Plasma Vitamin B12 Levels, High-Dose Vitamin B12 Treatment, and Risk of Dementia

Background: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia. Objective: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer’s disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes). Methods: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000–2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200–600 pmol/L). We used multivariable Cox regression to compute 0–15-year hazard ratios for dementia. Results: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia. Conclusion: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia.

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Headache as a risk factor for dementia: A prospective population-based study

Cephalalgia ◽

10.1177/0333102413513181 ◽

2013 ◽

Vol 34 (5) ◽

pp. 327-335 ◽

Cited By ~ 22

Author(s):

Knut Hagen ◽

Eystein Stordal ◽

Mattias Linde ◽

Timothy J Steiner ◽

John-Anker Zwart ◽

...

Keyword(s):

Risk Factor ◽

Cohort Study ◽

Cox Regression ◽

Subsequent Development ◽

Population Based ◽

Health Study ◽

Cox Regression Analysis ◽

Hazard Ratios ◽

Increased Risk

Background Headache has not been established as a risk factor for dementia. The aim of this study was to determine whether any headache was associated with subsequent development of vascular dementia (VaD), Alzheimer’s disease (AD) or other types of dementia. Methods This prospective population-based cohort study used baseline data from the Nord-Trøndelag Health Study (HUNT 2) performed during 1995–1997 and, from the same Norwegian county, a register of cases diagnosed with dementia during 1997–2010. Participants aged ≥20 years who responded to headache questions in HUNT 2 were categorized (headache free; with any headache; with migraine; with nonmigrainous headache). Hazard ratios (HRs) for later inclusion in the dementia register were estimated using Cox regression analysis. Results Of 51,383 participants providing headache data in HUNT 2, 378 appeared in the dementia register during the follow-up period. Compared to those who were headache free, participants with any headache had increased risk of VaD ( n = 63) (multivariate-adjusted HR = 2.3, 95% CI 1.4–3.8, p = 0.002) and of mixed dementia (VaD and AD ( n = 52)) (adjusted HR = 2.0, 95% CI 1.1–3.5, p = 0.018). There was no association between any headache and later development of AD ( n = 180). Conclusion In this prospective population-based cohort study, any headache was a risk factor for development of VaD.

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Milk drinking and risk of hip fracture: the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS)

British Journal Of Nutrition ◽

10.1017/s0007114518003823 ◽

2019 ◽

Vol 121 (6) ◽

pp. 709-718 ◽

Cited By ~ 3

Author(s):

Kristin Holvik ◽

Haakon E. Meyer ◽

Ida Laake ◽

Diane Feskanich ◽

Tone K. Omsland ◽

...

Keyword(s):

Hip Fracture ◽

Hip Fractures ◽

Cox Regression ◽

Population Based ◽

Third Wave ◽

Hospital Data ◽

High Fracture ◽

Hazard Ratios ◽

Meta Analyses

AbstractMilk provides energy and nutrients considered protective for bone. Meta-analyses of cohort studies have found no clear association between milk drinking and risk of hip fracture, and results of recent studies are contradictory. We studied the association between milk drinking and hip fracture in Norway, which has a population characterised by high fracture incidence and a high Ca intake. Baseline data from two population-based cohorts were used: the third wave of the Norwegian Counties Study (1985–1988) and the Five Counties Study (2000–2002). Diet and lifestyle variables were self-reported through questionnaires. Height and weight were measured. Hip fractures were identified by linkage to hospital data with follow-up through 2013. Of the 35 114 participants in the Norwegian Counties Study, 1865 suffered a hip fracture during 613 018 person-years of follow-up. In multivariable Cox regression, hazard ratios (HR) per daily glass of milk were 0·97 (95 % CI 0·92, 1·03) in men and 1·02 (95 % CI 0·96, 1·07) in women. Of 23 259 participants in the Five Counties Study, 1466 suffered a hip fracture during 252 996 person-years of follow-up. HR for hip fractures per daily glass of milk in multivariable Cox regression was 0·99 (95 % CI 0·92, 1·07) in men and 1·02 (95 % CI 0·97, 1·08) in women. In conclusion, there was no overall association between milk intake and risk of hip fracture in Norwegian men and women.

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1067Annual changes in job strain and risk of coronary heart disease in Denmark

International Journal of Epidemiology ◽

10.1093/ije/dyab168.574 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Jeppe Karl Sørensen ◽

Elisabeth Framke ◽

Ida E.H. Madsen ◽

Reiner Rugulies

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Cox Regression ◽

Job Strain ◽

Population Based ◽

Job Exposure Matrix ◽

Hazard Ratios ◽

Annual Changes ◽

Mean Time

Abstract Background We examined the association between annual changes in job strain and incident coronary heart disease (CHD) in a population-based cohort study in Denmark. Methods We studied all workers residing in Denmark in 2000, aged 30-59 years with no prevalent CHD (N = 1,660,150). Using a job exposure matrix (JEM) with annual updates, we assessed changes in job strain from 2000-2009. Incident CHD was identified in hospital and death registers from 2001 to 2010. Using Cox regression, we calculated hazard ratios (HR) and 95% confidence intervals (CI) for the association between annual changes in job strain and incident CHD. Results During 16.1 million person-years (mean time of follow-up: 9.7 years), we identified 24,159 CHD cases (15.0 per 10,000 person-years). Compared to persistent no job strain, persistent job strain (HR 1.07, 95% CI 1.03–1.10), onset of job strain (HR 1.20, 95% CI 1.12–1.29) and removal of job strain (HR 1.20, 95% CI 1.12–1.28) were associated with higher CHD incidence. Conclusions Persistent and onset of job strain was associated with a higher risk of CHD. Removal of job strain was also associated with a higher risk, which might be due to health selection. Our results suggest that job strain contributes to risk of CHD in the Danish workforce. Key messages Implementing JEM in a population-based cohort of more than 1.6 million workers enabled us to demonstrate associations between annual changes in job strain and risk of incident CHD.

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A population-based longitudinal study of Clostridium difficile infection-related hospitalization in mid-age and older Australians

Epidemiology and Infection ◽

10.1017/s0950268816002260 ◽

2016 ◽

Vol 145 (3) ◽

pp. 575-582 ◽

Cited By ~ 4

Author(s):

Y. CHEN ◽

K. GLASS ◽

B. LIU ◽

T.V. RILEY ◽

R. KORDA ◽

...

Keyword(s):

Clostridium Difficile ◽

Cox Regression ◽

New South ◽

Population Based ◽

Crude Incidence ◽

Median Hospital Stay ◽

Hospitalization Rates ◽

South Wales ◽

Hazard Ratios

SUMMARYClostridium difficile is the principal cause of infectious diarrhoea in hospitalized patients. We investigated the incidence and risk factors for hospitalization due to C. difficile infection (CDI) in older Australians. We linked data from a population-based prospective cohort study (the 45 and Up Study) of 266 922 adults aged ⩾45 years recruited in New South Wales, Australia to hospitalization and death records for 2006–2012. We estimated the incidence of CDI hospitalization and calculated days in hospital and costs per hospitalization. We also estimated hazard ratios (HR) for CDI hospitalization using Cox regression with age as the underlying time variable. Over a total follow-up of 1 126 708 person-years, 187 adults had an incident CDI hospitalization. The crude incidence of CDI hospitalization was 16·6/100 000 person-years, with a median hospital stay of 6 days, and a median cost of AUD 6102 per admission. Incidence increased with age and year of follow-up, with a threefold increase for 2009–2012. After adjustment, CDI hospitalization rates were significantly lower in males than females (adjusted HR 0·6, 95% confidence interval 0·4–0·7). CDI hospitalization rates increased significantly over 2009–2012. There is a need to better understand the increasing risk of CDI hospitalization in women.

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Multimorbidity, functional limitations, and outcomes: Interactions in a population-based cohort of older adults

Journal of Comorbidity ◽

10.1177/2235042x19873486 ◽

2019 ◽

Vol 9 ◽

pp. 2235042X1987348 ◽

Cited By ~ 2

Author(s):

Alanna M Chamberlain ◽

Lila J Finney Rutten ◽

Debra J Jacobson ◽

Chun Fan ◽

Patrick M Wilson ◽

...

Keyword(s):

Older Adults ◽

Cox Regression ◽

Functional Limitations ◽

Population Based ◽

Care Utilization ◽

Synergistic Interactions ◽

Hazard Ratios ◽

Ed Visits ◽

Additive Scale

Objective: To understand the interaction of multimorbidity and functional limitations in determining health-care utilization and survival in older adults. Methods: Olmsted County, Minnesota, residents aged 60–89 years in 2005 were categorized into four cohorts based on the presence or absence of multimorbidity (≥3 chronic conditions from a list of 18) and functional limitations (≥1 limitation in an activity of daily living from a list of 9), and were followed through December 31, 2016. Andersen–Gill and Cox regression estimated hazard ratios (HRs) for emergency department (ED) visits, hospitalizations, and death using persons with neither multimorbidity nor functional limitations as the reference (interaction analyses). Results: Among 13,145 persons, 34% had neither multimorbidity nor functional limitations, 44% had multimorbidity only, 4% had functional limitations only, and 18% had both. Over a median follow-up of 11 years, 5906 ED visits, 2654 hospitalizations, and 4559 deaths occurred. Synergistic interactions on an additive scale of multimorbidity and functional limitations were observed for all outcomes; however, the magnitude of the interactions decreased with advancing age. The HR (95% confidence interval) for death among persons with both multimorbidity and functional limitations was 5.34 (4.40–6.47) at age 60–69, 4.16 (3.59–4.83) at age 70–79, and 2.86 (2.45–3.35) at age 80–89 years. Conclusion: The risk of ED visits, hospitalizations, and death among persons with both multimorbidity and functional limitations is greater than additive. The magnitude of the interaction was strongest for the youngest age group, highlighting the importance of interventions to prevent and effectively manage multimorbidity and functional limitations early in life.

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Visual impairment increases the risk of dementia, especially in young males in a 12-year longitudinal follow-up study of a national cohort

Scientific Reports ◽

10.1038/s41598-021-91026-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ga-In Lee ◽

Sang Ah Chi ◽

Kyunga Kim ◽

Sang Won Seo ◽

Hee Jin Kim ◽

...

Keyword(s):

Visual Impairment ◽

Household Income ◽

Cox Regression ◽

Population Based ◽

Study Cohort ◽

National Data ◽

Young Males ◽

Hazard Ratios ◽

National Cohort

AbstractWe investigated the effect of visual impairment (VI) on dementia development in a national cohort. In this 12-year nationwide population-based retrospective cohort study, national data were collected from National Health Insurance Cooperation of South Korea from 2002 to 2017, comprising 799,074 subjects selected from the dementia-free cohort representative of the Korean population. Crude hazard ratios (HRs) as well as age- and sex-adjusted HRs and confidence intervals (CIs) for the development of dementia were estimated using multivariable Cox regression models. VI significantly increased the risk of dementia with a HR of 2.726 (95% CI 2.251–3.300, p < 0.0001) after adjusting for age, sex, and interaction between age, sex, and VI. HR of interaction between VI and age for dementia was 0.539 (95% CI 0.436–0.667, p < 0.0001). In the sensitivity analysis after adjustment for age, sex, household income level, BMI and other comorbidities, VI showed higher risk for all the type of dementia (p < 0.0001). In subgroup analysis of VI, young males showed the highest risk for development of dementia with a HR of 2.687 (95% CI 2.219–3.254, p < 0.0001). VI significantly increased the risk of dementia in the study cohort, and young males with VI appeared to be the most susceptible to the development of dementia.

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Living Alone and Dementia Incidence: A Clinical-Based Study in People With Mild Cognitive Impairment

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/0891988718774425 ◽

2018 ◽

Vol 31 (3) ◽

pp. 107-113 ◽

Cited By ~ 11

Author(s):

Giulia Grande ◽

Davide Liborio Vetrano ◽

Ilaria Cova ◽

Simone Pomati ◽

Daniele Mattavelli ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Ad Hoc ◽

Cox Regression ◽

Population Based ◽

Living Alone ◽

Living Situation ◽

Hazard Ratios ◽

Dementia Incidence

Introduction: Social isolation and living alone have been associated with negative outcomes, especially in the older population. We aim to investigate the effect of living alone on the development of dementia in people with mild cognitive impairment (MCI). Materials and Methods: In this longitudinal study, we enrolled 345 outpatients with MCI evaluated at baseline through a clinical and neuropsychological protocol. Data on living situation (living alone vs. living with someone) were also collected. The development of dementia at follow-up was the outcome of the study. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression analyses. Laplace regression was used to model the time-to-dementia diagnosis as a function of living situation. Results: During the follow-up time (mean [SD]: 2.8 [2.2] years), 172 (50%) participants developed dementia. After controlling for age, sex, years of education, MCI subtype, presence of comorbidities, and antidepressant therapy, people with MCI living alone were more likely to develop dementia (HR: 1.5; 95% CI: 1.1-2.1), when compared to those living with someone. In addition, participants with MCI living alone were diagnosed with dementia 1 year earlier than those living with someone ( P = .012). Conclusion: Living alone increases by 50% the risk of developing dementia and anticipates by 1 year the diagnosis in people with MCI. These results, in line with findings of previous population-based studies, emphasize the pivotal role of the living situation in identifying a frailer share of the population at higher risk of dementia to which devote ad hoc assessment and care.

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Hospital volume of esophageal cancer surgery in relation to outcomes from primary anti-reflux surgery

Diseases of the Esophagus ◽

10.1093/dote/doaa075 ◽

2020 ◽

Author(s):

Sheraz Markar ◽

Giola Santoni ◽

John Maret-Ouda ◽

Jesper Lagergren

Keyword(s):

Esophageal Cancer ◽

Hospital Volume ◽

Cox Regression ◽

Population Based ◽

Cancer Surgery ◽

Esophageal Cancer Surgery ◽

Hazard Ratios ◽

Volume Group ◽

Annual Volume

Summary No previous study has sought to identify the effect of hospital volume of esophagectomy on anti-reflux surgery outcomes. The hypothesis under investigation was hospitals performing esophagectomies, particularly those of higher annual volume, have better outcomes from primary anti-reflux surgery. This population-based cohort study included adult individuals (≥18 years) in Sweden receiving primary anti-reflux surgery for a recorded gastro-esophageal reflux disease in 1997–2010, with follow-up until 2013 The ‘exposure’ was hospital volume of esophagectomy, with hospitals conducting esophagectomies divided into 0, >0–1, >1–3 and ≥ 4 based on annual volume, and hospitals not conducting esophagectomies were the reference category. The outcomes were 30-day re-intervention and surgical re-intervention during the entire follow-up after anti-reflux surgery. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for age, sex, comorbidity, type of anti-reflux surgery, and year of anti-reflux surgery. Among 10,959 participants having undergone primary anti-reflux surgery, the 30-day re-intervention rate was 1.1%, and the rate of surgical re-intervention during the entire follow-up was 6.8%. Compared with hospitals not performing esophagectomy, hospitals in the highest volume group of esophagectomy showed no decreased risks of 30-day re-intervention (HR = 1.46, 95% CI 0.89–2.39) or surgical re-intervention (HR = 1.21, 95%CI 0.91–1.60) during follow-up. Similarly, the intermediate hospital volume categories of esophageal cancer surgery had no decreased risk of surgical re-interventions after anti-reflux surgery. This study provides no evidence for centralization of primary anti-reflux surgery to centers for esophageal cancer surgery.

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Migraine as a predictor of mortality: The HUNT study

Cephalalgia ◽

10.1177/0333102415593090 ◽

2015 ◽

Vol 36 (4) ◽

pp. 351-357 ◽

Cited By ~ 9

Author(s):

Anders Nikolai Åsberg ◽

Lars Jacob Stovner ◽

John-Anker Zwart ◽

Bendik Slagsvold Winsvold ◽

Ingrid Heuch ◽

...

Keyword(s):

Cohort Study ◽

Cardiovascular Mortality ◽

Cox Regression ◽

Population Based ◽

Risk Of Death ◽

Hazard Ratios ◽

All Cause Mortality ◽

Large Prospective Cohort Study ◽

Migrainous Headache

Background There is conflicting evidence for the association between migraine and increased mortality risk. The aim of this study was to investigate the relationship between migraine and non-migrainous headache, and all-cause mortality and cardiovascular mortality. Methods In this prospective population-based cohort study from Norway, we used baseline data from the second Nord-Trøndelag Health Survey (HUNT2), performed between 1995 and 1997 in the County of Nord-Trøndelag. These data were linked with a comprehensive mortality database with follow-up through the year 2011. A total of 51,853 (56% of invited) people were categorized based on their answers to the headache questions in HUNT2 (headache free, migraine or non-migrainous headache). Hazard ratios (HRs) of mortality during a mean of 14.1 years of follow-up were estimated using Cox regression. Results During the follow-up period 9408 died, 4321 of these from cardiovascular causes. There was no difference in all-cause mortality between individuals with migraine and non-migrainous headache compared to those without headache or between headache status and mortality by cardiovascular disease. There was, however, among men with migraine without aura a reduced risk of death by cardiovascular diseases (HR 0.72, 95% confidence interval 0.56–0.93). This relationship was not evident in women. Conclusion In this large, prospective cohort study there was no evidence for a higher all-cause mortality or cardiovascular mortality among individuals with migraine.

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Mediterranean Diet Reduces Risk of Incident Stroke in a Population With Varying Cardiovascular Disease Risk Profiles

Stroke ◽

10.1161/strokeaha.117.020258 ◽

2018 ◽

Vol 49 (10) ◽

pp. 2415-2420

Author(s):

Katherine E. Paterson ◽

Phyo K. Myint ◽

Amy Jennings ◽

Lucy K.M. Bain ◽

Marleen A.H. Lentjes ◽

...

Keyword(s):

Cardiovascular Disease ◽

High Risk ◽

Mediterranean Diet ◽

Cox Regression ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Population Based ◽

Framingham Risk ◽

First Time

Background and Purpose— Although some evidence has found that the Mediterranean diet (MD) is protective for stroke risk, few studies have investigated whether this relationship differs by sex or cardiovascular disease risk. Methods— We investigated the relationship between adherence to the MD score, estimated using 7-day dietary diaries and risk of incident stroke in an observational prospective population-based cohort study of 23 232 men and women (54.5% women) aged 40 to 77 years who participated in the European Prospective Investigation into Cancer study in Norfolk, United Kingdom. Risk of incident stroke was calculated using multivariable Cox regression, in the whole population, and also stratified by sex and cardiovascular disease risk profile, using the Framingham risk score. Results— During 17.0 years of follow-up (395 048 total person-years), 2009 incident strokes occurred. Risk of stroke was significantly reduced with greater adherence to the MD score (quartile 4 versus quartile 1 hazard ratio [HR], 0.83; 95% CI, 0.74–0.94; P -trend <0.01) in the whole population and in women (quartile 4 versus quartile 1 HR, 0.78; 95% CI, 0.65, 0.93; P -trend <0.01) but not in men (quartile 4 versus quartile 1 HR, 0.94; 95% CI, 0.79–1.12; P -trend =0.55). There was reduced risk of stroke in those at high risk of cardiovascular disease and across categories of the MD score (quartile 4 versus quartile 1 HR, 0.87; 95% CI, 0.76–0.99; P -trend =0.04). However, this was driven by the associations in women (quartile 4 versus quartile 1 HR, 0.80; 95% CI, 0.65–0.97; P -trend =0.02). Conclusions— Greater adherence to the MD was associated with lower risk of stroke in a UK white population. For the first time in the literature, we also investigated the associations between the MD score in those at both low and high risk of cardiovascular disease. Although the findings in our study were driven by the associations in women, they have implications for the general public and clinicians for prevention of stroke.

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