Publications by authors named "Nicolas Cherbuin"

150 Publications

Trajectories of depression and anxiety symptoms during the COVID-19 pandemic in a representative Australian adult cohort.

Med J Aust 2021 Apr 26. Epub 2021 Apr 26.

Australian National University, Canberra, ACT.

Objectives: To estimate initial levels of symptoms of depression and anxiety, and their changes during the early months of the COVID-19 pandemic in Australia; to identify trajectories of symptoms of depression and anxiety; to identify factors associated with these trajectories.

Design, Setting, Participants: Longitudinal cohort study; seven fortnightly online surveys of a representative sample of 1296 Australian adults from the beginning of COVID-19-related restrictions in late March 2020 to mid-June 2020.

Main Outcome Measures: Symptoms of depression and anxiety, measured with the Patient Health Questionnaire (PHQ-9) depression and Generalised Anxiety Disorder (GAD-7) scales; trajectories of symptom change.

Results: Younger age, being female, greater COVID-19-related work and social impairment, COVID-19-related financial distress, having a neurological or mental illness diagnosis, and recent adversity were each significantly associated with higher baseline depression and anxiety scores. Growth mixture models identified three latent trajectories for depression symptoms (low throughout the study, 81% of participants; moderate throughout the study, 10%; initially severe then declining, 9%) and four for anxiety symptoms (low throughout the study, 77%; initially moderate then increasing, 10%; initially moderate then declining, 5%; initially mild then increasing before again declining, 8%). Factors statistically associated with not having a low symptom trajectory included mental disorder diagnoses, COVID-19-related financial distress and social and work impairment, and bushfire exposure.

Conclusion: Our longitudinal data enabled identification of distinct symptom trajectories during the first three months of the COVID-19 pandemic in Australia. Early intervention to ensure that vulnerable people are clinically and socially supported during a pandemic should be a priority.
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http://dx.doi.org/10.5694/mja2.51043DOI Listing
April 2021

The role of cognition and reinforcement sensitivity in older adult decision-making under explicit risk conditions.

J Clin Exp Neuropsychol 2021 Apr 26:1-17. Epub 2021 Apr 26.

School of Psychology, University of New South Wales, Sydney, Australia.

: Previous research has suggested that individual differences in executive functions, memory and reinforcement sensitivity are associated with performance on behavioral decision-making tasks. Decision-making performance may also decline with age, however there is a lack of research on the interplay of cognitive and affective processes, and their impact on older adult decision-making. This study examined associations between executive functions, memory and reinforcement sensitivity on the Game of Dice Task (a measure of decision-making under explicit risk) among older adults.: One thousand and two older adults without cognitive impairment (aged 72-78 years) participated as part of an Australian longitudinal cohort study (the Personality and Total Health Through Life study). Decision-making sub-types were identified through cluster analysis and multinomial logistic regression was used to assess associations with measures of cognition and reinforcement sensitivity.: Cluster analysis identified three decision-making sub-types, which we label "advantageous," "disadvantageous" and "switching." Multivariate analyses found that relative to the mid-performing "switching" sub-type, advantageous decision-makers were more likely to be younger, male and have higher scores on a test of verbal learning. Disadvantageous decision-makers were more likely to have poorer scores on some components of executive function (set shifting, but not working memory or inhibitory control), although this effect was partly attenuated by a measure of reinforcement sensitivity (reward responsiveness).: These results indicate that specific components of learning and executive functions are influential in decision-making under explicit risk among a sample of older adults.
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http://dx.doi.org/10.1080/13803395.2021.1909709DOI Listing
April 2021

Commissioning of an ultra-high dose rate pulsed electron beam medical LINAC for FLASH RT pre-clinical animal experiments and future clinical human protocols.

Med Phys 2021 Apr 18. Epub 2021 Apr 18.

Institute of Radiation Physics, Lausanne University Hospital, Lausanne, Switzerland.

Purpose: To present the acceptance and the commissioning, to define the reference dose, and to prepare the reference data for a quality assessment (QA) program of an ultra-high dose rate (UHDR) electron device in order to validate it for pre-clinical animal FLASH radiotherapy (FLASH RT) experiments and for FLASH RT clinical human protocols.

Methods: The Mobetron device was evaluated with electron beams of 9 MeV in conventional (CONV) mode and of 6 MeV and 9 MeV in UHDR mode (nominal energy). The acceptance was performed according to the acceptance protocol of the company. The commissioning consisted of determining the short- and long-term stability of the device, the measurement of percent depth dose curves (PDDs) and profiles at two different positions (with two different dose per pulse regimen) and for different collimator sizes, and the evaluation of the variability of these parameters when changing the pulse width and pulse repetition frequency. Measurements were performed using a redundant and validated dosimetric strategy with alanine and radiochromic films, as well as Advanced Markus ionization chamber for some measurements.

Results: The acceptance tests were all within the tolerances of the company's acceptance protocol. The linearity with pulse width was within 1.5% in all cases. The pulse repetition frequency (PRF) did not affect the delivered dose more than 2% in all cases but 90 Hz, for which the larger difference was 3.8%. The reference dosimetry showed a good agreement within the alanine and films with variations of 2.2% or less. The short-term (resp. long-term) stability less than 1.0% (resp. 1.8%) and were the same in both the CONV and UHDR modes. PDDs, profiles, and reference dosimetry were measured at two positions, providing data for two specific dose rates (about 9 Gy/pulse and 3 Gy/pulse). Maximal beam size was 4cm and 6cm at 90% isodose in the two positions tested. There was no difference between CONV and UHDR mode in the beam characteristics tested.

Conclusions: The device is commissioned for FLASH RT preclinical biological experiments as well as FLASH RT clinical human protocols.
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http://dx.doi.org/10.1002/mp.14885DOI Listing
April 2021

Association of sex differences in dementia risk factors with sex differences in memory decline in a population-based cohort spanning 20-76 years.

Sci Rep 2021 Apr 8;11(1):7710. Epub 2021 Apr 8.

Department of Psychology, University of Alberta, Edmonton, Canada.

Sex differences in late-life memory decline may be explained by sex differences in dementia risk factors. Episodic memory and dementia risk factors were assessed in young, middle-aged and older adults over 12 years in a population-based sample (N = 7485). For men in midlife and old age, physical, cognitive and social activities were associated with less memory decline, and financial hardship was associated with more. APOE e4 and vascular risk factors were associated with memory decline for women in midlife. Depression, cognitive and physical activity were associated with memory change in older women. Incident midlife hypertension (β = - 0.48, 95% CI - 0.87, - 0.09, p = 0.02) was associated with greater memory decline in women and incident late-life stroke accounted for greater memory decline in men (β = - 0.56, 95% CI - 1.12, - 0.01), p = 0.05). Women have fewer modifiable risk factors than men. Stroke and hypertension explained sex differences in memory decline for men and women respectively.
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http://dx.doi.org/10.1038/s41598-021-86397-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032756PMC
April 2021

Societal Need for Interdisciplinary Ageing Research: An International Alliance of Research Universities "Ageing, Longevity and Health" Stream (IARU-ALH) Position Statement.

Biomed Hub 2021 Jan-Apr;6(1):42-47. Epub 2021 Feb 25.

Albertina and Walter Sisulu Institute of Ageing in Africa, University of Cape Town, Cape Town, South Africa.

Ageing is a global concern with major social, health, and economic implications. While individual countries seek to develop responses to immediate, pressing needs, international attention and collaboration is required to most effectively address the multifaceted challenges and opportunities an ageing global population presents in the longer term. The Ageing, Longevity and Health stream of the International Alliance of Research Universities (IARU-ALH) was built on a solid foundation of first-class interdisciplinary research and on innovative outreach and communication centres. This interdisciplinary network conducts projects that span biology, medicine, social sciences, epidemiology, public health, policy, and demography, and actively engages with the public and other societal stakeholders. Here we posit that such international interdisciplinary networks are needed and uniquely placed to address major challenges related to health and ageing and ultimately will produce new understanding and knowledge to promote the awareness of healthy ageing and encourage societal change via novel, science-informed interventions. Global interdisciplinary research presents great potential and opportunities to accelerate our understanding of human ageing and to produce new, more effective solutions to a pressing, complex problem. However, more focused, strategic efforts and investments are required in order to deliver on these potentials and reap maximum benefits for individuals and societies. IARU-ALH members are determined to contribute, in collaboration with others, to delivering on this vision.
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http://dx.doi.org/10.1159/000513513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991603PMC
February 2021

Efficiency of the RADPAD Surgical Cap in Reducing Brain Exposure During Pacemaker and Defibrillator Implantation.

JACC Clin Electrophysiol 2021 02 30;7(2):161-170. Epub 2020 Sep 30.

Department of Cardiology, University Hospital Centre Vaudois, Lausanne, Switzerland. Electronic address:

Objectives: This study sought to investigate the RADPAD No Brainer (Worldwide Innovation and Technologies, Overland Park, Kansas) efficiency in reducing brain exposure to scattered radiation.

Background: Cranial radioprotective caps such as the RADPAD No Brainer are being marketed as devices that significantly reduce operator's brain exposure to scattered radiation. However, the efficiency of the RADPAD No Brainer in reducing brain exposure in clinical practice remains unknown to date.

Methods: Five electrophysiologists performing device implantations over a 2-month period wore the RADPAD cap with 2 strips of 11 thermoluminescent dosimeter pellets covering the front head above and under the shielded cap. Phantom measurements and Monte Carlo simulations were performed to further investigate brain dose distribution.

Results: Our study showed that the right half of the operators' front head was the most exposed region during left subpectoral device implantation; the RADPAD cap attenuated the skin front-head exposure but provided no protection to the brain. The exposure of the anterior part of the brain was decreased by a factor of 4.5 compared with the front-head skin value thanks to the skull. The RADPAD cap worn as a protruding horizontal plane, however, reduced brain exposure by a factor of 1.7 (interquartile range: 1.3 to 1.9).

Conclusions: During device implantation, the RADPAD No Brainer decreased the skin front head exposure but had no impact on brain dose distribution. The RADPAD No Brainer worn as a horizontal plane worn around the neck reduces brain exposure and confirms that the exposure comes from upward scattered radiation.
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http://dx.doi.org/10.1016/j.jacep.2020.08.007DOI Listing
February 2021

Higher Blood Pressure is Associated with Greater White Matter Lesions and Brain Atrophy: A Systematic Review with Meta-Analysis.

J Clin Med 2021 Feb 7;10(4). Epub 2021 Feb 7.

Centre for Research on Ageing, Health and Wellbeing, The Australian National University, Canberra, ACT 2601, Australia.

Background: To summarise and quantify the evidence on the association between Blood pressure (BP), white matter lesions (WMLs), and brain volumes.

Method: Electronic databases PubMed, Scopus, and Clarivate were searched in February 2020 using an established methodology and pre-determined search terms. Studies were eligible for inclusion if they reported on the association between BP and WMLs or brain volume in cognitively healthy individuals, while adjusting for age and intra-cranial volume.

Results: Searches yielded 7509 articles, of which 52 (26 longitudinal and 33 cross-sectional), were eligible and had a combined sample size of 343,794 individuals. Analyses found that 93.7% of studies reported that higher BP was associated with poorer cerebral health (higher WMLs and lower brain volumes). Meta-analysis of compatible results indicated a dose-dependent relationship with every one standard deviation increase in systolic BP (SBP) above 120 mmHg being associated with a 11.2% (95% CI 2.3, 19.9, = 0.0128) increase in WMLs and -0.13% (95% CI -0.25, -0.023, = 0.0183) smaller hippocampal volume.

Conclusion: The association between BP and brain volumes appears across the full range of BP measurements and is not limited to hypertensive individuals. Higher BP in community-residing individuals is associated with poorer cerebral health.
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http://dx.doi.org/10.3390/jcm10040637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915964PMC
February 2021

Corrigendum: The Effect of COVID-19 on Mental Health and Wellbeing in a Representative Sample of Australian Adults.

Front Psychiatry 2020 21;11:619331. Epub 2021 Jan 21.

Centre for Mental Health Research, Research School of Population Health, The Australian National University, Canberra, ACT, Australia.

[This corrects the article DOI: 10.3389/fpsyt.2020.579985.].
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http://dx.doi.org/10.3389/fpsyt.2020.619331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860974PMC
January 2021

Estimating prevalence of subjective cognitive decline in and across international cohort studies of aging: a COSMIC study.

Alzheimers Res Ther 2020 12 18;12(1):167. Epub 2020 Dec 18.

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts.

Methods: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence.

Results: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades.

Conclusions: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.
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http://dx.doi.org/10.1186/s13195-020-00734-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749505PMC
December 2020

The neuroscience of positive emotions and affect: Implications for cultivating happiness and wellbeing.

Neurosci Biobehav Rev 2021 02 8;121:220-249. Epub 2020 Dec 8.

Neuroscience of Cognition and Affection group, Lab of Medical Physics, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece.

This review paper provides an integrative account regarding neurophysiological correlates of positive emotions and affect that cumulatively contribute to the scaffolding for happiness and wellbeing in humans and other animals. This paper reviews the associations among neurotransmitters, hormones, brain networks, and cognitive functions in the context of positive emotions and affect. Consideration of lifespan developmental perspectives are incorporated, and we also examine the impact of healthy social relationships and environmental contexts on the modulation of positive emotions and affect. The neurophysiological processes that implement positive emotions are dynamic and modifiable, and meditative practices as well as flow states that change patterns of brain function and ultimately support wellbeing are also discussed. This review is part of "The Human Affectome Project" (http://neuroqualia.org/background.php), and in order to advance a primary aim of the Human Affectome Project, we also reviewed relevant linguistic dimensions and terminology that characterizes positive emotions and wellbeing. These linguistic dimensions are discussed within the context of the neuroscience literature with the overarching goal of generating novel recommendations for advancing neuroscience research on positive emotions and wellbeing.
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http://dx.doi.org/10.1016/j.neubiorev.2020.12.002DOI Listing
February 2021

Cohort Profile Update: The PATH Through Life Project.

Int J Epidemiol 2021 Mar;50(1):35-36

Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health, Australian National University, Canberra, ACT, Australia.

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http://dx.doi.org/10.1093/ije/dyaa179DOI Listing
March 2021

Longitudinal trajectories of hippocampal volume in middle to older age community dwelling individuals.

Neurobiol Aging 2021 01 21;97:97-105. Epub 2020 Oct 21.

Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health, Australian National University, Canberra, Australian Capital Territory, Australia.

Understanding heterogeneity in brain aging trajectories is important to estimate the extent to which aging outcomes can be optimized. Although brain changes in late life are well-characterized, brain changes in middle age are not well understood. In this study, we investigated hippocampal change in a generally healthy community-living population of middle (n = 421, mean age 47.2 years) and older age (n = 411, mean age 63.0 years) individuals, over a follow-up of up to 12 years. Manually traced hippocampal volumes were analyzed using multilevel models and latent class analysis to investigate longitudinal aging trajectories and laterality and sex effects, and to identify subgroups that follow different aging trajectories. Hippocampal volumes decreased on average by 0.18%/year in middle age and 0.3%/year in older age. Men tended to experience steeper declines than women in middle age only. Three subgroups of individuals following different trajectories were identified in middle age and 2 in older age. Contrary to expectations, the subgroup containing two-thirds of older age participants maintained stable hippocampal volumes across the follow-up.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.10.011DOI Listing
January 2021

The Effect of COVID-19 on Mental Health and Wellbeing in a Representative Sample of Australian Adults.

Front Psychiatry 2020 6;11:579985. Epub 2020 Oct 6.

Centre for Mental Health Research, Research School of Population Health, The Australian National University, Canberra, ACT, Australia.

There is minimal knowledge about the impact of large-scale epidemics on community mental health, particularly during the acute phase. This gap in knowledge means we are critically ill-equipped to support communities as they face the unprecedented COVID-19 pandemic. This study aimed to provide data urgently needed to inform government policy and resource allocation now and in other future crises. The study was the first to survey a representative sample from the Australian population at the early acute phase of the COVID-19 pandemic. Depression, anxiety, and psychological wellbeing were measured with well-validated scales (PHQ-9, GAD-7, WHO-5). Using linear regression, we tested for associations between mental health and exposure to COVID-19, impacts of COVID-19 on work and social functioning, and socio-demographic factors. Depression and anxiety symptoms were substantively elevated relative to usual population data, including for individuals with no existing mental health diagnosis. Exposure to COVID-19 had minimal association with mental health outcomes. Recent exposure to the Australian bushfires was also unrelated to depression and anxiety, although bushfire smoke exposure correlated with reduced psychological wellbeing. In contrast, pandemic-induced impairments in work and social functioning were strongly associated with elevated depression and anxiety symptoms, as well as decreased psychological wellbeing. Financial distress due to the pandemic, rather than job loss , was also a key correlate of poorer mental health. These findings suggest that minimizing disruption to work and social functioning, and increasing access to mental health services in the community, are important policy goals to minimize pandemic-related impacts on mental health and wellbeing. Innovative and creative strategies are needed to meet these community needs while continuing to enact vital public health strategies to control the spread of COVID-19.
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http://dx.doi.org/10.3389/fpsyt.2020.579985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573356PMC
October 2020

Age, menstruation history, and the brain.

Menopause 2020 10 26;28(2):167-174. Epub 2020 Oct 26.

Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health, Australian National University, Florey, Canberra, ACT, Australia.

Objectives: To investigate the cross-sectional association between measures of menstruation history (including menopausal status, age of menopause, age of menarche, and duration of reproductive stage) and brain volume.

Methods: Women (aged 45 to 79 years) from the UK Biobank were included (n = 5,072) after excluding those who had (1) hysterectomy or bilateral oophorectomy, (2) ever used menopausal hormone therapy, (3) ever had a stroke, or (4) were perimenopausal. Multiple linear hierarchical regression models were computed to quantify the cross-sectional association between measures of menstruation history and brain volume. Sensitivity analysis based on propensity matching for age (and other demographic/health covariates) were applied to estimate differences in brain volumes between matched premenopausal and postmenopausal women.

Results: Postmenopausal women had 1.06% (95% confidence interval [CI]; 1.05-1.06) and 2.17% (95% CI, 2.12-2.22) larger total brain volume (TBV) and hippocampal volumes (HV), respectively, than premenopausal women. Sensitivity analysis with age matched samples produced consistent results (TBV: 0.82%, 95% CI, 0.25-1.38; HV: 1.33%, 95% CI, 0.01-2.63). For every year increase in age above 45 years, postmenopausal women experienced 0.23% greater reduction in TBV than premenopausal women (95% CI, -0.60 to -0.14), which was not observed for HV. Moreover, every 1 year delayed onset of menopause after 45 was associated with 0.32% (95% CI, -0.35 to -0.28) and 0.31% (95% CI, -0.40 to -0.22) smaller TBV and HV, respectively. Every additional year in age of menarche was associated with 0.10% (95% CI, 0.04-0.16) larger TBV, which was not detected for HV. Similarly, every 1 year increase in duration of reproductive stage was associated with 0.09% smaller TBV (95% CI, -0.15 to -0.03), which was not detected for HV.

Conclusions: Menopause may contribute to brain volume beyond typical aging effects. Furthermore, early age of menarche, delayed age of menopause and increasing duration of reproductive stage were negatively associated with brain volume. Further research is required to determine whether the negative association between age of menopause and HV is potentially an indicator of future vulnerability for dementia.
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http://dx.doi.org/10.1097/GME.0000000000001688DOI Listing
October 2020

An Internet-Based Intervention Augmented With a Diet and Physical Activity Consultation to Decrease the Risk of Dementia in At-Risk Adults in a Primary Care Setting: Pragmatic Randomized Controlled Trial.

J Med Internet Res 2020 09 24;22(9):e19431. Epub 2020 Sep 24.

Department of General Practice, University of Newcastle, Newcastle, Australia.

Background: There is a need to develop interventions to reduce the risk of dementia in the community by addressing lifestyle factors and chronic diseases over the adult life course.

Objective: This study aims to evaluate a multidomain dementia risk reduction intervention, Body Brain Life in General Practice (BBL-GP), targeting at-risk adults in primary care.

Methods: A pragmatic, parallel, three-arm randomized trial involving 125 adults aged 18 years or older (86/125, 68.8% female) with a BMI of ≥25 kg/m or a chronic health condition recruited from general practices was conducted. The arms included (1) BBL-GP, a web-based intervention augmented with an in-person diet and physical activity consultation; (2) a single clinician-led group, Lifestyle Modification Program (LMP); and (3) a web-based control. The primary outcome was the Australian National University Alzheimer Disease Risk Index Short Form (ANU-ADRI-SF).

Results: Baseline assessments were conducted on 128 participants. A total of 125 participants were randomized to 3 groups (BBL-GP=42, LMP=41, and control=42). At immediate, week 18, week 36, and week 62 follow-ups, the completion rates were 43% (18/42), 57% (24/42), 48% (20/42), and 48% (20/42), respectively, for the BBL-GP group; 71% (29/41), 68% (28/41), 68% (28/41), and 51% (21/41), respectively, for the LMP group; and 62% (26/42), 69% (29/42), 60% (25/42), and 60% (25/42), respectively, for the control group. The primary outcome of the ANU-ADRI-SF score was lower for the BBL-GP group than the control group at all follow-ups. These comparisons were all significant at the 5% level for estimates adjusted for baseline differences (immediate: difference in means -3.86, 95% CI -6.81 to -0.90, P=.01; week 18: difference in means -4.05, 95% CI -6.81 to -1.28, P<.001; week 36: difference in means -4.99, 95% CI -8.04 to -1.94, P<.001; and week 62: difference in means -4.62, 95% CI -7.62 to -1.62, P<.001).

Conclusions: A web-based multidomain dementia risk reduction program augmented with allied health consultations administered within the general practice context can reduce dementia risk exposure for at least 15 months. This study was limited by a small sample size, and replication on a larger sample with longer follow-up will strengthen the results.

Trial Registration: Australian clinical trials registration number (ACTRN): 12616000868482; https://anzctr.org.au/ACTRN12616000868482.aspx.
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http://dx.doi.org/10.2196/19431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545332PMC
September 2020

Lifestyle Risk Factors and Cognitive Outcomes from the Multidomain Dementia Risk Reduction Randomized Controlled Trial, Body Brain Life for Cognitive Decline (BBL-CD).

J Am Geriatr Soc 2020 11 9;68(11):2629-2637. Epub 2020 Sep 9.

Neuroscience Research Australia (NeuRA), Sydney, Australia.

Background/objectives: To evaluate the efficacy of a multidomain intervention to reduce lifestyle risk factors for Alzheimer's disease (AD) and improve cognition in individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI).

Design: The study was an 8-week two-arm single-blind proof-of-concept randomized controlled trial.

Setting: Community-dwelling individuals living in Canberra, Australia, and surrounding areas.

Participants: Participants were 119 individuals (intervention n = 57; control n = 62) experiencing SCD or MCI.

Intervention: The control condition involved four educational modules covering dementia and lifestyle risk factors, Mediterranean diet, physical activity, and cognitive engagement. Participants were instructed to implement this information into their own lifestyle. The intervention condition included the same educational modules and additional active components to assist with the implementation of this information into participants' lifestyles: dietitian sessions, an exercise physiologist session, and online brain training.

Measurements: Lifestyle risk factors for AD were assessed using the Australian National University-Alzheimer's Disease Risk Index (ANU-ADRI), and cognition was assessed using Alzheimer's Disease Assessment Scale-Cognitive subscale, Pfeffer Functional Activities Questionnaire, Symbol Digit Modalities Test (SDMT), Trail Making Test-B, and Category Fluency.

Results: The primary analysis showed that the intervention group had a significantly lower ANU-ADRI score (χ = 10.84; df = 3; P = .013) and a significantly higher cognition score (χ = 7.28; df = 2; P = .026) than the control group. A secondary analysis demonstrated that the changes in lifestyle were driven by increases in protective lifestyle factors (χ = 12.02; df = 3; P = .007), rather than a reduction in risk factors (χ = 2.93; df = 3; P = .403), and cognitive changes were only apparent for the SDMT (χ = 6.46; df = 2; P = .040). Results were robust to intention-to-treat analysis controlling for missing data.

Conclusion: Results support the hypothesis that improvements in lifestyle risk factors for dementia can lead to improvements in cognition over a short time frame with a population experiencing cognitive decline. Outcomes from this trial support the conduct of a larger and longer trial with this participant group.
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http://dx.doi.org/10.1111/jgs.16762DOI Listing
November 2020

Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment.

Arch Gerontol Geriatr 2020 Nov/Dec;91:104112. Epub 2020 Jul 13.

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

Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).

Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.

Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers.

Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.
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http://dx.doi.org/10.1016/j.archger.2020.104112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724926PMC
December 2020

Volumetric brain differences in clinical depression in association with anxiety: a systematic review with meta-analysis.

J Psychiatry Neurosci 2020 11;45(6):406-429

From the Centre for Research on Ageing, Health and Wellbeing, The Australian National University, Canberra, ACT, Australia (Espinoza Oyarce, Alateeq, Cherbuin); and the College of Engineering and Computer Science, The Australian National University, Canberra, ACT, Australia (Shaw).

Background: Structural differences associated with depression have not been confirmed in brain regions apart from the hippocampus. Comorbid anxiety has been inconsistently assessed, and may explain discrepancies in previous findings. We investigated the link between depression, comorbid anxiety and brain structure.

Methods: We followed Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42018089286). We searched the Cochrane Library, MEDLINE, PsycInfo, PubMed and Scopus, from database inception to Sept. 13, 2018, for MRI case-control studies that reported brain volumes in healthy adults and adults with clinical depression. We summarized mean volumetric differences using meta-analyses, and we assessed demographics, depression factors and segmentation procedure as moderators using meta-regressions.

Results: We included 112 studies in the meta-analyses, assessing 4911 healthy participants and 5934 participants with depression (mean age 49.8 yr, 68.2% female). Volume effects were greater in late-onset depression and in multiple episodes of depression. Adults with depression and no comorbidity showed significantly lower volumes in the putamen, pallidum and thalamus, as well as significantly lower grey matter volume and intracranial volume; the largest effects were in the hippocampus (6.8%, p < 0.001). Adults with depression and comorbid anxiety showed significantly higher volumes in the amygdala (3.6%, p < 0.001). Comorbid anxiety lowered depression effects by 3% on average. Sex moderated reductions in intracranial volume.

Limitations: High heterogeneity in hippocampus effects could not be accounted for by any moderator. Data on symptom severity and medication were sparse, but other factors likely made significant contributions.

Conclusion: Depression-related differences in brain structure were modulated by comorbid anxiety, chronicity of symptoms and onset of illness. Early diagnosis of anxiety symptomatology will prove crucial to ensuring effective, tailored treatments for improving long-term mental health and mitigating cognitive problems, given the effects in the hippocampus.
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http://dx.doi.org/10.1503/jpn.190156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595741PMC
November 2020

Objectively measured physical activity is associated with dorsolateral prefrontal cortex volume in older adults.

Neuroimage 2020 11 12;221:117150. Epub 2020 Jul 12.

Centre for Research on Ageing, Health and Wellbeing, Australian National University, ACT, 2601, Australia.

Background: Epidemiological studies suggest physical activity (PA) can slow or prevent both cognitive decline and age-related atrophy in frontal and hippocampal gray matter volumes. However, much of this evidence is based on self-reported measures of PA.

Methods: PA was measured objectively with a SenseWear™ Armband to examine the cross-sectional associations between the duration of light, moderate and vigorous intensity PA with gray matter volume in the dorsolateral prefrontal cortex (DLPFC) and hippocampus in 167 (female: 43%) cognitively healthy older adults aged 73 to 78.

Results: The duration of objective moderate to vigorous intensity physical activity (MVPA) was associated with a greater volume of the right DLPFC (β ​= ​0.16; p ​= ​0.04). In addition, objective moderate-intensity PA alone was also associated with greater volume of the left (β ​= ​0.17; p ​= ​0.03) and right (β ​= ​0.19; p ​= ​0.01) DLPFC after controlling for covariates and adjustment for multiple comparisons. In contrast, there were no significant associations between light- or vigorous-intensity PA and gray matter volumes (all p ​> ​0.05). No associations between PA and cognitive performance were detected, and self-reported PA was not associated with any of the outcomes investigated.

Conclusions: These findings suggest that an intensity-dependent relationship may exist, whereby a greater duration of MVPA, perhaps driven by moderate-intensity PA, is associated with preserved gray matter volume in frontal regions of the brain. Future research should investigate the mechanisms of this dose-effect and determine whether greater brain volumes associated with objective PA convey protective effects against cognitive decline.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117150DOI Listing
November 2020

Midlife susceptibility to the effects of poor diet on diabetes risk.

Eur J Clin Nutr 2021 Jan 10;75(1):85-90. Epub 2020 Jul 10.

Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, ACT, Australia.

Objective: Type 2 diabetes mellitus (T2D) prevalence continues to increase, and age of incidence continues to decrease. More information is needed to target interventions to the ages where they can be most effective. The objective of this study was to explore the degree to which the association between diet and T2D incidence changes through adulthood.

Methods: Participants were a large number (N = 2818) of community living adults in Canberra and Queanbeyan, Australia across three cohorts; young (20-24 followed to 32-36), mid-life (40-44 followed to 52-56) and late-life (60-64 followed to 72-76). Self-report dietary pattern scores at baseline and diabetes incidence across 12 years follow-up were measured, alongside confounders of caloric intake, sex, smoking status, years of education, hypertension, BMI and physical activity.

Results: Cox proportional hazards indicated that neither Western nor Prudent dietary pattern scores were significantly associated with T2D incidence when confounders were included in the model. Unadjusted estimates suggested a positive association between Western dietary pattern scores and subsequent diabetes incidence (HR = 1.40, 95% CI [1.18, 1.64]). Compared with the mid-life cohort, a higher Western dietary pattern score posed a lower risk for incident T2D in the young cohort (unadjusted HR = 0.46, 95% CI [0.22, 0.96]), who also had significantly lower BMI and higher physical activity. No such significant effects were found for the late-life cohort.

Conclusions: Our findings indicate that mid-life may be a period of heightened vulnerability to the effects of an unhealthy diet on diabetes risk, but this effect is attenuated when risk factors related to diet, such as adiposity, are taken into account.
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http://dx.doi.org/10.1038/s41430-020-0673-9DOI Listing
January 2021

Speaking of aging: Changes in gray matter asymmetry in Broca's area in later adulthood.

Cortex 2020 08 24;129:133-140. Epub 2020 Apr 24.

School of Psychology, University of Auckland, Auckland, New Zealand; Centre for Research on Ageing Health and Wellbeing, Australian National University, Canberra, Australia.

Several theories suggest a change in the brain's asymmetry as we get older. However, it is currently unresolved whether Broca's area, consisting of left Brodmann Areas (BA) 45 and 44, undergoes age-related changes. To address this question, we mapped associations between chronological age and gray matter asymmetry of BA45 and BA44 in a large sample (n = 485) of adults ranging between 42 and 97 years of age. Hemisphere-specific gray matter volumes and asymmetry indices were obtained by integrating cytoarchitectonic probabilities with MRI-based signal intensities. For BA44, we did not observe any significant correlation between age and gray matter asymmetry. In contrast, for BA45, the analysis revealed a significant correlation, which indicates a decreasing asymmetry from rightward to less rightward with increasing age. A subsequent characterization of hemisphere-specific volume loss revealed significant negative associations between age and gray matter volume for left and right BA45, but with weaker effects in the left hemisphere compared to the right. These findings seem to support the assumption of reduced structural asymmetries later in life, at least for BA45, which seem to be driven by a stronger tissue loss in the right hemisphere than the left hemisphere.
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http://dx.doi.org/10.1016/j.cortex.2020.03.028DOI Listing
August 2020

Longitudinal Changes in Fat Mass and the Hippocampus.

Obesity (Silver Spring) 2020 07 19;28(7):1263-1269. Epub 2020 May 19.

Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health, The Australian National University, Canberra, Australia.

Objective: This study aimed to investigate cross-sectional and longitudinal associations between fat mass (i.e., body mass index [BMI], waist circumference [WC], and waist to hip ratio [WTHR]) and hippocampal volumes.

Methods: UK Biobank participants (N = 20,395) aged 40 to 70 years (mean follow-up = 7.66 years), were included and categorized into one of four groups, which represented their baseline fat mass status and trajectory of change by follow-up assessment: normal weight to overweight/obesity, overweight/obesity to normal weight (ON), normal weight stable (NS), or overweight/obesity stable (OS). Regression models used NS (WC < 80 cm in women and < 94 cm in men; WTHR < 0.85 in women and < 0.90 in men; BMI < 25 kg/m in women and men) as the reference group. Hippocampal volumes were automatically segmented using the FMRIB Software Library.

Results: Compared with NS, OS (BMI: B = -62.23 [SE = 16.76]; WC: B = -145.56 [SE = 16.97]; WTHR: B = -101.26 [SE = 19.54]) and ON (BMI: B = -61.1 [SE = 30.3]; WC: B = -93.77 [SE = 24.96]; WTHR: B = -69.92 [SE = 26.22]) had significantly lower hippocampal volumes.

Conclusions: The detrimental effects of overweight/obesity may extend beyond the duration of overweight/obesity itself.
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http://dx.doi.org/10.1002/oby.22819DOI Listing
July 2020

APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline.

J Gerontol A Biol Sci Med Sci 2020 09;75(10):1863-1873

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

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.
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http://dx.doi.org/10.1093/gerona/glaa116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518559PMC
September 2020

Role of apolipoprotein E epsilon 4 (*ε4) as an independent risk factor for incident depression over a 12-year period in cognitively intact adults across the lifespan.

BJPsych Open 2020 May 8;6(3):e47. Epub 2020 May 8.

School of Psychology, University of New South Wales, Australia; and Neuroscience Research Australia, Australia.

Background: The apolipoprotein E ε4 allele (APOE*ε4) is indicated as a risk for Alzheimer's disease and other age-related diseases. The risk attributable to APOE*ε4 for depression is less clear and may be because of confounding of the relationship between dementia and depression.

Aims: We examined the risk of APOE* ε4 for incident depression and depressive symptomology over a 12-year period across the adult lifespan.

Method: Participants were from the Personality and Total Health Through Life study, aged 20 to 24 (n = 1420), 40 to 44 (n = 1592) or 60-64 (n = 1768) at baseline, and interviewed every 4 years since 1999. Ethnicities other than White, those without genotyping and those with depression at baseline, or who reported strokes and scores on the Mini-Mental State Examination <27 at any observation, were excluded.

Results: Over the study period, there was no evidence that APOE*ε4+ was a risk factor for depression, including any depression (odds ratio (OR) = 0.94, 95% CI 0.77-1.16, P = 0.573), major depression (OR = 0.96, 95% CI 0.60-1.53, P = 0.860), minor depression (OR = 0.94, 95% CI 0.67-1.30, P = 0.695) or depressive symptomology (incidence rate ratio (IRR) = 1.02, 95% CI 0.97-1.08, P = 0.451). APOE*ε4 was unrelated to incident depression. Findings were consistent for all age cohorts.

Conclusions: Among cognitively intact Australian adults who were free of depression at baseline, there was little evidence that APOE*ε4+ carriers are at increased risk for depression over a 12-year period among those who are cognitively intact.
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http://dx.doi.org/10.1192/bjo.2020.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331079PMC
May 2020

Experts' perceptions on the use of visual analytics for complex mental healthcare planning: an exploratory study.

BMC Med Res Methodol 2020 05 7;20(1):110. Epub 2020 May 7.

Centre for Mental Health Research, Research School of Population Health, College of Health and Medicine, Australian National University, 63 Eggleston Road, Acton, ACT, 2601, Australia.

Background: Health experts including planners and policy-makers face complex decisions in diverse and constantly changing healthcare systems. Visual analytics may play a critical role in supporting analysis of complex healthcare data and decision-making. The purpose of this study was to examine the real-world experience that experts in mental healthcare planning have with visual analytics tools, investigate how well current visualisation techniques meet their needs, and suggest priorities for the future development of visual analytics tools of practical benefit to mental healthcare policy and decision-making.

Methods: Health expert experience was assessed by an online exploratory survey consisting of a mix of multiple choice and open-ended questions. Health experts were sampled from an international pool of policy-makers, health agency directors, and researchers with extensive and direct experience of using visual analytics tools for complex mental healthcare systems planning. We invited them to the survey, and the experts' responses were analysed using statistical and text mining approaches.

Results: The forty respondents who took part in the study recognised the complexity of healthcare systems data, but had most experience with and preference for relatively simple and familiar visualisations such as bar charts, scatter plots, and geographical maps. Sixty-five percent rated visual analytics as important to their field for evidence-informed decision-making processes. Fifty-five percent indicated that more advanced visual analytics tools were needed for their data analysis, and 67.5% stated their willingness to learn new tools. This was reflected in text mining and qualitative synthesis of open-ended responses.

Conclusions: This exploratory research provides readers with the first self-report insight into expert experience with visual analytics in mental healthcare systems research and policy. In spite of the awareness of their importance for complex healthcare planning, the majority of experts use simple, readily available visualisation tools. We conclude that co-creation and co-development strategies will be required to support advanced visual analytics tools and skills, which will become essential in the future of healthcare.
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http://dx.doi.org/10.1186/s12874-020-00986-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206783PMC
May 2020

Towards an understanding of the physical activity-BDNF-cognition triumvirate: A review of associations and dosage.

Ageing Res Rev 2020 07 13;60:101044. Epub 2020 Mar 13.

Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health, 54 Mills Road, Australian National University, Acton, ACT, 2615, Australia. Electronic address:

Physical activity has received substantial research attention due to its beneficial impact on cognition in ageing, particularly via the action of brain-derived neurotrophic factor (BDNF). It is well established that physical activity can elevate circulating levels of BDNF, and that BDNF has neurotrophic, neuroprotective and cognitively beneficial properties. Yet, practical implementation of this knowledge is limited by a lack of clarity on context and dose-effect. Against a shifting backdrop of gradually diminishing physical and cognitive capacity in normal ageing, the type, intensity, and duration of physical activity required to elicit elevations in BDNF, and more importantly, the magnitude of BDNF elevation required for detectable neuroprotection remains poorly characterised. The purpose of this review is to provide an overview of the association between physical activity, BDNF, and cognition, with a focus on clarifying the magnitude of these effects in the context of normative ageing. We discuss the implications of the available evidence for the design of physical activity interventions intended to promote healthy cognitive ageing.
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http://dx.doi.org/10.1016/j.arr.2020.101044DOI Listing
July 2020

Regional brain atrophy predicts time to conversion to Alzheimer's disease, dependent on baseline volume.

Neurobiol Aging 2019 11 10;83:86-94. Epub 2019 Sep 10.

Centre for Research on Ageing, Health and Wellbeing, The Australian National University, Canberra, Australia.

A key question for the design of clinical trials for Alzheimer's disease (AD) is whether the timing of conversion from mild cognitive impairment (MCI) to AD can be predicted. This is also an important question for the clinical management of MCI. This study aims to address this question by exploring the contribution of baseline brain volume and annual volume change, using Cox regression, in predicting the time to conversion. Individuals with MCI, who converted to AD (n = 198), reverted to normal (n = 38), or remained stable (n = 96) for at least five years, were included in this study. The results revealed that the volumes of all the brain areas considered were predictive of the time to conversion from MCI to AD. Annual change in volume was also predictive of the time to conversion but only when initial volumes were above a certain threshold. This is important because it suggests that reduction in atrophy rate, which is the outcome of some clinical trials, is not inevitably associated with delay in conversion from MCI to AD.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.08.033DOI Listing
November 2019

Lipid profile differences during menopause: a review with meta-analysis.

Menopause 2019 11;26(11):1327-1333

Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health, Australian National University, Canberra, Australia.

Objectives: The aim of the study was to determine lipid profile differences between premenopausal and postmenopausal women.

Methods: The present review used a meta-analytic approach. Sixty-six studies were included, which provided a total sample of 114,655 women consisting of 68,394 that were premenopausal and 46,261 that were postmenopausal.

Results: The main findings were that (1) lipoproteins were significantly higher in postmenopausal women compared to premenopausal women including triglycerides (0.27 mmol/L, 95% confidence interval, 0.22-0.31), total cholesterol (0.58, 0.50-0.65), low-density lipoprotein (0.45, 0.38-0.53), and total cholesterol to high-density lipoprotein levels (0.39, 0.16-0.62); (2) there was no difference in high-density lipoprotein levels between premenopausal and postmenopausal women (0.02, -0.00-0.04); and (3) the differences in lipid levels was partly attributable to the mean age difference between premenopausal and postmenopausal women.

Conclusions: These findings are important as they provide precise estimates of lipid differences in women around menopause. Furthermore the results suggest that the unfavorable lipid profile that develops in postmenopausal women puts them at higher risk of cardiovascular disease such as heart disease and stroke if appropriate lifestyle/pharmacological interventions are not implemented.
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http://dx.doi.org/10.1097/GME.0000000000001403DOI Listing
November 2019

The Association of Sedentary Behaviour and Cognitive Function in People Without Dementia: A Coordinated Analysis Across Five Cohort Studies from COSMIC.

Sports Med 2020 Feb;50(2):403-413

Department of Geriatrics/Radboud Alzheimer Center, Radboud Institute for Health Sciences, Radboud University Medical Center, Route 925, Postbus 9101, 6500 HB, Nijmegen, The Netherlands.

Background: Besides physical activity as a target for dementia prevention, sedentary behaviour is hypothesized to be a potential target in its own right. The rising number of persons with dementia and lack of any effective treatment highlight the urgency to better understand these modifiable risk factors. Therefore, we aimed to investigate whether higher levels of sedentary behaviour are associated with reduced global cognitive functioning and slower cognitive decline in older persons without dementia.

Methods: We used five population cohorts from Greece, Australia, USA, Japan, and Singapore (HELIAD, PATH, SALSA, SGS, and SLAS2) from the Cohort Studies of Memory in an International Consortium. In a coordinated analysis, we assessed the relationship between sedentary behaviour and global cognitive function with the use of linear mixed growth model analysis (mean follow-up range of 2.0-8.1 years).

Results: Baseline datasets combined 10,450 older adults without dementia with a mean age range between cohorts of 66.7-75.1 years. After adjusting for multiple covariates, no cross-sectional association between sedentary behaviour and cognition was found in four studies. One association was detected where more sedentary behaviour was cross-sectionally linked to higher cognition levels (SLAS2, B = 0.118 (0.075; 0.160), P < 0.001). Longitudinally, there were no associations between baseline sedentary behaviour and cognitive decline (P > 0.05).

Conclusions: Overall, these results do not suggest an association between total sedentary time and lower global cognition in older persons without dementia at baseline or over time. We hypothesize that specific types of sedentary behaviour may differentially influence cognition which should be investigated further. For now, it is, however, too early to establish undifferentiated sedentary time as a potential effective target for minimizing cognitive decline in older adults without dementia.
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http://dx.doi.org/10.1007/s40279-019-01186-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985182PMC
February 2020

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

PLoS Med 2019 07 23;16(7):e1002853. Epub 2019 Jul 23.

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

Background: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.

Methods And Findings: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife.

Conclusions: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.
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http://dx.doi.org/10.1371/journal.pmed.1002853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650056PMC
July 2019