The relationship between alcohol use and dementia: A combined analysis of prospective, individual-participant data from 15 international studies

Objective: To synthesise international findings on the alcohol-dementia relationship and provide a cross-national comparison of the alcohol-dementia relationship with critical evidence for the relationship between alcohol use and dementia in under-studied populations. Design and setting: Individual participant data meta-analysis of 15 prospective epidemiological cohort studies from countries situated in five continents. Cox regression investigated the dementia risk associated with alcohol use. Sensitivity analyses compared lifetime abstainers with former drinkers, adjusted extensively for demographic and clinical characteristics, and assessed the competing risk of death. Participants: 24,472 community-dwelling individuals without a history of dementia at baseline and at least one follow-up dementia assessment. Main outcome measure: All-cause dementia as determined by clinical interview. Results: During 151,574 person-years of follow-up, there were 2,137 incident cases of dementia (14.1 per 1,000 person-years). In the combined sample, when compared with occasional drinkers (<1.3g/day), the risk for dementia was higher for current abstainers (HR: 1.29; 95% CI: 1.13, 1.48) and lower for moderate drinkers (25g/day-44.9g/day; HR: 0.79; 95% CI: 0.64, 0.98). When the combined sample was stratified by sex and gross domestic product, current abstainers had a greater risk of incident dementia when compared with light-to-moderate drinkers in both sexes and in the higher income countries. When comparing lifetime abstainers and former drinkers there were no consistent differences in dementia risk. Among current drinkers, there was no consistent evidence to suggest that the amount of alcohol consumed in later life was significantly associated with dementia risk. Adjusting for additional demographic and clinical covariates, and accounting for competing risk of death, did not substantially affect results. When analysed at the cohort level, there was considerable heterogeneity in the alcohol-dementia relationship. Conclusions: In a large and diverse international sample of older adults, the current study found that abstinence from alcohol is associated with an increased risk for all-cause dementia. Among current drinkers, there was no consistent evidence to suggest that the amount of alcohol consumed in later life was significantly associated with dementia risk.

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The Association of Atrial Fibrillation and Ischemic Stroke in Patients on Hemodialysis: A Competing Risk Analysis

Canadian Journal of Kidney Health and Disease ◽

10.1177/2054358119878719 ◽

2019 ◽

Vol 6 ◽

pp. 205435811987871 ◽

Cited By ~ 4

Author(s):

Mark Findlay ◽

Rachael MacIsaac ◽

Mary Joan MacLeod ◽

Wendy Metcalfe ◽

Manish M. Sood ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Stroke Risk ◽

Competing Risk ◽

Discharge Data ◽

Stroke Incidence ◽

Risk Of Death ◽

Hazards Model ◽

The Relationship

Background: Stroke is common in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) and associated with high mortality rate. In the general population, atrial fibrillation (AF) is a major risk factor for stroke and therapeutic anticoagulation is associated with risk reduction, whereas in ESRD the relationship is less clear. Objective: The purpose of this study is to demonstrate the influence of AF on stroke rates and probability in those on HD following competing risk analyses. Design: A national record linkage cohort study. Setting: All renal and stroke units in Scotland, UK. Patients: All patients with ESRD receiving HD within Scotland from 2005 to 2013 (follow-up to 2015). Measurements: Demographic, clinical, and laboratory data were linked between the Scottish Renal Registry, Scottish Stroke Care Audit, and hospital discharge data. Stroke was defined as a fatal or nonfatal event and mortality derived from national records. Methods: Associations for stroke were determined using competing risk models: the cause-specific hazards model and the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of all stroke, ischemic stroke, and first-ever stroke. Results: Of 5502 patients treated with HD with 12 348.6-year follow-up, 363 (6.6%) experienced stroke. The stroke incidence rate was 26.7 per 1000 patient-years. Multivariable regression on the cause-specific hazard for stroke demonstrated age, hazard ratio (HR) (95% confidence interval [CI]) = 1.04 (1.03-1.05); AF, HR (95% CI) = 1.88 (1.25-2.83); prior stroke, HR (95% CI) = 2.29 (1.48-3.54), and diabetes, HR (95% CI) = 1.92 (1.45-2.53); serum phosphate, HR (95% CI) = 2.15 (1.56-2.99); lower body weight, HR (95% CI) = 0.99 (0.98-1.00); lower hemoglobin, HR (95% CI) = 0.88 (0.77-0.99); and systolic blood pressure (BP), HR (95% CI) = 1.01 (1.00-1.02), to be associated with an increased stroke rate. In contrast, the subdistribution HRs obtained following Fine and Gray regression demonstrated that AF, weight, and hemoglobin were not associated with stroke risk. In both models, AF was significantly associated with nonstroke death. Limitations: Our analyses derive from retrospective data sets and thus can only describe association not causation. Data on anticoagulant use are not available. Conclusions: The incidence of stroke in HD patients is high. The competing risk of “prestroke” mortality affects the relationship between AF and risk of future stroke. Trial designs for interventions to reduce stroke risk in HD patients, such as anticoagulation for AF, should take account of competing risks affecting associations between risk factors and outcomes.

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Long working hours and alcohol use: systematic review and meta-analysis of published studies and unpublished individual participant data

BMJ ◽

10.1136/bmj.g7772 ◽

2015 ◽

Vol 350 (jan12 13) ◽

pp. g7772-g7772 ◽

Cited By ~ 77

Author(s):

M. Virtanen ◽

M. Jokela ◽

S. T. Nyberg ◽

I. E. H. Madsen ◽

T. Lallukka ◽

...

Keyword(s):

Systematic Review ◽

Alcohol Use ◽

Meta Analysis ◽

Working Hours ◽

Individual Participant Data ◽

Long Working Hours ◽

Individual Participant

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Prospective Associations of Physical Frailty With Future Falls and Fear of Falling: A 48-Month Cohort Study

Physical Therapy ◽

10.1093/ptj/pzab059 ◽

2021 ◽

Author(s):

K Makino ◽

S Lee ◽

S Bae ◽

I Chiba ◽

K Harada ◽

...

Keyword(s):

Older Adults ◽

Cohort Study ◽

Fear Of Falling ◽

Community Dwelling ◽

Cardiovascular Health Study ◽

Physical Frailty ◽

Frailty Status ◽

Community Dwelling Older Adults ◽

The Relationship

Abstract Objective The present study aimed to examine the prospective associations of physical frailty with future falls and fear of falling (FOF) among community-dwelling older adults. Methods A prospective cohort study with a 48-month follow-up was conducted in a Japanese community. Participants were 2469 community-dwelling older adults aged 65 years or older who completed baseline and follow-up assessments at intervals of 48±2 months. Primary outcomes were recent falls (defined as at least one fall within the past year) and FOF (determined by response to “Are you afraid of falling?”) at follow-up survey. Physical frailty, operationalized by the frailty phenotype (slowness, weakness, exhaustion, weight loss, and low activity) based on the criteria of the Japanese version of the Cardiovascular Health Study (J-CHS), was also assessed as a predictor of future falls and FOF. Results Multivariate logistic regression showed that pre-frailty or frailty increase the risk of not only future falls (OR: 1.57; 95%CI = 1.20-2.05) but also FOF (OR: 1.33; 95%CI = 1.05-1.69). In addition, the relationship between baseline frailty status and future falls remained significant after adjusting for baseline FOF (OR: 1.55; 95%CI = 1.19-2.02), and the relationship between baseline frailty status and future FOF also remained significant after adjusting for baseline falls (OR: 1.32; 95%CI = 1.04-1.68). Conclusions Frailty status may predict future falls and FOF among community-dwelling older adults. Strategies to prevent frailty may be beneficial to prevent not only future falls but also future FOF in a community setting. Impact Falls and FOF have a close relationship but a different clinical meaning. Older adults with physical frailty may require monitoring as high-risk not only for falls but also for FOF.

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The relationship between muscle quality and incidence of falls in older community-dwelling women: An 18-month follow-up study

Experimental Gerontology ◽

10.1016/j.exger.2018.06.018 ◽

2018 ◽

Vol 110 ◽

pp. 241-246 ◽

Cited By ~ 7

Author(s):

André Bonadias Gadelha ◽

Silvia Gonçalves Ricci Neri ◽

Martim Bottaro ◽

Ricardo M. Lima

Keyword(s):

Community Dwelling ◽

Muscle Quality ◽

Follow Up Study ◽

The Relationship

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Abstract P014: Lower eGFR and Proteinuria Were Independently Associated With Lower Cognitive Abilities in Community-dwelling Men in Japan: SESSA study

Circulation ◽

10.1161/circ.135.suppl_1.p014 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Akira Fujiyoshi ◽

Takayoshi Ohkubo ◽

Katsuyuki Miura ◽

Akihiko Shiino ◽

Naoko Miyagawa ◽

...

Keyword(s):

Cognitive Function ◽

Cognitive Abilities ◽

Estimated Glomerular Filtration Rate ◽

Subclinical Atherosclerosis ◽

Community Dwelling ◽

Community Based ◽

Lower Egfr ◽

The Mean ◽

The Relationship

Introduction: The relationship between chronic kidney disease (CKD) and cognitive function remains to be determined. Existing studies focused primarily on estimated glomerular filtration rate (eGFR) but not proteinuria in relation to cognitive function. Hypothesis: In a community-based sample, lower eGFR and presence of proteinuria are cross-sectionally independently associated with lower cognition. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited and examined participants from Shiga, Japan in 2006-08 at baseline. Among 824 male participants in the follow-up exam (2010-12), we restricted our analyses to those who underwent the Cognitive Abilities Screening Instrument (CASI), age ≥65 years-old, free of stroke, with no missing pertinent covariates. We calculated eGFR (creatinine-based) according to the 2012-guideline by the Japanese Society of Nephrology. We then divided the participants into three groups by eGFR of ≥60, 59-40, and <40 (mL/min/1.73m 2 ), and separately divided into three groups according to proteinuria using urine dipstick: (-), (-/+), and ≥(1+). We defined CKD as either eGFR <60 or proteinuria ≥ (-/+). In linear regression with CASI score being a dependent variable, we computed the score adjusted for age, highest education attained, smoking, drinking, body mass index, hypertension, diabetes, and dyslipidemia. Results: We analyzed 541 men. The mean [standard deviation] of age and unadjusted score were 72.6 [4.3] years and 89.7 [6.0]. Prevalence of CKD was 56%. The score was significantly lower in participants with CKD than those without it (P=0.03). eGFR and proteinuria categories were separately and jointly associated with lower CASI score in a graded fashion (Ps for trend <0.05 in all the models tested. Table 1 ). Conclusions: Lower eGFR and higher degree of proteinuria were independently associated with lower cognitive function in the community-based men. CKD even in its early phase may predispose to lower cognitive function.

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Mean nocturnal respiratory rate predicts cardiovascular and all-cause mortality in community-dwelling older men and women

European Respiratory Journal ◽

10.1183/13993003.02175-2018 ◽

2019 ◽

Vol 54 (1) ◽

pp. 1802175 ◽

Cited By ~ 3

Author(s):

Mathias Baumert ◽

Dominik Linz ◽

Katie Stone ◽

R. Doug McEvoy ◽

Steve Cummings ◽

...

Keyword(s):

Osteoporotic Fractures ◽

Older Men ◽

Community Dwelling ◽

Sleep Study ◽

Men And Women ◽

All Cause Mortality ◽

The Relationship ◽

Older Men And Women

Respiratory frequency (fR) predicts in-hospital and short-term mortality in patients with a variety of pathophysiological conditions, but its predictive value for long-term cardiovascular and all-cause mortality in the general population is unknown. Here, we investigated the relationship between mean nocturnal fR and mortality in community-dwelling older men and women.We measured mean nocturnal fR during sleep from overnight polysomnography in 2686 men participating in the Osteoporotic Fractures in Men Study (MrOS) Sleep study and 406 women participating in the Study of Osteoporotic Fractures (SOF) to investigate the relationship between mean nocturnal fR and long-term cardiovascular and all-cause mortality.166 (6.1%) men in the MrOS cohort (8.9±2.6 years’ follow-up) and 46 (11.2%) women in the SOF cohort (6.4±1.6 years’ follow-up) died from cardiovascular disease. All-cause mortality was 51.2% and 26.1% during 13.7±3.7 and 6.4±1.6 years’ follow-up in the MrOS Sleep study and the SOF cohorts, respectively. Multivariable Cox regression analysis adjusted for significant covariates demonstrated that fR dichotomised at 16 breaths·min−1 was independently associated with cardiovascular mortality (MrOS: hazard ratio (HR) 1.57, 95% CI 1.14–2.15; p=0.005; SOF: HR 2.58, 95% CI 1.41–4.76; p=0.002) and all-cause mortality (MrOS: HR 1.18, 95% CI 1.04–1.32; p=0.007; SOF: HR 1.50, 95% CI 1.02–2.20; p=0.04).In community-dwelling older men and women, polysomnography-derived mean nocturnal fR ≥16 breaths·min−1 is an independent predictor of long-term cardiovascular and all-cause mortality. Whether nocturnal mean fR can be used as a risk marker warrants further prospective studies.

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Periodontitis Is Associated with Chronic Obstructive Pulmonary Disease

Journal of Dental Research ◽

10.1177/0022034519833630 ◽

2019 ◽

Vol 98 (5) ◽

pp. 534-540 ◽

Cited By ~ 11

Author(s):

K. Takeuchi ◽

K. Matsumoto ◽

M. Furuta ◽

S. Fukuyama ◽

T. Takeshita ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Population Attributable Fraction ◽

Community Dwelling ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Increased Risk ◽

Severe Periodontitis ◽

The Relationship

Although they are known to share pathophysiological processes, the relationship between periodontitis and chronic obstructive pulmonary disease (COPD) is not fully understood. The aim of the present study was to test the hypothesis that periodontitis is associated with a greater risk of development of COPD, when smoking is taken into account. The analysis in a 5-y follow-up population-based cohort study was based on 900 community-dwelling Japanese adults (age: 68.8 ± 6.3 [mean ± SD], 46.0% male) without COPD aged 60 or older with at least 1 tooth. Participants were classified into 3 categories according to baseline periodontitis severity (no/mild, moderate, and severe). COPD was spirometrically determined by a fixed ratio of <0.7 for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and by FEV1/FVC below the lower limit of normal. Poisson regression was used to calculate the relative risk (RR) of developing COPD according to the severity of periodontitis. The population attributable fraction (PAF) was also calculated. During follow-up, 22 (2.4%) subjects developed COPD. Compared with no/mild periodontitis subjects, a significantly increased risk of COPD occurred among severe periodontitis subjects (RR = 3.55; 95% confidence interval [CI], 1.18 to 10.67), but no significant differences were observed between the no/mild and moderate categories (RR = 1.48; 95% CI, 0.56 to 3.90). After adjustment for potential confounders, including smoking intensity, the relationship between severe periodontitis and risk of COPD remained significant (RR = 3.51; 95% CI, 1.15 to 10.74). Likewise, there was a positive association of periodontitis severity with risk of COPD ( P for trend = 0.043). The PAF for COPD due to periodontitis was 22.6%. These data highlight the potential importance of periodontitis as a risk factor for COPD.

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Subclinical thyroid dysfunction and depressive symptoms: protocol for a systematic review and individual participant data meta-analysis of prospective cohort studies

BMJ Open ◽

10.1136/bmjopen-2019-029716 ◽

2019 ◽

Vol 9 (7) ◽

pp. e029716

Author(s):

Lea Wildisen ◽

Elisavet Moutzouri ◽

Shanthi Beglinger ◽

Lamprini Syrogiannouli ◽

Anne R Cappola ◽

...

Keyword(s):

Systematic Review ◽

Depressive Symptoms ◽

Cohort Studies ◽

Prospective Cohort ◽

Thyroid Dysfunction ◽

Meta Analysis ◽

Individual Participant Data ◽

Prospective Cohort Studies ◽

Individual Participant

IntroductionProspective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association.Methods and analysisWe will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model.Ethics and disseminationFormal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal.PROSPERO registration numberCRD42018091627.

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Traumatic brain injury associated with dementia risk among people with type 1 diabetes

Neurology ◽

10.1212/wnl.0000000000006391 ◽

2018 ◽

Vol 91 (17) ◽

pp. e1611-e1618 ◽

Cited By ~ 3

Author(s):

Paola Gilsanz ◽

Kathleen Albers ◽

Michal Schnaider Beeri ◽

Andrew J. Karter ◽

Charles P. Quesenberry ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Type 1 Diabetes ◽

Brain Injury ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Competing Risk ◽

Middle Aged ◽

Risk Of Death ◽

Dementia Risk

ObjectiveTo examine the association between traumatic brain injury (TBI) and dementia risk among a cohort of middle-aged and elderly individuals with type 1 diabetes (T1D).MethodsWe evaluated 4,049 members of an integrated health care system with T1D ≥50 years old between January 1, 1996, and September 30, 2015. Dementia and TBI diagnoses throughout the study period were abstracted from medical records. Cox proportional hazards models estimated associations between time-dependent TBI and dementia adjusting for demographics, HbA1c, nephropathy, neuropathy, stroke, peripheral artery disease, depression, and dysglycemic events. Fine and Gray regression models evaluated the association between baseline TBI and dementia risk accounting for competing risk of death.ResultsA total of 178 individuals (4.4%) experienced a TBI and 212 (5.2%) developed dementia. In fully adjusted models, TBI was associated with 3.6 times the dementia risk (hazard ratio [HR] 3.64; 95% confidence interval [CI] 2.34, 5.68). When accounting for the competing risk of death, TBI was associated with almost 3 times the risk of dementia (HR 2.91; 95% CI 1.29, 5.68).ConclusionThis study demonstrates a marked increase in risk of dementia associated with TBI among middle-aged and elderly people with T1D. Given the complexity of self-care for individuals with T1D, and the comorbidities that predispose them to trauma and falls, future work is needed on interventions protecting brain health in this vulnerable population, which is now living to old age.

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Association of Angiotensin II–Stimulating Antihypertensive Use and Dementia Risk

Neurology ◽

10.1212/wnl.0000000000010996 ◽

2020 ◽

Vol 96 (1) ◽

pp. e67-e80

Author(s):

Jan Willem van Dalen ◽

Zachary A. Marcum ◽

Shelly L. Gray ◽

Douglas Barthold ◽

Eric P. Moll van Charante ◽

...

Keyword(s):

Angiotensin Ii ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Excess Mortality ◽

Population Sample ◽

Community Dwelling ◽

Channel Blockers ◽

Dementia Risk ◽

Incident Dementia

ObjectiveTo assess whether angiotensin II–stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin I receptor blockers) convey a lower risk of incident dementia compared to angiotensin II–inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, β-blockers, and nondihydropyridine calcium channel blockers), in accordance with the “angiotensin hypothesis.”MethodsWe performed Cox regression analyses of incident dementia (or mortality as competing risk) during 6–8 years of follow-up in a population sample of 1,909 community-dwelling individuals (54% women) without dementia, aged 70–78 (mean 74.5 ± 2.5) years.ResultsAfter a median of 6.7 years of follow-up, dementia status was available for 1,870 (98%) and mortality for 1,904 (>99%) participants. Dementia incidence was 5.6% (27/480) in angiotensin II–stimulating, 8.2% (59/721) in angiotensin II–inhibiting, and 6.9% (46/669) in both antihypertensive type users. Adjusted for dementia risk factors including blood pressure and medical history, angiotensin II–stimulating antihypertensive users had a 45% lower incident dementia rate (hazard ratio [HR], 0.55; 95% CI, 0.34–0.89) without excess mortality (HR, 0.86; 95% CI, 0.64–1.16), and individuals using both types had a nonsignificant 20% lower dementia rate (HR, 0.80; 95% CI,0.53–1.20) without excess mortality (HR, 0.97; 95% CI, 0.76–1.24), compared to angiotensin II–inhibiting antihypertensive users. Results were consistent for subgroups based on diabetes and stroke history, but may be specific for individuals without a history of cardiovascular disease.ConclusionsUsers of angiotensin II–stimulating antihypertensives had lower dementia rates compared to angiotensin II–inhibiting antihypertensive users, supporting the angiotensin hypothesis. Confounding by indication must be examined further, although subanalyses suggest this did not influence results. If replicated, dementia prevention could become a compelling indication for older individuals receiving antihypertensive treatment.

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