shaped association of LTL with cancer mortality. Men with LTL in the middle quartiles had lower risk of cancer death (Q2 vs Q1, HR = 0.73, CI 0.59-0.90, p = .004; Q3 vs Q1, HR = 0.75, CI 0.61-0.92, p = .007).

Conclusions: In older men, both shorter and longer LTL are associated with all-cause mortality. A similar U-shaped association was seen with cancer deaths, with no association found for cardiovascular deaths. Further research is warranted to explore the prognostic utility of LTL in ageing.
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http://dx.doi.org/10.1093/gerona/glaa190DOI Listing
January 2021

Effect of biological treatments on psychotic symptoms in lewy body disease: A systematic review and meta-analysis of randomized controlled trials.

Int J Geriatr Psychiatry 2020 10 9;35(10):1083-1096. Epub 2020 Aug 9.

WA Centre for Health and Ageing, Medical School, University of Western Australia, Perth, Australia.

Objectives: Parkinson disease and dementia with Lewy bodies (collectively termed Lewy body disease) are common neurodegenerative conditions of later life and are frequently associated with distressing psychotic symptoms. The best approach to manage these symptoms is yet to be established and current treatments carry the risk of serious adverse effects.

Methods: We performed a systematic review and meta-analysis of 19 randomized controlled trials investigating the efficacy of biological treatments for psychotic symptoms in Lewy body disease.

Results: The summary effect estimate did not show a statistically significant benefit of biological treatments for psychotic symptoms in Lewy body disease (SMD -0.48, 95%CI -1.01 to 0.04). This was irrespective of the choice of intervention (SMD -0.53, 95%CI -1.20 to 0.14 for antipsychotic trials) or disease status (SMD -0.59, 95%CI -1.24 to 0.05 for trials of Parkinson disease). There was a significant effect for biological treatments compared with placebo in trials that lasted at least 6 weeks (SMD -0.25, 95%CI -0.43 to -0.08) and those with sample sizes greater than 100 participants (SMD of -0.28 95%CI -0.45 to -0.11).

Conclusions: In this systematic review and meta-analysis, treatment of psychotic symptoms by biological means did not improve symptoms compared with placebo. Small sample sizes, modest treatment durations, and other methodological differences across the trials do make it difficult to draw firm conclusions. Longer, adequately powered trials utilizing established and novel treatments are needed to provide more definitive evidence to guide clinicians in the best choice of agent to treat these distressing and often persistent symptoms.
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http://dx.doi.org/10.1002/gps.5376DOI Listing
October 2020

U-Shaped Association of Plasma Testosterone, and no Association of Plasma Estradiol, with Incidence of Fractures in Men.

J Clin Endocrinol Metab 2020 05;105(5)

Medical School, University of Western Australia, Perth, Western Australia.

Purpose: Whether androgens, distinct from estrogen, maintain bone health during male aging has implications for understanding osteoporosis. We assessed associations of different sex hormones with incidence of any bone fracture or hip fracture in older men.

Participants And Methods: Analysis of 3307 community-dwelling men aged 76.8 ± 3.5 years, median follow-up period of 10.6 years. Plasma testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) assayed by mass spectrometry, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) using immunoassay. Incident fractures determined via data linkage. We analyzed probability of fracture and performed Cox regression adjusted for age, medical comorbidities, and frailty.

Results: Incident fractures occurred in 330 men, including 144 hip fractures. Probability plots suggested nonlinear relationships between hormones and risk of any fracture and hip fracture, with higher risk at lower and higher plasma T, lower E2, higher SHBG, and higher LH. In fully adjusted models, there was a U-shaped association of plasma T with incidence of any fracture (Quartile 2 [Q2] versus Q1: fully adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI] 0.51-0.94, P = .020; Q3: HR 0.59, 95% CI 0.42-0.83, P = .002) and hip fracture (Q2 versus Q1: HR 0.60, 95% CI 0.37-0.93, P = .043; Q3: HR 0.52, 95% CI 0.31-0.88, P = .015). DHT, E2, and LH were not associated with fracture. Higher SHBG was associated with hip fracture (Q4 versus Q1: HR 1.76, 95% CI 1.05-2.96, P = .033).

Conclusions: Midrange plasma T was associated with lower incidence of any fracture and hip fracture, and higher SHBG with increased risk of hip fracture. Circulating androgen rather than estrogen represents a biomarker for hormone effects on bone driving fracture risk.
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http://dx.doi.org/10.1210/clinem/dgaa115DOI Listing
May 2020

Are We Getting Better at Managing Agitation in Dementia?

Am J Geriatr Psychiatry 2020 04 15;28(4):401-403. Epub 2019 Nov 15.

WA Centre for Health and Ageing, Medical School, University of Western Australia, Perth, WA, Australia.

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http://dx.doi.org/10.1016/j.jagp.2019.11.004DOI Listing
April 2020

Behavioural activation in nursing homes to treat depression (BAN-Dep): study protocol for a pragmatic randomised controlled trial.

BMJ Open 2019 10 31;9(10):e032421. Epub 2019 Oct 31.

Medical School, University of Western Australia Faculty of Medicine Dentistry and Health Sciences, Perth, Western Australia, Australia

Introduction: Depression is a common disorder among older people living in residential aged care facilities. Several trials have demonstrated the effectiveness of behavioural therapies in treating depressive symptoms in older adults living in the community and in residential aged care. Behavioural Activation is demonstrably effective even when delivered by non-specialists (staff without formal psychological training), although strategies for adapting its use in residential aged care facilities are yet to be explored. This study will determine whether training residential care staff in the use of a structured Behavioural Activation programme is more effective at decreasing depressive symptoms among older residents than internet-based training about depression recognition and management alone.

Method And Analysis: The behavioural activation in nursing homes to treat depression (BAN-Dep) trial is a pragmatic two-arm parallel clustered randomised controlled trial. It will recruit 666 residents aged 60 or older from 100 residential aged care facilities, which will be randomly assigned to the Behavioural Activation or control intervention. Staff in both treatment groups will be encouraged to complete the Professional Education to Aged Care e-learning programme to improve their recognition of and ability to respond to depression in older adults. Selected staff from intervention facilities will undergo additional training to deliver an 8-module Behavioural Activation programme to residents with subthreshold symptoms of depression-they will receive ongoing Mental support from trained Behavioural Activation therapists. Outcome measures will be collected by blind research officer at baseline and after 3, 6 and 12 months. The Patient Health Questionnaire-9 is the primary outcome measure of the study.

Ethics And Dissemination: The trial will comply with the principles of the Declaration of Helsinki for Human Rights and is overseen by the University of Western Australia (reference RA/4/20/4234) and Melbourne Health (reference number HREC/18/MH/47) Ethics Committees. The results of this research project will be disseminated through publications and/or presentations in a variety of media to health professionals, academics, clinicians and the public. Only de-identified group data will be presented.

Trial Registration: ACTRN12618000634279.
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http://dx.doi.org/10.1136/bmjopen-2019-032421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830697PMC
October 2019

Associations of plasma IGF1, IGFBP3 and estradiol with leucocyte telomere length, a marker of biological age, in men.

Eur J Endocrinol 2020 Jan;182(1):23-33

PathWest Laboratory Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.

Objective: Effects of insulin-like growth factor 1 (IGF1) and its binding proteins (IGFBPs) on ageing, and their interaction with sex hormones, remain uncertain. We examined associations of plasma IGF1, IGFBP1, IGFBP3, estradiol and testosterone, with leucocyte telomere length (LTL), a marker of biological age, in 2999 community-dwelling men aged 70-84 years.

Methods: Plasma IGF1, IGFBP1 and IGFBP3 measured using immunoassay, sex hormones using mass spectrometry. LTL measured by PCR, expressed as ratio of telomeric to single-copy control gene DNA (T/S ratio). Linear regression models adjusted for age and cardio-metabolic risk factors, median splits defined low/high groups.

Results: Mean age was 76.7 ± 3.2 years. IGF1 and IGFBP3 showed age-adjusted correlations with LTL (coefficient 0.59, P = 0.001 and 0.45, P = 0.013 respectively), IGFBP1 did not. In multivariable-adjusted models IGF1 and IGFBP3 (but not IGFBP1) were associated with LTL (T/S ratio 0.015 higher per 1 s.d. increase in IGF1, P = 0.007, and 0.011 per 1 s.d. IGFBP3, P = 0.049). IGF1 and estradiol were independently associated with longer telomeres (T/S ratio 0.012 higher per 1 s.d. increase in estradiol, P = 0.027, when included in model with IGF1). Testosterone was not associated with LTL. Men with both high IGF1 (>133 µg/L) and high estradiol (>70 pmol/L) had longer LTL compared to men with lower values (multivariable-adjusted T/S ratio 1.20 vs 1.16, P = 0.018).

Conclusions: Higher IGF1 and IGFBP3 are independently associated with longer telomeres in older men. Additive associations of higher IGF1 and higher estradiol with telomere length are present. Further studies are needed to determine whether these hormonal exposures cooperate to slow biological aging.
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http://dx.doi.org/10.1530/EJE-19-0638DOI Listing
January 2020

The Healthy Heart-Mind Trial: Randomized Controlled Trial of Melatonin for Prevention of Delirium.

J Am Geriatr Soc 2020 01 8;68(1):112-119. Epub 2019 Oct 8.

Medical School, University of Western Australia, Perth, Western Australia, Australia.

Objectives: Delirium is a serious medical condition with increased incidence in at-risk surgical populations. We sought to determine if melatonin use reduces the incidence of delirium in individuals undergoing major cardiac surgery.

Design: Randomized double-blind placebo-controlled clinical trial (two arms, 1:1 allocation, parallel design).

Setting: The trial took place in two metropolitan hospitals (public tertiary and private) in Perth, Western Australia.

Participants: We recruited 210 adults aged 50 years or older who were due to undergo coronary artery bypass grafting or valve replacement surgery.

Intervention: Participants were randomly assigned (1:1) to 7 days of treatment with melatonin 3 mg at night or matching placebo, starting 2 days before the surgery.

Measurements: The primary outcome of interest was incident delirium within 7 days of surgery as assessed via daily clinical assessment that included the Confusion Assessment Method. Secondary outcomes of interest included duration and severity of delirium, length of hospital stay, cognitive function, and mood and anxiety symptoms at discharge and 3 months after the surgery.

Results: The groups were well balanced for demographic and clinical parameters. Forty-two participants developed delirium, but it was evenly distributed between the groups (melatonin 21/98, 21.4%; placebo 21/104, 20.2%; adjusted odds ratio [OR] = .78; 95% confidence interval [CI] = .35-1.75). The median duration of delirium was 3 (interquartile range [IQR] = 2-4) and 2 (IQR = 1-3) days for people treated with melatonin and placebo, respectively (z = -1.03; P = .304). A similar proportion of participants experienced severe episodes of delirium in each group (melatonin 9/21, 42.9% vs placebo 6/21, 28.6%; χ = .93; P = .334; adjusted OR = 1.98; 95% CI = .40-9.78). The groups did not differ in terms of length of stay, mood, anxiety, and cognitive performance.

Conclusion: The findings of this randomized double-blind placebo-controlled trial do not support the prophylactic use of melatonin to prevent delirium after major cardiac surgery. J Am Geriatr Soc 68:112-119, 2019.
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http://dx.doi.org/10.1111/jgs.16162DOI Listing
January 2020

Depression, antidepressants and the risk of cardiovascular events and death in older men.

Maturitas 2019 Oct 28;128:4-9. Epub 2019 Jun 28.

Medical School, University of Western Australia, Perth, Australia; WA Centre for Health and Ageing of the University of Western Australia, Perth, Australia.

Introduction: It is uncertain whether depression and exposure to antidepressants increase the risk of cardiovascular events in later life. This study attempts to clarify whether the risk of cardiovascular events associated with exposure to antidepressant medications varies according to history of depression.

Methods: Cohort study of 5522 Australian men aged 70-89 years living in the metropolitan region of Perth, Western Australia, who were followed for novel cardiovascular events over 12 years. Clinical diagnoses followed the International Classification of Diseases (ICD) codes for ischaemic heart disease, cerebrovascular events and depressive disorders. Participants self-reported their use of medications. Other study measures included age, schooling, smoking history and the following concurrent morbidities: diabetes, hypertension, cancer, dementia, and respiratory diseases, gastrointestinal and renal diseases.

Results: 374 men (6.8%) had a recorded or current diagnosis of depression and 365 (6.6%) were using an antidepressant. Prevalent depression and antidepressant use were associated with increased mortality hazard, but not the interaction between them (hazard ratio, HR = 0.46, 95%CI = 0.33, 0.65). Depression (HR = 1.50, 95%CI = 1.21, 1.86) and antidepressants (HR = 1.52, 95%CI = 1.20, 1.93) were associated with an increased risk of cardiovascular events, but the interaction term was associated with decreased risk (HR = 0.51, 95%CI = 0.30, 0.87). All analyses were adjusted for other study measures.

Discussion: Depression and antidepressant use were associated with an increase in the 12-year risk of cardiovascular events, while antidepressants were associated with a decrease in the risk of cardiovascular events among older men with depression, but not among those without. This suggests that the effect of this interaction on the risk of cardiovascular events may be driven by the ability of antidepressants to lead to clinical improvements in mood.
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http://dx.doi.org/10.1016/j.maturitas.2019.06.009DOI Listing
October 2019

Cognitive bias modification to prevent depression (COPE): results of a randomised controlled trial.

Psychol Med 2020 11 23;50(15):2514-2525. Epub 2019 Sep 23.

Medical School, The University of Western Australia, Western Australia, Australia.

Background: Although efficacious treatments for major depression are available, efficacy is suboptimal and recurrence is common. Effective preventive strategies could reduce disability associated with the disorder, but current options are limited. Cognitive bias modification (CBM) is a novel and safe intervention that attenuates biases associated with depression. This study investigated whether the delivery of a CBM programme designed to attenuate negative cognitive biases over a period of 1 year would decrease the incidence of major depression among adults with subthreshold symptoms of depression.

Methods: Randomised double-blind controlled trial delivered an active CBM intervention or a control intervention over 52 weeks. Two hundred and two community-dwelling adults who reported subthreshold levels of depression were randomised (100 intervention, 102 control). The primary outcome of interest was the incidence of major depressive episode assessed at 11, 27 and 52 weeks. Secondary outcomes included onset of clinically significant symptoms of depression, change in severity of depression symptoms and change in cognitive biases.

Results: Adherence to the interventions was modest though did not differ between conditions. Incidence of major depressive episodes was low. Conditions did not differ in the incidence of major depressive episodes. Likewise, conditions did not differ in the incidence of clinically significant levels of depression, change in the severity of depression symptoms or change in cognitive biases.

Conclusions: Active CBM intervention did not decrease the incidence of major depressive episodes as compared to a control intervention. However, adherence to the intervention programme was modest and the programme failed to modify the expected mechanism of action.
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http://dx.doi.org/10.1017/S0033291719002599DOI Listing
November 2020

The Challenge of Treating Depression in Dementia.

Am J Geriatr Psychiatry 2019 09 10;27(9):932-933. Epub 2019 May 10.

Western Australian Centre for Health & Ageing, Medical School, University of Western Australia, Perth, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.jagp.2019.05.004DOI Listing
September 2019

The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project: Understanding older-age bipolar disorder by combining multiple datasets.

Bipolar Disord 2019 11 30;21(7):642-649. Epub 2019 May 30.

GGZ inGeest, Amsterdam UMC, location VU Medical Center, Amsterdam Neuroscience, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.

Objective: There is a dearth of research about the aging process among individuals with bipolar disorder (BD). One potential strategy to overcome the challenge of interpreting findings from existing limited older-age bipolar disorder (OABD) research studies is to pool or integrate data, taking advantage of potential overlap or similarities in assessment methods and harmonizing or cross-walking measurements where different measurement tools are used to evaluate overlapping construct domains. This report describes the methods and initial start-up activities of a first-ever initiative to create an integrated OABD-focused database, the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project.

Methods: Building on preliminary work conducted by members of the International Society for Bipolar Disorders OABD taskforce, the GAGE-BD project will be operationalized in four stages intended to ready the dataset for hypothesis-driven analyses, establish a consortium of investigators to guide exploration, and set the stage for prospective investigation using a common dataset that will facilitate a high degree of generalizability.

Results: Initial efforts in GAGE-BD have brought together 14 international investigators representing a broad geographic distribution and data on over 1,000 OABD. Start-up efforts include communication and guidance on meeting regulatory requirements, establishing a Steering Committee to guide an incremental analysis strategy, and learning from existing multisite data collaborations and other support resources.

Discussion: The GAGE-BD project aims to advance understanding of associations between age, BD symptoms, medical burden, cognition and functioning across the life span and set the stage for future prospective research that can advance the understanding of OABD.
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http://dx.doi.org/10.1111/bdi.12795DOI Listing
November 2019

Differential associations of ferritin and 25-hydroxyvitamin D with fasting glucose and diabetes risk in community dwelling older men.

Diabetes Metab Res Rev 2019 10 10;35(7):e3172. Epub 2019 Jun 10.

Medical School, University of Western Australia, Perth, Australia.

Aims: We examined associations of ferritin and 25-hydroxyvitamin D with fasting glucose and prevalent diabetes in older men.

Methods: Cross-sectional analysis of 4153 community-dwelling men aged 70 to 89 years in Western Australia. Plasma ferritin, 25-hydroxyvitamin D, and glucose were assayed. Diabetes was ascertained from self-report, medications, and fasting glucose.

Results: There were 577 men with diabetes (13.9%). In the whole cohort, ferritin was associated with fasting glucose (0.051 mmol/L per 1 SD increase in ferritin, P = .006) and 25-hydroxyvitamin D was inversely associated (-0.085 mmol/L per 1 SD, P < .001). Ferritin was not associated with prevalent diabetes (highest vs. lowest quartile; >225 vs <66 μg/L: adjusted odds ratio [OR] 0.97, 95% confidence interval [CI], 0.74-1.27, P = .83). Higher vitamin D was associated with decreased odds of prevalent diabetes (highest vs lowest quartile; >82 nmol/L vs <53 nmol/L: OR = 0.57, 95% CI = 0.43-0.75, P < .001). There was no interaction between ferritin and vitamin D on diabetes risk.

Conclusions: In older men, ferritin is associated with fasting glucose but not prevalent diabetes. Higher 25-hydroxyvitamin D concentrations are independently associated with lower fasting glucose and reduced risk of diabetes. Clinical trials are required to determine whether interventions, which raise vitamin D concentrations, would reduce incidence of diabetes in this expanding demographic group.
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http://dx.doi.org/10.1002/dmrr.3172DOI Listing
October 2019
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