Project description:PurposeGlaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort.DesignNational matched cohort study.ParticipantsA total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia.MethodsCox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for sociodemographic factors and comorbidities.Main outcome measuresAlzheimer's disease, VaD, and all-cause dementia identified from nationwide inpatient and outpatient diagnoses through 2018.ResultsIn 16 million person-years of follow-up, 32 339 persons (10%) with glaucoma and 226 896 controls (7%) were diagnosed with dementia. Persons with glaucoma had increased risks for AD (adjusted HR, 1.39; 95% confidence interval [CI], 1.35-1.43), VaD (1.66; 1.61-1.72), and all-cause dementia (1.57; 1.54-1.59). Among glaucoma subtypes, both primary open-angle and normal-tension glaucoma were associated with increased risk for AD (adjusted HR, 1.31; 95% CI, 1.27-1.36; and 1.28; 1.20-1.36, respectively) and VaD (1.61; 1.54-1.68; and 1.39; 1.28-1.50, respectively), whereas primary angle-closure glaucoma was associated with VaD (1.26; 1.02-1.56) but not AD (0.98; 0.82-1.18). These findings were similar in men and women. All risks were highest in persons diagnosed with glaucoma at ages ≥ 70 years and were not elevated for ages < 60 years.ConclusionsIn this large national cohort, persons with glaucoma had increased risks for AD, VaD, and all-cause dementia, particularly those diagnosed with glaucoma at older ages. Persons with glaucoma may need increased monitoring for dementia to facilitate earlier detection and treatment.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Project description:BackgroundPneumonia is a very common infection in the cognitively impaired adult population, often leading to long-term deterioration, in physical and cognitive performance. Evidence is lacking on whether chronic comorbidities and drug use are risk factors for pneumonia in persons with Alzheimer's disease (AD). The objective of this study was to investigate the risk factors of pneumonia in community dwellers with and without AD.MethodsWe performed a retrospective register-based study utilizing the Medication Use and Alzheimer's disease (MEDALZ) cohort, which is based on Finnish nationwide healthcare registers and includes all community dwellers who received a verified clinical diagnosis of AD between 2005 to 2011. This study comprised 69,350 persons with AD and 69,350 persons without AD matched by age, gender, and region of residence. Association between comorbidities, drug use, and hospitalization due to pneumonia were assessed using Cox Regression.ResultsDuring the follow-up, 25.0% (n = 17,105) of the AD cohort and 15.8% (n = 10,966) of the non-AD cohort were hospitalized due to pneumonia. Persons with AD had a higher risk of pneumonia also after adjusting for comorbidities (HR 1.76, 95% CI 1.71-1.80). Previous pneumonia was the strongest risk factor for pneumonia in both cohorts. All comorbidities and drug use excluding biological product use were associated with a higher risk of pneumonia, but stronger associations were observed in the non-AD cohort. The risk of hospitalization following psychotropic drug use was proportional to the number of psychotropics utilized.ConclusionsPneumonia is a serious, potentially life-threatening illness, and risk factors for pneumonia include several potentially avoidable drugs. In addition, good care of existing comorbidities might prevent pneumonia and related hospitalization.
Project description:AimsPreterm birth has been associated with elevated blood pressure early in life; however, hypertension risks from childhood into adulthood remain unclear. We conducted a large population-based study to examine gestational age at birth in relation to hypertension risks from childhood into adulthood.Methods and resultsA national cohort study was conducted of all 4 193 069 singleton live births in Sweden during 1973-2014, who were followed up for hypertension identified from nationwide inpatient and outpatient (specialty and primary care) diagnoses from any health care encounters through 2015 (maximum age 43 years; median 22.5). Cox regression was used to examine gestational age at birth in relation to hypertension risk while adjusting for other perinatal and maternal factors, and co-sibling analyses assessed the potential influence of unmeasured shared familial (genetic and/or environmental) factors. In 86.8 million person-years of follow-up, 62 424 (1.5%) persons were identified with hypertension (median age 29.8 years at diagnosis). Adjusted hazard ratios for new-onset hypertension at ages 18-29 years associated with preterm (<37 weeks) and extremely preterm (22-27 weeks) birth were 1.28 [95% confidence interval (CI), 1.21-1.36] and 2.45 (1.82-3.31), respectively, and at ages 30-43 years were 1.25 (1.18-1.31) and 1.68 (1.12-2.53), respectively, compared with full-term birth (39-41 weeks). These associations affected males and females similarly and appeared substantially related to shared genetic or environmental factors in families.ConclusionsIn this large national cohort, preterm birth was associated with increased risk of hypertension into early adulthood. Persons born prematurely may need early preventive evaluation and long-term monitoring for the development of hypertension.
Project description:ObjectiveHearing impairment is suggested to be associated with depression in the elderly. The present study evaluated the risk of depression after hearing impairment in all age groups matched by age, sex, income, and region of residence.MethodsThe Korean Health Insurance Review and Assessment Service-National Patient Samples were collected for a period from 2002 to 2013. Hearing impairment was defined as a hearing threshold ≥ 60 dB in both ears or as ≥ 80 dB in one ear and ≥ 40 dB in one ear. Hearing-impaired participants performed a pure tone audiometry test 3 times and an auditory brainstem response threshold test once. The 6,136 hearing-impaired participants were matched 1:4 with 24,544 controls with no reported hearing impairment for age, sex, income, and region of residence. Depression was investigated based on the International Classification of Disease-10 codes F31 (bipolar affective disorder) through F39 (unspecified mood disorder) by a psychiatrist from 2002 through 2013. The crude (simple) and adjusted (age, sex, income, region of residence, dementia, hypertension, diabetes, and dyslipidemia) hazard ratio (HR) of hearing impairment on depression were analyzed using Cox-proportional hazard model.ResultsThe rate of depression was significantly higher in the severe hearing-impaired group than in the control group (7.9% vs. 5.7%, P < 0.001). Severe hearing impairment increased the risk of depression (adjusted HR = 1.37, 95% confidence interval [CI] = 1.24-1.52, P < 0.001). In a subgroup analysis, young (0-29 years old), middle-aged (30-59 years old), and old (≥ 60 years old) severe hearing-impaired groups showed significantly increased risk of depression compared to controls with no reported hearing impairment. In accordance with income level, severe hearing impairment elevated depression in the low and high income groups, but not in the middle income group.ConclusionSevere hearing impairment increased the risk of depression independently of age, sex, region, past medical histories, and income (in low and high income persons but not in middle income persons).
Project description:Antidepressant use has been associated with an increased risk of falling, but no studies have been conducted on whether antidepressant use is associated with an increased risk of head injuries which often result from falling among older persons. The objective of this study was to investigate the risk of head and brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer's disease.A matched cohort study was conducted by comparing new antidepressant users (n = 10,910) with two matched nonusers (n = 21,820) in the MEDALZ study cohort. The MEDALZ cohort includes all community-dwelling persons newly diagnosed with Alzheimer's disease between 2005 and 2011 in Finland. Incident antidepressant users were identified based on register-based dispensing data from the Prescription register with a 1-year washout period for antidepressant use. Nonusers were matched with users based on age, gender, and time since Alzheimer's disease diagnosis. The outcome events were defined as any head injuries and traumatic brain injuries based on diagnoses in Hospital Discharge and Causes of Death registers. Propensity score adjusted Cox proportional hazard models were utilized. Sensitivity analyses with case-crossover design were conducted. All registers are linkable with unique personal identification numbers assigned for each resident.Antidepressant use was associated with an increased risk of head injuries (age-adjusted event rate per 100 person-years 2.98 (95% confidence interval (CI) 2.49-3.06) during use and 2.43 (95% CI 2.06-2.35) during nonuse, adjusted hazard ratio (HR) 1.35, 95% CI 1.20-1.52) and traumatic brain injuries (age-adjusted event rate per 100 person-years 1.33 (95% CI 1.13-1.53) during use and 1.10 (95% CI 1.00-1.20) during nonuse, adjusted HR 1.26, 95% CI 1.06-1.50). The risk was highest during the first 30 days of use (HR 1.71, 95% CI 1.10-2.66 for head injuries; HR 2.06, 95% CI 1.12-3.82 for traumatic brain injuries) and remained at an elevated level for head injuries for over 2 years of use. In case-crossover analyses, antidepressant use was consistently associated with a higher risk of head injuries.Antidepressant use was associated with an increased risk of the most severe outcomes, head and brain injuries, in persons with Alzheimer's disease. Antidepressant use should be carefully considered and the association confirmed in future studies.
Project description:IntroductionTo examine the risk of Alzheimer's disease (AD) among cancer survivors in a national database.MethodsRetrospective cohort of 3,499,378 mostly male US veterans aged ≥65 years were followed between 1996 and 2011. We used Cox models to estimate risk of AD and alternative outcomes (non-AD dementia, osteoarthritis, stroke, and macular degeneration) in veterans with and without a history of cancer.ResultsSurvivors of a wide variety of cancers had modestly lower AD risk, but increased risk of the alternative outcomes. Survivors of screened cancers, including prostate cancer, had a slightly increased AD risk. Cancer treatment was independently associated with decreased AD risk; those who received chemotherapy had a lower risk than those who did not.DiscussionSurvivors of some cancers have a lower risk of AD but not other age-related conditions, arguing that lower AD diagnosis is not simply due to bias. Cancer treatment may be associated with decreased risk of AD.
Project description:BackgroundDepression and the increased risk of sarcopenia are prevalent among the elderly population. However, the causal associations between these factors remain unclear. To investigate the potential association between depression and the risk of sarcopenia in older adults, this study was performed.MethodsIn the baseline survey, a total of 14,258 individuals aged 40 and above from the China Health and Retirement Longitudinal Study (2015) participated. We initially described the baseline prevalence of the disease. Then, logistic regression and restricted cubic spline (RCS) regression were conducted to assess the relationship between depression and sarcopenia. Subgroup analysis was performed to validate the robustness of the findings. Additionally, we conducted Mendelian randomization analysis using the inverse variance weighting estimator to assess the causal relationship between depression and sarcopenia. Furthermore, we adopted six methods, including MR-Egger, simple median, weighted median, maximum likelihood, robust adjusted profile score (RAPS), and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), for sensitivity analyses.ResultsDepression patients exhibited higher risks of sarcopenia in all five models adjusting for different covariates (P < 0.05). The RCS analysis demonstrated a linear relationship between depression and sarcopenia (P < 0.05). In the subgroup analysis, increased risk was observed among participants aged 60-70, married or cohabiting individuals, non-smokers, non-drinkers, those with less than 8 h of sleep, BMI below 24, and individuals with hypertension (all P < 0.05). Mendelian randomization results revealed that genetically proxied depression led to a reduction in appendicular skeletal muscle mass (all P < 0.05).ConclusionOur study provides observational and causal evidences that depression can lead to sarcopenia. This finding emphasizes the importance of timely identification and management of depression, as well as implementing targeted educational programs as part of comprehensive strategies to prevent sarcopenia.
Project description:BackgroundAntiepileptic drugs (AEDs) have sedative properties which may lead to an increased risk of pneumonia.ObjectivesTo investigate whether incident AED use is associated with an increased risk of pneumonia among community-dwelling persons with Alzheimer's disease (AD). In addition, we determined the risk according to duration of AED use and specific AEDs.MethodsPersons with AD were identified from the MEDALZ dataset which includes all community-dwelling persons who received a clinically verified diagnosis of AD during 2005-2011 in Finland (N=70,718). New AED users were identified with one-year washout period. A matched cohort (1 : 1, N=5,769, matching criteria age, gender, and time since AD diagnoses) of nonusers was formed. Data from nationwide registers included dispensed medications which were modelled with PRE2DUP method, hospitalizations, and causes of death. The association between AED use and hospital admission or death due to pneumonia was analyzed with Cox proportional hazard models.ResultsAED use was associated with an increased risk of pneumonia (adjusted HR 1.92, 95% CI 1.63-2.26; incidence rate per 100 person-years 12.58, 95% CI 12.49-12.66 during AED use and 6.41, 95% CI 6.37-6.45 during nonuse). The highest risk was observed during the first month of use (aHR 3.59, 95% CI 2.29-5.61) and the risk remained elevated until two years of use. Of specific drug substances, phenytoin, carbamazepine, valproic acid, and pregabalin were associated with an increased risk.ConclusionAntiepileptic drug use may increase the risk of pneumonia which is concerning as persons with AD have elevated risk of pneumonia.
Project description:BackgroundAlzheimer's disease (AD) is one of the leading causes of death world-wide, but little is known on the role of comorbidities on mortality among people with AD. We studied how comorbidities and age at AD diagnosis impact the survival of people with AD.MethodsThe Medication Use and Alzheimer's disease (MEDALZ) cohort study included 70,718 community-dwelling persons in Finland with AD diagnosis from 2005 to 2011 and were matched 1:1 (age, gender, and hospital district) to people without AD (mean age 80 years, 65% women, and the mean follow-up 4.9 and 5.6 years, respectively). Covariates (age, gender, and socioeconomic position), comorbidities (cardiovascular disease, stroke, diabetes, asthma/ chronic obstructive pulmonary disease (COPD), hip fracture, cancer treatment, and mental or behavioral disorders excluding dementia) and survival data were obtained from nationwide registers. Cox proportional hazard models were used to compare risk of death between people with and without AD.ResultsDuring the follow-up period a greater proportion of the AD cohort died compared to the non-AD cohort (63% versus 37%). In both cohorts, older age, male gender, lower socioeconomic position, and history of comorbidities were associated with shorter survival and higher risk of death. The associations of comorbidities with survival is weaker in the older age groups and people with AD. Hip fracture (adjusted HR 1.35, 95% CI 1.30-1.41), stroke (1.30, 1.27-1.34), and recent cancer treatment (1.29, 1.26-1.32) had the strongest associations in the AD cohort. Age modified the associations in both cohorts (weaker associations among older people).ConclusionAlzheimer's disease is the major factor affecting survival, but comorbidities further decrease survival also in individuals with Alzheimer's disease. Therefore, appropriate management of care of these comorbidities might affect not only survival but also the wellbeing of this vulnerable population.
Project description:IntroductionAlthough the association between Alzheimer's disease (AD) and constipation is controversial, its causality and underlying mechanisms remain unknown.ObjectivesTo investigate the potential association between slow gut transit and AD using epidemiological data and a murine model.MethodsWe conducted a bi-national cohort study in South Korea (discovery cohort, N=3,130,193) and Japan (validation cohort, N=4,379,285) during the pre-observation period to determine the previous diagnostic history (2009-2010) and the follow-up period (2011-2021). To evaluate the causality, we induced slow gut transit using loperamide in 5xFAD transgenic mice. Changes in amyloid-beta (Aβ) and other markers were examined using ELISA, qRT-PCR, RNA-seq, and behavioral tests.ResultsConstipation was associated with an increased risk of AD in the discovery cohort (hazard ratio, 2.04; 95% confidence interval [CI], 2.01-2.07) and the validation cohort (hazard ratio; 2.82; 95% CI, 2.61-3.05). We found that loperamide induced slower gut transit in 5xFAD mice, increased Aβ and microglia levels in the brain, increased transcription of genes related to norepinephrine secretion and immune responses, and decreased the transcription of defense against bacteria in the colonic tissue.ConclusionImpaired gut transit may contribute to AD pathogenesis via the gut-brain axis, thus suggesting a cyclical relationship between intestinal barrier disruption and Aβ accumulation in the brain. We propose that gut transit or motility may be a modifiable lifestyle factor in the prevention of AD, and further clinical investigations are warranted.