Publications by authors named "Joanne Ryan"

140 Publications

Similar mortality risk in incident cognitive impairment and dementia: Evidence from the ASPirin in Reducing Events in the Elderly (ASPREE) trial.

J Am Geriatr Soc 2021 Sep 17. Epub 2021 Sep 17.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Background: This study examined the risk of mortality in older adults with newly detected cognitive impairment or dementia.

Methods: Data from the Australian cohort of the ASPirin in Reducing Events in the Elderly (ASPREE) trial were examined. The ASPREE clinical trial compared daily low-dose aspirin to a placebo and involved 16,703 individuals aged 70 years and over, who were without major cognitive impairment, physical disability, or cardiovascular disease at recruitment. During the trial, evidence of cognitive impairment, based on cognitive testing and medical record information, triggered dementia adjudication of participants using DSM-IV criteria. Cox proportional hazard models were used to compare mortality rates across the dementia, trigger-only, and no-trigger groups.

Results: Over a median 4.7-year follow-up period, 806 participants triggered dementia adjudication, with 485 (60.2%) judged to have dementia. Following recruitment, mortality risks were 32.9, 33.6, and 10.8 events per 1000 person-years in the dementia, trigger-no-dementia, and no-trigger groups, respectively. In the fully adjusted model, mortality risks remained higher in the dementia and trigger-no-dementia groups, with hazard ratios of 1.7 (95% CI: 1.3-2.1) and 1.9 (95% CI: 1.5-2.6), respectively. There was no discernible difference between the dementia and trigger-no-dementia groups in mortality rates following recruitment, or following a dementia trigger. These two groups were more likely to die from sepsis, respiratory disease, and dementia, but less likely to die from cancer than the no-trigger group, χ  = 161.5, p < 0.001.

Conclusion: ASPREE participants who triggered for a dementia evaluation experienced a substantially higher mortality rate than those who remained cognitively intact. The increase was indistinguishable among persons who met DSM-IV criteria for dementia vs. those who triggered for a dementia evaluation but failed to meet DSM-IV criteria. Future work should investigate whether earlier detection of cognitive decline can be used to identify and prevent early mortality.
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http://dx.doi.org/10.1111/jgs.17435DOI Listing
September 2021

Longitudinal prediction of periconception alcohol use: a 20-year prospective cohort study across adolescence, young adulthood and pregnancy.

Addiction 2021 Sep 8. Epub 2021 Sep 8.

Murdoch Children's Research Institute, Melbourne, VIC, Australia.

Background And Aims: Alcohol consumption is common in adolescence and young adulthood and may continue into pregnancy, posing serious risk to early fetal development. We examine the frequency of periconception alcohol use (prior to pregnancy awareness) and the extent to which adolescent and young adult alcohol use prospectively predict periconception use.

Design: A longitudinal, population-based study.

Setting: Victoria, Australia.

Participants: A total of 289 women in trimester three of pregnancy (age 29-35 years; 388 pregnancies).

Measures: The main exposures were binge [≥ 4.0 standard drinks (SDs)/day] and frequent (≥ 3 days/week) drinking in adolescence (mean age = 14.9-17.4 years) and young adulthood (mean age 20.7-29.1 years). Outcomes were frequency (≥ 3 days/week, ≥ monthly, never) and quantity (≥ 4.0 SDs, ≥ 0.5 and < 4.0 SDs, none) of periconception drinking.

Findings: Alcohol use was common in young adulthood prior to pregnancy (72%) and in the early weeks of pregnancy (76%). The proportions drinking on most days and binge drinking were similar at both points. Reflecting a high degree of continuity in alcohol use behaviours, most women who drank periconceptionally had an earlier history of frequent (77%) and/or binge (85%) drinking throughout the adolescent or young adult years. Young adult binge drinking prospectively predicted periconception drinking quantity [odds ratio (OR) = 3.7, 95% confidence interval (CI) = 1.9-7.4], compared with women with no prior history. Similarly, frequent young adult drinking prospectively predicted frequent periconception drinking (OR = 30.7, 95% CI = 12.3-76.7).

Conclusions: Women who engage in risky (i.e. frequent and binge) drinking in their adolescent and young adult years are more likely to report risky drinking in early pregnancy prior to pregnancy recognition than women with no prior history of risky drinking.
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http://dx.doi.org/10.1111/add.15632DOI Listing
September 2021

Polygenic score modifies risk for Alzheimer's disease in ε4 homozygotes at phenotypic extremes.

Alzheimers Dement (Amst) 2021 5;13(1):e12226. Epub 2021 Aug 5.

Department of Epidemiology and Preventive Medicine School of Public Health and Preventive Medicine Monash University Melbourne Australia.

Introduction: Diversity in cognition among apolipoprotein E () ε4 homozygotes can range from early-onset Alzheimer's disease (AD) to a lifetime with no symptoms.

Methods: We evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy ε4 homozygotes aged ≥75 years (n = 213) and early-onset ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity.

Results: The PRS for AD was significantly higher in ε4 homozygote AD cases compared to older cognitively healthy ε4/ε4 controls (odds ratio [OR] 8.39; confidence interval [CI] 2.0-35.2;  = .003). The difference in the same PRS between ε3/ε3 extremes was not as significant (OR 3.13; CI 0.98-9.92;  = .053) despite similar numbers and power. There was no statistical difference in an educational attainment PRS between these age extreme case-controls.

Discussion: A PRS for AD contributes to modified cognitive expression of the ε4/ε4 genotype at phenotypic extremes of risk.
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http://dx.doi.org/10.1002/dad2.12226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339682PMC
August 2021

Factors associated with brain ageing - a systematic review.

BMC Neurol 2021 Aug 12;21(1):312. Epub 2021 Aug 12.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, 3004, Australia.

Background: Brain age is a biomarker that predicts chronological age using neuroimaging features. Deviations of this predicted age from chronological age is considered a sign of age-related brain changes, or commonly referred to as brain ageing. The aim of this systematic review is to identify and synthesize the evidence for an association between lifestyle, health factors and diseases in adult populations, with brain ageing.

Methods: This systematic review was undertaken in accordance with the PRISMA guidelines. A systematic search of Embase and Medline was conducted to identify relevant articles using search terms relating to the prediction of age from neuroimaging data or brain ageing. The tables of two recent review papers on brain ageing were also examined to identify additional articles. Studies were limited to adult humans (aged 18 years and above), from clinical or general populations. Exposures and study design of all types were also considered eligible.

Results: A systematic search identified 52 studies, which examined brain ageing in clinical and community dwelling adults (mean age between 21 to 78 years, ~ 37% were female). Most research came from studies of individuals diagnosed with schizophrenia or Alzheimer's disease, or healthy populations that were assessed cognitively. From these studies, psychiatric and neurologic diseases were most commonly associated with accelerated brain ageing, though not all studies drew the same conclusions. Evidence for all other exposures is nascent, and relatively inconsistent. Heterogenous methodologies, or methods of outcome ascertainment, were partly accountable.

Conclusion: This systematic review summarised the current evidence for an association between genetic, lifestyle, health, or diseases and brain ageing. Overall there is good evidence to suggest schizophrenia and Alzheimer's disease are associated with accelerated brain ageing. Evidence for all other exposures was mixed or limited. This was mostly due to a lack of independent replication, and inconsistency across studies that were primarily cross sectional in nature. Future research efforts should focus on replicating current findings, using prospective datasets.

Trial Registration: A copy of the review protocol can be accessed through PROSPERO, registration number CRD42020142817 .
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http://dx.doi.org/10.1186/s12883-021-02331-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359541PMC
August 2021

Validation of a deficit-accumulation Frailty Index in the ASPREE study and its predictive capacity for disability-free survival.

J Gerontol A Biol Sci Med Sci 2021 Aug 2. Epub 2021 Aug 2.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria Australia.

Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterise a 67-item deficit-accumulation frailty index (FI) in 19,110 community-dwelling individuals in the ASPREE clinical trial. Participants aged 65 to 98 years were recruited from the U.S. and Australia, and were without diagnosed dementia and cardiovascular disease, and without major physical disability. The median FI score was 0.10 (IQR: 0.07; 0.14) at baseline, and the prevalence of frailty (FI> 0.21) increased from 8.1% to 17.4% after six years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r =-0.31) and grip strength (r = -0.46), and strongly associated with a modified Fried frailty phenotype (p<0.0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (HR:21.3, 95% CI:15.6-28.9). It added significantly to the predictive capacity of these outcomes above age, sex and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals, and provides important information about an individual's vulnerability to and risk of disease.
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http://dx.doi.org/10.1093/gerona/glab225DOI Listing
August 2021

Dispositional Optimism and All-Cause Mortality in Older Adults: A Cohort Study.

Psychosom Med 2021 Oct;83(8):938-945

From the School of Public Health and Preventive Medicine (Craig, Ryan, Freak-Poli, Owen, McNeil, Woods, Ward, Britt, Gasevic), Monash University, Melbourne, Victoria, Australia; Department of Epidemiology (Freak-Poli), Erasmus Medical Centre, Rotterdam, the Netherlands; PSNREC, Univ Montpellier, INSERM (Ryan), Montpellier, France; and Usher Institute (Gasevic), University of Edinburgh, Edinburgh, United Kingdom.

Objective: Optimism is modifiable and may be associated with healthy aging. We aim to investigate whether dispositional optimism is associated with all-cause mortality in adults 70 years and older.

Methods: Between 2010 and 2014, older adults free of serious cardiovascular disease and dementia were recruited through primary care physicians and enrolled in the Aspirin Reducing Events in the Elderly (ASPREE) clinical trial. Australian ASPREE participants were invited to participate in the ASPREE Longitudinal Study of Older Persons (ALSOP) that was running in parallel to ASPREE. Optimism was assessed at baseline using the Life Orientation Test-Revised. The association between optimism, divided into quartiles, and all-cause mortality was assessed using Cox proportional hazards models.

Results: A total of 11,701 participants (mean [standard deviation] age = 75.1 [4.24] years; 46.6% men) returned the ALSOP Social questionnaire and completed the Life Orientation Test-Revised. During a median follow-up of 4.7 years, 469 deaths occurred. The fully adjusted model was not significant (hazard ratio = 0.78, 95% confidence interval = 0.58-1.06). There was evidence that age was an effect modifier of the association between optimism and longevity. Higher optimism was associated with lower mortality risk in the oldest individuals only (77+ years; hazard ratio = 0.61, 95% confidence interval = 0.39-0.96).

Conclusions: We observed no independent relationship between optimism and all-cause mortality in the total sample, although optimism seemed to be associated with lower risk among the oldest old (adults 77 years and older).
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http://dx.doi.org/10.1097/PSY.0000000000000989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490272PMC
October 2021

Health-related quality of life and incident cardiovascular disease events in community-dwelling older people: A prospective cohort study.

Int J Cardiol 2021 09 7;339:170-178. Epub 2021 Jul 7.

School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia; Department of Epidemiology, Erasmus Medical Centre, 3015 GD Rotterdam, The Netherlands. Electronic address:

Background: Lower health-related quality of life (HRQoL) has been shown to predict a higher risk of hospital readmission and mortality in patients with cardiovascular disease (CVD). Few studies have explored the associations between HRQoL and incident CVD. We explored the associations between baseline HRQoL and incident and fatal CVD in community-dwelling older people in Australia and the United States.

Methods: Longitudinal study using ASPirin in Reducing Events in the Elderly (ASPREE) trial data. This includes 19,106 individuals aged 65-98 years, initially free of CVD, dementia, or disability, and followed between March 2010 and June 2017. The physical (PCS) and mental component scores (MCS) of HRQoL were assessed using the SF-12 questionnaire. Incident major adverse CVD events included fatal CVD (death due to atherothrombotic CVD), hospitalizations for heart failure, myocardial infarction or stroke. Analyses were performed using Cox proportional-hazard regression.

Results: Over a median 4.7 follow-up years, there were 922 incident CVD events, 203 fatal CVD events, 171 hospitalizations for heart failure, 355 fatal or nonfatal myocardial infarction and 403 fatal or nonfatal strokes. After adjustment for sociodemographic, health-related behaviours and clinical measures, a 10-unit higher PCS, but not MCS, was associated with a 14% lower risk of incident CVD, 28% lower risk of hospitalization for heart failure and 15% lower risk of myocardial infarction. Neither PCS nor MCS was associated with fatal CVD events or stroke.

Conclusion: Physical HRQoL can be used in combination with clinical data to identify the incident CVD risk among older individuals.
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http://dx.doi.org/10.1016/j.ijcard.2021.07.004DOI Listing
September 2021

Social isolation, social support, loneliness and cardiovascular disease risk factors: A cross-sectional study among older adults.

Int J Geriatr Psychiatry 2021 Nov 21;36(11):1795-1809. Epub 2021 Jul 21.

Department of Epidemiology and Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia.

Background: Social health reflects one's ability to form interpersonal relationships. Poor social health is a risk factor for cardiovascular disease (CVD), however an in-depth exploration of the link through CVD risk factors is lacking.

Aim: To examine the relationship between social health (social isolation, social support, loneliness) and CVD risk factors among healthy older women and men.

Methods: Data were from 11,498 healthy community-dwelling Australians aged ≥70 years from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and the ASPREE Longitudinal Study of Older Persons sub-study. Ten-year CVD risk was estimated using the Atherosclerotic CVD Risk Scale (ASCVDRS) and the Framingham Risk Score (FRS).

Results: Physical inactivity and experiencing depressive symptoms were the only CVD risk factors that consistently differed by all three social health constructs. Loneliness was associated with greater ASCVDRS (women: β = 0.01, p < 0.05; men: β = 0.03, p < 0.001), social isolation with greater FRS (women: β = 0.02, p < 0.01; men: β = 0.03, p < 0.01) and the social health composite of being lonely (regardless of social isolation and/or social support status) with greater ASCVDRS (women: β = 0.01, p = 0.02; men: β = 0.03, p < 0.001). Among men, loneliness was also associated with greater FRS (β = 0.03, p < 0.001) and social support with greater ASCVDRS (β = 0.02, p = 0.01). Men were more socially isolated, less socially supported and less lonely than women.

Conclusion: Social isolation, social support and loneliness displayed diverse relationships with CVD risk factors and risk scores, emphasising the importance of distinguishing between these constructs. These findings inform on potential avenues to manage poor social health and CVD risk among older adults.
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http://dx.doi.org/10.1002/gps.5601DOI Listing
November 2021

Social isolation, social support and loneliness as independent concepts, and their relationship with health-related quality of life among older women.

Aging Ment Health 2021 Jul 5:1-10. Epub 2021 Jul 5.

Research Centre for Generational Health and Ageing, University of Newcastle, Newcastle, Australia.

To assess whether social isolation, social support, and loneliness are independently associated with health-related quality of life (HRQoL). Retrospective analysis including 10,517 women aged 70-75 years from the Australian Longitudinal Study on Women's Health (ALSWH). Social isolation, social support (Duke Social Support Index), and loneliness (single item) were investigated for their association with standardised HRQoL (physical [PCS] and mental [MCS] components of the SF-36® questionnaire). Analyses were adjusted for sociodemographic variables and number of medical conditions. Only 3% reported being socially isolated, having low social support and being lonely, and 34% reported being not socially isolated, high social support and not being lonely. Each construct was independently associated with HRQoL, with loneliness having the strongest inverse association (PCS: isolation -0.98, low support -2.01, loneliness -2.03; MCS: isolation -1.97, low support -4.79, loneliness -10.20; p-value < 0.001 for each). Women who were not isolated or lonely and with high social support had the greatest HRQoL (compared to isolated, low social support and lonely; MCS: 17 to 18 points higher, PCS: 5 to 8 points higher). Other combinations of social isolation, social support and loneliness varied in their associations with HRQoL. Ageing populations face the challenge of supporting older people to maintain longer, healthy, meaningful and community-dwelling lives. Among older women, social isolation, low social support and loneliness are distinct, partially overlapping yet interconnected concepts that coexist and are each adversely associated with HRQoL. Findings should be replicated in other cohorts to ensure generalisability across other age groups and men.
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http://dx.doi.org/10.1080/13607863.2021.1940097DOI Listing
July 2021

Long-Term Blood Pressure Variability and Risk of Cognitive Decline and Dementia Among Older Adults.

J Am Heart Assoc 2021 07 26;10(13):e019613. Epub 2021 Jun 26.

Berman Center for Outcomes and Clinical Research Hennepin-Health Research InstituteHennepin Healthcare Minneapolis MN.

Background Blood pressure variability (BPV) in midlife increases risk of late-life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long-term, visit-to-visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. Methods and Results ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow-up visits. Time-to-event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. Individuals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction =0.02), with increased risk in men (HR, 1.68; 95% CI, 1.19-2.39) but not women (HR, 1.01; 95% CI, 0.72-1.42). For cognitive decline, similar increased risks were observed for men and women (interaction =0.15; men: HR, 1.36; 95% CI, 1.16-1.59; women: HR, 1.14; 95% CI, 0.98-1.32). Conclusions High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583; isrctn.com. Identifier: ISRCTN83772183.
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http://dx.doi.org/10.1161/JAHA.120.019613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403315PMC
July 2021

Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults.

J Am Coll Cardiol 2021 Jun;77(25):3145-3156

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

Background: The neurocognitive effect of statins in older adults remain uncertain.

Objectives: The aim of this study was to investigate the associations of statin use with cognitive decline and incident dementia among older adults.

Methods: This analysis included 18,846 participants ≥65 years of age in a randomized trial of aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially and were followed for 4.7 years. Outcome measures included incident dementia and its subclassifications (probable Alzheimer's disease, mixed presentations); mild cognitive impairment (MCI) and its subclassifications (MCI consistent with Alzheimer's disease, other MCI); and changes in domain-specific cognition, including global cognition, memory, language and executive function, psychomotor speed, and the composite of these domains. Associations of baseline statin use versus nonuse with dementia and MCI outcomes were examined using Cox proportional hazards models and with cognitive change using linear mixed-effects models, adjusting for potential confounders. The impact of statin lipophilicity on these associations was further examined, and effect modifiers were identified.

Results: Statin use versus nonuse was not associated with dementia, MCI, or their subclassifications or with changes in cognitive function scores over time (p > 0.05 for all). No differences were found in any outcomes between hydrophilic and lipophilic statin users. Baseline neurocognitive ability was an effect modifier for the associations of statins with dementia (p for interaction < 0.001) and memory change (p for interaction = 0.02).

Conclusions: In adults ≥65 years of age, statin therapy was not associated with incident dementia, MCI, or declines in individual cognition domains. These findings await confirmation from ongoing randomized trials.
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http://dx.doi.org/10.1016/j.jacc.2021.04.075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091356PMC
June 2021

A Prospective Study of Diurnal Cortisol and Incident Dementia in Community-Dwelling Older Adults.

J Alzheimers Dis 2021 ;82(3):899-904

Biological Neuropsychiatry Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Diurnal salivary cortisol was measured in 334 older adults without dementia, at four times on two separate days, under quiet and stressful conditions. In multivariate Cox proportional hazard models, higher global diurnal cortisol secretion was associated with incident dementia (HR = 1.09 [1.02-1.15] per one-unit increase in cortisol measure, p = 0.007) and Alzheimer's disease (HR = 1.12 [1.04-1.21], p = 0.003) over a mean (SD) of 8.1 (4.0) years, independent of potential confounders and stressful conditions. Individuals with incident dementia had a slower rate of cortisol elimination under non-stressful conditions, reflected by higher cortisol levels in the evening, and an abnormal response to stress (blunted evening stress response).
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http://dx.doi.org/10.3233/JAD-210389DOI Listing
September 2021

Effect of APOE and a polygenic risk score on incident dementia and cognitive decline in a healthy older population.

Aging Cell 2021 06 26;20(6):e13384. Epub 2021 May 26.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia.

Few studies have measured the effect of genetic factors on dementia and cognitive decline in healthy older individuals followed prospectively. We studied cumulative incidence of dementia and cognitive decline, stratified by APOE genotypes and polygenic risk score (PRS) tertiles, in 12,978 participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial. At enrolment, participants had no history of diagnosed dementia, cardiovascular disease, physical disability or cognitive impairment. Dementia (adjudicated trial endpoint) and cognitive decline, defined as a >1.5 standard deviation decline in test score for either global cognition, episodic memory, language/executive function or psychomotor speed, versus baseline scores. Cumulative incidence for all-cause dementia and cognitive decline was calculated with mortality as a competing event, stratified by APOE genotypes and tertiles of a PRS based on 23 common non-APOE variants. During a median 4.5 years of follow-up, 324 participants developed dementia, 503 died. Cumulative incidence of dementia to age 85 years was 7.4% in all participants, 12.6% in APOE ε3/ε4 and 26.6% in ε4/ε4. APOE ε4 heterozygosity/homozygosity was associated with a 2.5/6.3-fold increased dementia risk and 1.4/1.8-fold cognitive decline risk, versus ε3/ε3 (p < 0.001 for both). High PRS tertile was associated with a 1.4-fold dementia risk versus low (CI 1.04-1.76, p = 0.02), but was not associated with cognitive decline (CI 0.96-1.22, p = 0.18). Incidence of dementia among healthy older individuals is low across all genotypes; however, APOE ε4 and high PRS increase relative risk. APOE ε4 is associated with cognitive decline, but PRS is not.
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http://dx.doi.org/10.1111/acel.13384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208779PMC
June 2021

Steroid 21-hydroxylase gene variants and late-life depression.

BMC Res Notes 2021 May 25;14(1):203. Epub 2021 May 25.

Biological Neuropsychiatry and Dementia Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Objectives: A feature of late-life depression is alterations of the stress hormone system. The CYP21A2 gene encodes for the steroid 21-hydroxylase enzyme which is required for the biosynthesis of mineralocorticoids and glucocorticoids, two main components of the stress response in humans. Variants in the CYP21A2 gene could influence risk of late-life depression, but this has not been examined. This study investigated possible associations between five variants in the CYP21A2 gene and late-life depression in 1007 older community-dwelling men and women.

Results: In multivariate logistic regression model, significant associations were found between three single-nucleotide polymorphisms (rs389883, rs437179, and rs630379) and depression in women specifically (OR ranging from 1.51 to 1.68, p-values 0.025 to 0.0045), and the two latter remained significant after correction for multiple testing. Variants of the CYP21A2 gene appear as susceptibility factors for late-life depression in a sex-specific manner, independently of somatic and neuropsychiatric comorbidity.
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http://dx.doi.org/10.1186/s13104-021-05616-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147346PMC
May 2021

Structural brain alterations in older adults exposed to early-life adversity.

Psychoneuroendocrinology 2021 07 15;129:105272. Epub 2021 May 15.

INM, Univ Montpellier, INSERM, Montpellier, France.

Background: Adverse childhood events may have differential effects on the brain that persist into adulthood. Findings on structural brain alterations in older adults exposed to early-life adversity are inconsistent notably due to heterogeneity in imaging studies, population, psychiatric comorbidities, nature of adverse events, and genetic vulnerability. This study examines whether exposure related to physical or sexual maltreatment, emotional maltreatment, and global adverse environment during childhood are associated with specific alterations in grey matter volumes and if this varies according to sex and serotonin transporter-linked promoter region (5-HTTLPR) genotype.

Method: Structural MRI was used to acquire anatomical scans from 398 community-dwelling older adults. Quantitative regional estimates of 23 subregional volumes were derived using FreeSurfer software. Retrospective reporting of childhood adversity was collected using structured self-reported questionnaire. Analyses adjusted for age, sex, brain volume, head injury, lifetime depression and anxiety disorder, psychiatric medication, and cardiovascular ischemic pathologies.

Results: Exposure to adverse family environment was associated with smaller volumes of several frontal, cingulate, and parietal subregions and larger amygdala in the 5-HTTLPR SS genotype participants specifically but larger volumes of caudate, putamen, pallidum, and nucleus accumbens in the SL genotype participants. Highly significant differences were found with excessive sharing of parent problems with children, associated with larger grey-matter volumes in the thalamus and several frontal and parietal regions in 5-HTTLPR SL male participants specifically.

Conclusions: Early-life adversity is associated with grey-matter volume alterations in older adults and this varies according to the type of adversity experienced, sex, and serotonergic genetic vulnerability; 5-HTTLPR SS participants appearing most vulnerable and SL individuals most resilient.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105272DOI Listing
July 2021

Intergenerational effects of maternal post-traumatic stress disorder on offspring epigenetic patterns and cortisol levels.

Epigenomics 2021 Jun 17;13(12):967-980. Epub 2021 May 17.

Biological Neuropsychiatry Unit, School of Public Health & Preventive Medicine, Monash University, Melbourne 3004, Australia.

To investigate the association between maternal post-traumatic stress disorder (PTSD) during pregnancy and offspring DNA methylation and cortisol levels. Blood genome-wide DNA methylation and cortisol was measured in the youngest child of 117 women who experienced sexual violence/torture during the Kosovo war. Seventy-two percent of women had PTSD symptoms during pregnancy. Their children had higher cortisol levels and differential methylation at candidate genes (, and ) No methylation differences reached epigenome-wide corrected significance levels. Identifying the biological processes whereby the negative effects of trauma are passed across generations and defining groups at high risk is a key step to breaking the intergenerational transmission of the effects of mental disorders.
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http://dx.doi.org/10.2217/epi-2021-0015DOI Listing
June 2021

Trajectories of cognitive function in community-dwelling older adults: A longitudinal study of population heterogeneity.

Alzheimers Dement (Amst) 2021 2;13(1):e12180. Epub 2021 May 2.

School of Public Health and Preventive Medicine Monash University Melbourne Australia.

Introduction: This study aimed to investigate cognitive aging trajectories, the associated sociodemographic characteristics, and the association of these trajectories with dementia.

Methods: Generally healthy older adults (n = 19,114) were followed for up to 7 years, with regular cognitive assessments. Group-based trajectory modeling identified distinct cognitive trajectories.

Results: Four to seven trajectories were identified per cognitive domain. Stable trajectories were observed across domains. Improvement in verbal fluency and minor psychomotor slowing were common. Substantial decline in global cognition and episodic memory were observed in a small proportion of individuals. Older, less educated participants and men were more common in lower-functioning trajectories ( < .001). The highest proportions of dementia cases were in trajectories with major decline in global cognition (56.9%) and memory (33.2%).

Discussion: Inter-individual variability in cognitive trajectories was observed across all domains. Some individuals appear resilient to cognitive decline even with advancing age. Further research into factors promoting cognitive resilience is needed.
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http://dx.doi.org/10.1002/dad2.12180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088593PMC
May 2021

A Cohort Study of Anticholinergic Medication Burden and Incident Dementia and Stroke in Older Adults.

J Gen Intern Med 2021 06 22;36(6):1629-1637. Epub 2021 Mar 22.

Department of Pharmacy Practice and Science, College of Pharmacy and Department of Family Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.

Background: Anticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking.

Objective: Compare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people.

Design: Prospective cohort study.

Setting: Primary care (Australia and USA).

Participants: 19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100.

Measurements: Baseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition.

Results: At baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1-2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications.

Limitations: Residual confounding and reverse causality are possible. Assessment of dose or duration was not possible.

Conclusions: High anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people.
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http://dx.doi.org/10.1007/s11606-020-06550-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175463PMC
June 2021

The Utility of Assessing Health-Related Quality of Life to Predict Cognitive Decline and Dementia.

J Alzheimers Dis 2021 ;80(2):895-904

School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Background: Health-related quality of life (HRQoL) has been shown to predict adverse health outcome in the general population.

Objective: We examined the cross-sectional association between HRQoL and cognitive performance at baseline. Next, we explored whether baseline HRQoL predicted 5-year incident cognitive decline and dementia and whether there were gender differences.

Methods: 19,106 community-dwelling participants from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, aged 65-98 years, free of major cognitive impairments, and completed the HRQoL 12-item short-form (SF-12) at baseline (2010-2014), were followed until June 2017. The physical (PCS) and mental component scores (MCS) of SF-12 were calculated. The cognitive tests were assessed at baseline, year 1, 3, 5, and 7 or close-out visit. Cognitive decline was defined as > 1.5 SD drop from baseline on any of the cognitive tests. Dementia was adjudicated according to DSM-IV criteria. Linear and Cox proportional-hazards regressions were used to examine the cross-sectional and longitudinal associations respectively.

Results: At baseline, higher PCS and MCS were associated with better cognition. Over a median 4.7-year follow-up, higher MCS was associated with a reduced risk of cognitive decline and dementia (12% and 15% respectively, per 10-unit increase) and a 10-unit higher PCS was associated with a 6% decreased risk of cognitive decline. PCS did not predict dementia incidence. Findings were not different by gender.

Conclusion: Our study found that higher HRQoL, in particular MCS, predicted a reduced risk of cognitive decline and dementia over time in community-dwelling older people.
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http://dx.doi.org/10.3233/JAD-201349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093030PMC
September 2021

Optimizing Palbociclib Therapy Across the Age Spectrum: Hypothetical, Illustrative Case Scenarios in HR+, HER2-Metastatic Breast Cancer.

J Adv Pract Oncol 2020 Sep-Oct;11(7):700-719. Epub 2020 Sep 1.

Community Physicians Network, Indianapolis, Indiana.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in combination with endocrine therapy are a preferred treatment option for premenopausal and postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Palbociclib is a potent, first-in-class oral inhibitor of CDK4/6. To provide optimal care to patients with HR+/HER2- mBC receiving palbociclib, advanced practitioners require a thorough understanding of the efficacy and adverse event (AE) profile of palbociclib as well as the diverse characteristics and support needs of patients eligible for palbociclib treatment. This Grand Rounds uses two hypothetical patient scenarios to illustrate core issues in the management of premenopausal and postmenopausal patients receiving palbociclib-based therapy for mBC. In addition to providing an overview of key efficacy and safety data, each case offers practical guidance on providing individualized, patient-centered care, the identification and management of treatment-related AEs, management of concomitant medications, and best practices to promote adherence to therapy.
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http://dx.doi.org/10.6004/jadpro.2020.11.7.5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646629PMC
September 2020

Health-related quality of life and all-cause mortality among older healthy individuals in Australia and the United States: a prospective cohort study.

Qual Life Res 2021 Apr 3;30(4):1037-1048. Epub 2021 Jan 3.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road, Melbourne, VIC, 3004, Australia.

Purpose: Previous research has demonstrated that lower health-related quality of life (HRQoL) is associated with higher morbidity and mortality, especially in-patient groups. The association of HRQoL with all-cause mortality in community samples requires further investigation. This study aimed to examine whether HRQoL predicts all-cause mortality in older healthy community-dwelling people from Australia and the United States (U.S.) enrolled in the Aspirin in Reducing Events in the Elderly (ASPREE) trial. We also explored whether this association varies by gender or country.

Method: A prospective cohort of 19,106 individuals aged 65-98 years, who were without a dementia diagnosis or a known major life-limiting disease, and completed the 12-item short-form-HRQoL at recruitment (2010-2014). They were followed until June 2017. Cox proportional-hazard models were used to determine the association between the physical (PCS) and mental component scores (MCS) of HRQoL and all-cause mortality, adjusting for sociodemographic factors, health-related behaviours and clinical measures. Hazards ratios were estimated for every 10-unit increase in PCS or MCS.

Results: There were 1052 deaths over a median 4.7-years (interquartile range 3.6-5.7) of follow-up, with 11.9 events per 1000 person-years. Higher PCS was associated with lower all-cause mortality (HR 0.83, 95% CI 0.77, 0.89) in the entire sample, while higher MCS was associated with lower mortality among U.S. participants only (HR 0.78, 95% CI 0.63, 0.95). Gender differences in the association of either PCS or MCS with mortality were not observed.

Conclusion: Our large study provides evidence that HRQoL is inversely associated with all-cause mortality among initially healthy older people.
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http://dx.doi.org/10.1007/s11136-020-02723-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005489PMC
April 2021

Effect of Aspirin on Activities of Daily Living Disability in Community-Dwelling Older Adults.

J Gerontol A Biol Sci Med Sci 2021 Oct;76(11):2007-2014

Center for Aging and Population Health, University of Pittsburgh, Pennsylvania, USA.

Background: Cerebrovascular events, dementia, and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin's effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults.

Methods: The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100 mg aspirin versus placebo recruited 19 114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the United States. Six basic ADLs were assessed every 6 months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after 6 months. Proportional hazards modeling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk.

Results: Over a median of 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing, and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 vs 5.3 events/1000 py; hazard ratio [HR] = 0.81, 95% confidence interval [CI]: 0.66-1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability, there were more deaths in the aspirin group (24 vs 12).

Discussion: Low-dose aspirin in initially healthy older people did not reduce the risk of incident ADL disability, although there was evidence of reduced persistent ADL disability.
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http://dx.doi.org/10.1093/gerona/glaa316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514067PMC
October 2021

DNA methylation analysis of candidate genes associated with dementia in peripheral blood.

Epigenomics 2020 12 10;12(23):2109-2123. Epub 2020 Dec 10.

School of Public Health & Preventive Medicine, Monash University, Melbourne, 3004 Victoria, Australia.

To investigate whether genes implicated in dementia pathogenesis are differently methylated in peripheral blood. Participants included 160 cognitively healthy individuals aged 70+ years: 73 who were subsequently diagnosed with dementia and 87 controls matched on age, gender, education, smoking and baseline cognition. A total of 49 participants also provided blood samples at diagnosis. Blood DNA methylation of and was examined. A total of 56 of 299 probes were differentially methylated in dementia compared with controls and 39 probes prior to diagnosis. The greatest effect size was in (cg19423170, Δ-8.32%, adjusted p = 0.009 at diagnosis; cg19933173, Δ-4.18%, adjusted p < 0.0001 prediagnosis). Genes implicated in dementia pathogenesis show differential blood methylation in dementia, even prior to diagnosis.
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http://dx.doi.org/10.2217/epi-2020-0236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008206PMC
December 2020

Distinct Cognitive Trajectories in Late Life and Associated Predictors and Outcomes: A Systematic Review.

J Alzheimers Dis Rep 2020 Oct 24;4(1):459-478. Epub 2020 Oct 24.

School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Background: Cognitive aging is a dynamic process in late life with significant heterogeneity across individuals.

Objective: To review the evidence for latent classes of cognitive trajectories and to identify the associated predictors and outcomes.

Methods: A systematic search was performed in MEDLINE and EMBASE for articles that identified two or more cognitive trajectories in adults. The study was conducted following the PRISMA statement.

Results: Thirty-seven studies were included, ranging from 219 to 9,704 participants, with a mean age of 60 to 93.4 years. Most studies ( = 30) identified distinct cognitive trajectories using latent class growth analysis. The trajectory profile commonly consisted of three to four classes with progressively decreasing baseline and increasing rate of decline-a 'stable-high' class characterized as maintenance of cognitive function at high level, a 'minor-decline' class or 'stable-medium' class that declines gradually over time, and a 'rapid-decline' class with the steepest downward slope. Generally, membership of better classes was predicted by younger age, being female, more years of education, better health, healthier lifestyle, higher social engagement and lack of genetic risk variants. Some factors (e.g., education) were found to be associated with cognitive function over time only within individual classes.

Conclusion: Cognitive aging in late life is a dynamic process with significant inter-individual variability. However, it remains unclear whether similar patterns of cognitive aging are observed across all cognitive domains. Further research into unique factors which promote the maintenance of high-cognitive function is needed to help inform public policy.
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http://dx.doi.org/10.3233/ADR-200232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683100PMC
October 2020

11β-Hydroxylase (CYP11B1) gene variants and new-onset depression in later life.

J Psychiatry Neurosci 2021 01 4;46(1):E147-E153. Epub 2021 Jan 4.

From Inserm, Université Montpellier, Neuropsychiatry: Epidemiological and Clinical Research, Montpellier, France (Ancelin, Norton, Ritchie, Chaudieu, Ryan); the Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (Ritchie); and the Biological Neuropsychiatry and Dementia Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (Ryan).

Background: Cumulative exposure to high glucocorticoid levels is detrimental for the brain and may have particular implications in later life. A feature of late-life depression is increased cortisol secretion. Variants in the CYP11B1 gene, which codes for the enzyme responsible for cortisol synthesis, could influence risk of late-life depression, but this hypothesis has not been examined. We investigated the associations between variants in the CYP11B1 gene and late-life depression, taking into account history of depression and potential sex-specific effects.

Methods: We assessed depression in 1007 community-dwellers aged 65 years or older (60% women) at baseline and over a 14-year follow-up. A clinical level of depression was defined as a score of ≥ 16 on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). We examined incident and recurrent depression in participants without or with a history of major depression, respectively. We genotyped 5 single-nucleotide polymorphisms (SNPs) spanning CYP11B1. We used multivariable analyses to adjust for age, body mass index, cardiovascular ischemic pathologies, hypertension, cognitive impairment and anxiety.

Results: In women, rs6471580 and rs7016924 were associated with a 50% lower rate of incident (new-onset) late-life depression, and rs11783855 was associated with a 2.4-fold higher rate of late-life depression. These associations remained after correction for multiple testing, but we found no associations for recurrent depression in women or men.

Limitations: This study focused on the major gene involved in corticosteroid biosynthesis, but other genes may also be implicated in this pathway.

Conclusion: Variants of the CYP11B1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner.
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http://dx.doi.org/10.1503/jpn.190177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955840PMC
January 2021

Glasdegib plus low-dose cytarabine for acute myeloid leukemia: Practical considerations from advanced practitioners and pharmacists.

J Oncol Pharm Pract 2021 Apr 20;27(3):658-672. Epub 2020 Nov 20.

Department of Leukemia, Dana-Farber Cancer Institute, Boston, MA, USA.

Objective: Acute myeloid leukemia (AML) is primarily a disease of older adults. These patients may not be candidates for intensive treatment, and there has been an ongoing need for treatment options for this group. We review the use of glasdegib, a hedgehog-pathway inhibitor available for use in combination with low-dose cytarabine (LDAC). PubMed and relevant congress abstracts were searched using the term "glasdegib". In addition, based on our experience with glasdegib, we considered treatment aspects of particular relevance to pharmacists and advanced practitioners. In a randomized phase II study, the combination of glasdegib plus LDAC demonstrated superior overall survival versus LDAC alone (hazard ratio 0.51, 80% confidence interval 0.39-0.67,  = 0.0004). The trial reported adverse events (AEs) of special relevance for older patients, such as hematologic events, gastrointestinal toxicity, and fatigue, as well as AEs associated with Hh-pathway inhibitors (alopecia, muscle spasms, dysgeusia). Educating patients about typical AEs can facilitate adherence as well as early AE identification and proactive management. For LDAC, which is a long-established therapy in AML, various stages of delivery need consideration, with attention to individual circumstances. Practical measures such as dispensing a longer supply can reduce the number of return clinic visits, providing a meaningful difference for many patients.

Conclusions: Pharmacists and advanced practitioners play important roles in treatment with glasdegib plus LDAC. Ultimately, framing plans for treatment delivery within the individual circumstances of each patient may enable them to stay on therapy longer, giving them the greatest potential to achieve benefit.
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http://dx.doi.org/10.1177/1078155220973737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008421PMC
April 2021

The association of weight change and all-cause mortality in older adults: a systematic review and meta-analysis.

Age Ageing 2021 05;50(3):697-704

School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Objective: there may be age-related differences in the impact of weight change on health. This study systematically reviewed the evidence on the relationship between weight change and all-cause mortality in adults aged 65 years and older.

Methods: MEDLINE, EMBASE and CINAHL were searched from inception to 11 June 2020, PROSPERO CRD 42019142268. We included observational studies reporting on the association between weight change and all-cause mortality in older community-dwelling adults. A random-effects meta-analysis was performed to calculate pooled hazard ratios and scored based on the Agency for Healthcare Research and Quality guidelines.

Results: a total of 30 studies, including 1,219,279 participants with 69,255 deaths, demonstrated that weight loss was associated with a 59% increase in mortality risk (hazard ratio (HR): 1.59; 95% confidence interval (CI): 1.45-1.74; P < 0.001). Twenty-seven studies that reported outcomes for weight gain (1,210,116 participants with 65,481 deaths) indicated that weight gain was associated with a 10% increase in all-cause mortality (HR: 1.10; 95%CI: 1.02, 1.17; P = 0.01). Four studies investigated weight fluctuation (2,283 events among 6,901 participants), which was associated with a 63% increased mortality risk (HR: 1.66; 95%CI: 1.28, 2.15). No evidence of publication bias was observed (all P > 0.05).

Conclusion: for community-dwelling older adults, weight changes (weight loss, gain or weight fluctuation) are associated with an increased risk of all-cause mortality risk relative to stable weight. Further research is needed to determine whether these associations vary depending upon initial weight, and whether or not the weight loss/gain was intentional.
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http://dx.doi.org/10.1093/ageing/afaa231DOI Listing
May 2021

Quality of life and mortality in the general population: a systematic review and meta-analysis.

BMC Public Health 2020 Nov 6;20(1):1596. Epub 2020 Nov 6.

School of Public Health and Preventive Medicine, Monash University, 99 Commercial Road, Melbourne, VIC, 3004, Australia.

Background: Quality of life (QoL) is multi-dimensional concept of an individual' general well-being status in relation to their value, environment, cultural and social context in which they live. This study aimed to quantitatively synthesise available evidence on the association between QoL and mortality in the general population.

Methods: An electronic search was conducted using three bibliographic databases, MEDLINE, EMBASE and PsycINFO. Inclusion criteria were studies that assessed QoL using standardized tools and examined mortality risk in a non-patient population. Qualitative data synthesis and meta-analyses using a random-effects model were performed.

Results: Of 4184 articles identified, 47 were eligible for inclusion, involving approximately 1,200,000 participants. Studies were highly heterogeneous in terms of QoL measures, population characteristics and data analysis. In total, 43 studies (91.5%) reported that better QoL was associated with lower mortality risk. The results of four meta-analyses indicated that higher health-related QoL (HRQoL) is associated with lower mortality risk, which was consistent for overall HRQoL (HR 0.633, 95% CI: 0.514 to 0.780), physical function (HR 0.987, 95% CI: 0.982 to 0.992), physical component score (OR 0.950, 95% CI: 0.935 to 0.965), and mental component score (OR 0.980, 95% CI: 0.969 to 0.992).

Conclusion: These findings provide evidence that better QoL/HRQoL was associated with lower mortality risk. The utility of these measures in predicting mortality risk indicates that they should be considered further as potential screening tools in general clinical practice, beyond the traditional objective measures such as body mass index and the results of laboratory tests.
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http://dx.doi.org/10.1186/s12889-020-09639-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646076PMC
November 2020

Long-Term Blood Pressure Variability and Risk of Cardiovascular Disease Events Among Community-Dwelling Elderly.

Hypertension 2020 12 2;76(6):1945-1952. Epub 2020 Nov 2.

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia (E.K.C., R.W., A.M.T., J.R., R.L.W., J.J.M., C.M.R.).

High office blood pressure variability (OBPV) in midlife increases the risk of cardiovascular disease (CVD), but the impact of OBPV in older adults without previous CVD is unknown. We conducted a post hoc analysis of ASPREE trial (Aspirin in Reducing Events in the Elderly) participants aged 70-years and older (65 for US minorities) without history of CVD events at baseline, to examine risk of incident CVD associated with long-term, visit-to-visit OBPV. CVD was a prespecified, adjudicated secondary end point in ASPREE. We estimated OBPV using within-individual SD of mean systolic BP from baseline and first 2 annual visits. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% CI for associations with CVD events. In 16 475 participants who survived to year 2 without events, those in the highest tertile of OBPV had increased risk of CVD events after adjustment for multiple covariates, when compared with participants in the lowest tertile (HR, 1.36 [95% CI, 1.08-1.70]; =0.01). Similar increased risk was observed for ischemic stroke (HR, 1.56 [95% CI, 1.04-2.33]; =0.03), heart failure hospitalization, or death (HR, 1.73 [95% CI, 1.07-2.79]; =0.02), and all-cause mortality (HR, 1.27 [95% CI, 1.04-1.54]; =0.02). Findings were consistent when stratifying participants by use of antihypertensive drugs, while sensitivity analyses suggested the increased risk was especially for individuals whose BP was uncontrolled during the OBPV estimation period. Our findings support increased OBPV as a risk factor for CVD events in healthy older adults with, or without hypertension, who have not had such events previously. Registration- URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01038583; URL: https://www.isrctn.com; Unique identifiers: ISRCTN83772183.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666049PMC
December 2020
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