Dementia, with Alzheimer's disease (AD) being the most common form, is a major hip fracture risk factor, but currently it is not known whether the same factors predict hip fracture among persons with and without dementia/AD. We compared the predictors of hip fracture and mortality after hip fracture in persons with and without AD.
An exposure-matched cohort of all community-dwellers of Finland who received a new clinically verified AD diagnosis in 2005-2011 and had no history of previous hip fracture (N = 67,072) and an age, sex, and region-matched cohort of persons without AD (N = 67,072). Associations between sociodemographic characteristics, comorbidities and medications and risk of hip fracture and mortality after hip fracture were assessed with Cox regression.
As expected, the incidence of hip fractures in 2005-2012 (2.19/100 person-years vs 0.90/100 person-years in the non-AD cohort), as well as mortality after hip fracture (29/100 person-years vs 23/100 person-years in the non-AD cohort) were higher in the AD cohort. This difference was evident regardless of the risk factors. Mental and behavioural disorders (adjusted hazard ratio; HR 95% confidence interval CI: 1.16, 1.09-1.24 and 1.71, 1.52-1.92 in the AD and non-AD-cohorts), antipsychotics (1.12, 1.04-1.20 and 1.56, 1.38-1.76 for AD and non-AD-cohorts) and antidepressants (1.06, 1.00-1.12 and 1.34 1.22-1.47 for AD and non-AD-cohorts) were related to higher, and estrogen/combination hormone therapy (0.87, 0.77-0.9 and 0.79, 0.64-0.98 for AD and non-AD-cohorts) to lower hip fracture risk in both cohorts. Stroke (1.42, 1.26-1.62), diabetes (1.13, 0.99-1.28), active cancer treatment (1.67, 1.22-2.30), proton pump inhibitors (1.14, 1.05-1.25), antiepileptics (1.27, 1.11-1.46) and opioids (1.10, 1.01-1.19) were associated with higher hip fracture risk in the non-AD cohort. Similarly, the associations between mortality risk factors (age, sex, several comorbidities and medications) were stronger in the non-AD cohort.
AD itself appears to be such a significant risk factor for hip fracture, and mortality after hip fracture, that it overrules or diminishes the effect of other risk factors. Thus, it is important to develop and implement preventive interventions that are suitable and effective in this population.
To study how long antidepressants initiated after diagnoses of Alzheimer's disease (AD) were used and factors associated with discontinuation of use among persons with Alzheimer's disease (AD). In addition, differences in duration of use between the antidepressants groups were compared.
Register-based Medication use and Alzheimer's disease (MEDALZ) cohort included 70,718 community-dwelling people with AD who were diagnosed during the years 2005-2011. For this study, the new antidepressant users were included after 1-year washout period (N?=?16,501; 68.6% females, mean age 80.9). The duration of antidepressant use was modeled with the PRE2DUP method. Factors associated with treatment discontinuation were assessed with Cox proportional hazard models and included age, gender, comorbid conditions and concomitant medications.
Median duration of the new antidepressant use period was 309 days (IQR 93-830). For selective serotonin reuptake inhibitor (SSRI) use, the median duration was 331 days (IQR 101-829), for mirtazapine 202 days (IQR 52-635), and for serotonin and norepinephrine reuptake inhibitors (SNRIs) 134 days (IQR 37-522). After 1-year follow-up, 40.8% had discontinued antidepressant use, 54.6% after 2 years and 64.1% after 3 years. Factors associated with treatment discontinuation were age over 85, male gender, diabetes, and use of memantine, opioids, and antiepileptics whereas benzodiazepines and related drugs and antipsychotic use were inversely associated with discontinuation.
Antidepressants are used for long-term among people with AD. Need and indication for antidepressant use should be assessed regularly as evidence on their efficacy for behavioral and psychological symptoms of dementia is limited.
Persons with Alzheimer's disease (AD) are frequently hospitalized from infection-related causes. There are no previous studies investigating hospitalization associated with antibiotic initiation in persons with AD.
To investigate the frequency and risk of hospitalization associated with oral antibiotic initiation among community dwellers with and without AD.
We performed a retrospective register-based study utilizing register-based Medication Use and Alzheimer's disease (MEDALZ) cohort. It includes all community dwellers diagnosed with AD during 2005-2011 in Finland and their matched comparison persons without AD. Antibiotic use was initiated by 34,785 persons with and 36,428 without AD. Drug use data were collected from Prescription Register and comorbidities from Special Reimbursement and Hospital Care Registers. Infection diagnoses were collected from the Hospital Care Register. Factors associated with hospitalization were estimated utilizing logistic regression models.
Risk of hospitalization following antibiotic initiation was higher among antibiotic initiators with AD than without AD (adjusted odds ratio, aOR, 1.37, 95% Cl 1.28-1.46).Strongest association with hospitalization was found for oral glucocorticoid use, aOR 1.41 (1.25-1.59); epilepsy, aOR 1.33 (1.10-1.63); and active cancer, aOR 1.30 (1.14-1.49). Among initiators of cephalexin, pivmecillinam, amoxicillin/amoxicillin, and enzyme inhibitor and doxycycline, persons with AD were more frequently hospitalized than persons without AD. A quarter of hospitalized antibiotic initiators had infection diagnosis in their hospital care records.
Persons with AD initiating an antibiotic had a higher risk for hospitalization than antibiotic initiators without AD. Further research is needed to determine whether infection-related hospitalization could be reduced.
ABSTRACTBackground:We analyzed the impact of opioid initiation on the prevalence of antipsychotic and benzodiazepine and related drug (BZDR) use among community-dwelling persons with Alzheimer's disease (AD).
We utilized the register-based Medication use and Alzheimer's disease (MEDALZ) cohort for this study. We included all community-dwelling persons diagnosed with AD during 2010-2011 in Finland initiating opioid use (n = 3,327) and a matched cohort of persons not initiating opioids (n = 3,325). Interrupted time series analyses were conducted to compare the prevalence of antipsychotic and BZDR use in 30-day periods within six months before opioid initiation to 30-day periods six months later.
Before opioid initiation, prevalence of antipsychotic use among opioid initiators was 13.3%, 18.3% at opioid initiation, and 17.3% six months later. Prevalences of BZDR use were 27.1% six months prior, 28.9% at opioid initiation, and 26.9% six months later. After opioid initiation, antipsychotic and BZDR use declined by 0.3 percentage points (pps, 95% confidence interval 0.1-0.5) and 0.4 pps (0.2-0.7) per month, respectively, until the end of the follow-up. Compared to persons not initiating opioid use, opioid initiation immediately resulted in an increase in prevalence of 1.9 pps (0.9-2.8) for antipsychotics and of 1.6 pps (0.9-2.2) for BZDR use. However, in total there was a comparative decrease of 0.5 pps (0.3-0.8) per month for antipsychotics and of 0.4 pps (0.2-0.6) for BZDR use until the end of the follow-up.
Our results suggest that opioid initiation may reduce antipsychotic and BZDR use among persons with AD.
The study aimed to investigate the incidence of antidepressant use in persons with and without Alzheimer's disease (AD) from 9?years before to 4?years after AD diagnosis and to examine the incidence of different antidepressant groups.
We used register-based data from the Medication use and Alzheimer's disease cohort including all Finnish persons diagnosed with AD in 2005-2011 with their age-matched and gender-matched comparison persons without AD. In this study, 62,104 persons with AD and 62,104 comparison persons were included. Data on dispensed antidepressants during 1995-2012 were collected from the Prescription Register. A 1-year washout period was utilized to measure the rate of new antidepressant users every 6-month period starting from 9?years before and until 4?years after the AD diagnoses. The incidence rate between persons with and without AD was compared with Poisson regression.
The incidence of antidepressant use in persons with AD was higher during the whole study period compared with that in persons without AD. The incidence rate was highest at 6?months after AD diagnosis (incidence rate ratio?=?5.22, 95% confidence interval 4.77-5.72). Selective serotonin reuptake inhibitors were the most frequently initiated group (61.3% of initiations in persons with AD).
The objective of this study was to investigate whether incident opioid use is associated with an increased risk of hip fractures among community-dwelling persons with Alzheimer disease (AD) and to assess the association in terms of duration of use and opioid strength. Among community-dwelling persons with AD diagnosed in 2010 to 2011 (N = 23,100), a matched cohort study comparing incident opioid users (N = 4750) with opioid nonusers (N = 4750) was constructed. Matching was based on age, sex, and time since AD diagnosis at opioid initiation. Data on drug use and hip fractures were retrieved from nationwide registers. Incident opioid users were identified with a 1-year washout. Cox proportional hazard models compared the risk of hip fracture between opioid use and nonuse, and were weighted with inverse probability of treatment (IPT), based on a propensity score. Age-adjusted incidence rate of hip fractures was 3.47 (95% confidence interval [CI] 2.62-4.33) during opioid use and 1.94 (95% CI 1.65-2.22) during nonuse. Opioid use was associated with an increased risk of hip fracture (IPT-weighted hazard ratio [HR] 1.96, 95% CI 1.27-3.02). The risk was observed during the first 2 months of use (IPT-weighted HR 2.37, 1.04-5.41) and attenuated after that. The results suggest an increase in the risk of hip fracture by increasing opioid strength; weak opioids IPT-weighted HR 1.75 (0.91-3.35), buprenorphine IPT-weighted HR 2.10 (1.41-3.13), and strong opioids IPT-weighted HR 2.89 (1.32-6.32). Further research is needed to find out whether the risk of injurious falls is avoidable by slow titration of opioid doses in the beginning of treatment.
The aim of this study was to investigate the prevalence of benzodiazepine and related drug (BZDR) use, especially long-term use, and associated factors among community-dwelling individuals with and without Alzheimer's disease (AD). We utilized data from the MEDALZ-2005 cohort, which includes all community-dwelling individuals diagnosed with AD in Finland at the end of 2005 and matched comparison individuals without AD. Register-based data included prescription drug purchases, comorbidities, and hospital discharge diagnoses. In this study, 24,966 individuals with AD and 24,985 individuals without AD were included. During the 4-year follow-up, we found that 45% (N = 11,312) of individuals with AD and 38% (N = 9534) of individuals without AD used BZDRs. The prevalence of long-term (= 180 days) BZDR use was more common among individuals with AD (30%) than individuals without AD (26%). The median durations of the first long-term use periods of BZDRs were 1.5 and 2 years for individuals with and without AD, respectively. Factors associated with long-term BZDR use included female sex, AD, schizophrenia, bipolar disorder, depression, coronary artery disease, and asthma/chronic obstructive pulmonary disease. The high prevalence of long-term BZDR use among individuals with AD is especially a cause for concern because long-term use may further impair cognition and may be associated with serious adverse events.
Persons with Alzheimer disease (AD) commonly present with chronic nonmalignant pain, but long-term use of opioids among this population has not been studied previously. Our aim was to investigate the prevalence of long-term (=180 days) use of opioids for nonmalignant pain and associated factors among community-dwelling persons with AD and to compare the prevalence with a matched cohort without AD. The Medication use and Alzheimer's disease (MEDALZ) cohort was used for this study, comprising all community-dwelling persons diagnosed with AD in Finland during 2005 to 2011 and their matched comparison persons without AD. After exclusion of persons with active cancer treatment, 62,074 persons with and 62,074 persons without AD were included in this study. Data were collected from nationwide registers. Opioids were used by 13,111 persons with and by 16,659 without AD. Overall long-term opioid use was more common among persons without AD (8.7%) than among persons with AD (7.2%, P
The aim of this study is to determine the prevalence of use and long-term use (=180 days) of proton pump inhibitors (PPIs) and associated factors among community-dwellers with and without Alzheimer's disease (AD).
MEDALZ cohort encompassed all persons who received a verified diagnosis of AD in Finland during the years 2005-2011 and their age-, sex-, and region of residence-matched comparison persons, including 69,353 persons with and 69,353 persons without AD. Data was derived from several Finnish administrative registers. A mathematical modelling method, PRE2DUP, was used for converting dispensing data to drug use periods (when regular PPI use started and ended). Morbid conditions and concomitant drugs associated with use and long-term use of PPIs were assessed with logistic regression models.
Use of PPIs was more common among comparison persons than persons with AD (39.0 and 35.8%, respectively, p
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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.
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