Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders.

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.

ß2-Adrenoceptor Agonists in Asthma or Chronic Obstructive Pulmonary Disease and Risk of Parkinson's Disease: Nested Case-Control Study.

Introduction: Although ß2-adrenoceptor (ß2AR) agonists have been associated with a lower risk of Parkinson's disease (PD), the findings are inconclusive and may reflect confounding by indication. We studied the association between inhaled ß2AR agonists and risk of PD in persons with asthma or chronic obstructive pulmonary disease (COPD). Methods: The nested case-control study was conducted within a register-based Finnish Parkinson's disease study (FINPARK) and included 1406 clinically verified PD cases diagnosed during 1999-2015, who also had asthma/COPD >3 years before PD. PD cases were matched with up to seven controls by age, sex, duration of asthma/COPD, pulmonary diagnosis, and region (N = 8630). Cumulative and average annual exposure to short- and long-acting ß2AR agonists before a 3-year lag period was assessed with quartiles of defined daily doses (DDDs). Adjusted odds ratios (aORs) were calculated with 95% confidence intervals (CIs) using conditional logistic regression. Results: Cumulative exposure to either short- or long-acting ß2AR agonists was not associated with a risk of PD. With average annual exposure, a decreased risk was observed only for the highest quartile of long-acting ß2AR agonists (aOR 0.75; 95% CI 0.58-0.97). In the stratified analysis the lowest risk estimates were observed among those with both asthma and COPD diagnoses. The suggestion of an inverse association was seen for the highest quartile of long-acting ß2AR agonists in asthma. Discussion: Higher levels of exposure to ß2AR agonists were not consistently associated with a reduced risk of PD. The inverse association in the highest category of average annual exposure to long-acting ß2AR agonists may be explained by unmeasured confounding, such as disease severity or smoking.

Real-world effectiveness of antidepressant use in persons with schizophrenia: within-individual study of 61,889 subjects.

The aim of this study was to investigate the real-world effectiveness of antidepressant use in persons with schizophrenia. The register-based study cohort included all 61,889 persons treated in inpatient care due to schizophrenia during 1972-2014 in Finland. The main outcome was hospitalization due to psychosis and secondary outcomes included non-psychiatric hospitalization and all-cause mortality. We used within-individual design to compare the risk of hospitalization-based outcomes during the time periods of antidepressant use to antidepressant non-use periods within the same person, and traditional between-individual Cox models for mortality. The risk of psychosis hospitalization was lower during antidepressant use as compared to non-use (adjusted Hazard Ratio, aHR, 0.93, 95% CI 0.92-0.95). Antidepressants were associated with a decreased risk of mortality (aHR 0.80, 95% CI 0.76-0.85) and a slightly increased risk of non-psychiatric hospitalization (aHR 1.03, 95% CI 1.01-1.06). In conclusion, these results indicate that antidepressants might be useful and relatively safe to use in this population.

The Cumulative Use of Muscle Relaxants and the Risk of Alzheimer's Disease: A Nationwide Case-Control Study.

BACKGROUND: Use of pharmacological treatments is one possible modifiable risk factor for cognitive disorders. OBJECTIVE: To investigate if the use of muscle relaxants is associated with the risk of Alzheimer's disease (AD). METHODS: The study was performed in a nested case-control design. Altogether 70,718 community-dwelling residents of Finland who received AD diagnosis in 2005-2011 were included as cases (the MEDALZ study). Each case was matched with four controls without AD by age, sex, and region of residence (N = 282,858). Data was extracted from Prescription register (1995-2012), Special Reimbursement register (1972-2012), and Hospital Discharge register (1972-2012). Drug use periods were modeled with PRE2DUP-method. Defined daily dose (DDD) was used to quantify the use. Analyses were conducted for any muscle relaxant use, and drug specific analyses were done for orphenadrine and tizanidine. A five-year lag window prior to the diagnosis was used, and results analyzed with conditional logistic regression. RESULTS: The use of any muscle relaxant was associated with the risk of AD, aOR (95% CI) 1.04 (1.02-1.07). Stronger associations were observed with longer use (>366 days, aOR 1.12 (1.03-1.21)) than shorter use (1-365 days aOR, 1.04 (1.02-1.06)) compared to non-users. Dose-response was not observed. Tizanidine was not associated with AD, whereas cumulative exposure of orphenadrine (≥101 DDDs) was associated with the risk of AD, aOR 1.19 (1.07-1.32). CONCLUSION: Muscle relaxant use was associated with the risk of AD and higher exposure to orphenadrine showed increased risk. Further studies on higher doses and longer durations of use are warranted.

Real-world effectiveness of mood stabilizer use in schizophrenia.

OBJECTIVE: Mood stabilizers (MS) are often used as adjunctive medication in patients with schizophrenia. The aim of this study was to investigate the real-world effectiveness of MS use in persons with schizophrenia. METHODS: The study cohort included all persons treated in inpatient care due to schizophrenia during 1972-2014 in Finland (N = 61,889). Drug purchase data were obtained from the national Prescription register and modeled with the PRE2DUP method. The follow-up period covered the years 1996-2017. Mood stabilizers included carbamazepine, valproic acid, lamotrigine, and lithium. The main outcome was psychosis hospitalization. We utilized within-individual design to compare the risk of outcome between time-periods of MS use and non-use within the same person. Stratified Cox regression analyses were conducted with adjusted hazard ratios (aHR) and 95% confidence intervals (CIs). RESULTS: Mean age at cohort entry was 46.2 years (SD 16.0) and 50.3% were male. During the follow-up (maximum of 22 years, median 14.8 years, interquartile range 7.5-22.0), 28.1% (N = 17,370) of the study cohort used MS, valproic acid being the most often used one (60.4%, N = 10,483). Risk of psychosis hospitalization was lower during MS use than non-use (aHR 0.88, 95% CI 0.86-0.90). Use of lithium (0.84, 0.81-0.87), valproic acid (0.87, 0.85-0.90), and lamotrigine (0.90, 0.85-0.95) were associated with lower risk of psychosis hospitalization compared with their non-use, whereas carbamazepine use was not. CONCLUSIONS: Mood stabilizers were relatively often used as adjunctive treatments in schizophrenia and their use was associated with a 12% decreased risk of psychosis rehospitalization, a marker of relapse in schizophrenia.

Recent Hospitalization and Initiation of Antiepileptics Among Persons With Alzheimer's Disease.

OBJECTIVES: Antiepileptic drugs (AEDs) are frequently prescribed for persons with Alzheimer's disease (AD), but little is known on factors associated with AED initiation in this population. We investigated whether recent hospitalization is associated with AED initiation in persons with AD. DESIGN: Nested case-control study in the nationwide register-based Medication use and Alzheimer's disease (MEDALZ) cohort. PARTICIPANTS AND SETTINGS: The MEDALZ cohort includes 70,718 persons diagnosed with AD during 2005-2011 in Finland. Altogether 6814 AED initiators and 6814 age-, sex-, and time since AD diagnosis-matched noninitiators were included in this study. Matching date was the date of AED initiation. METHODS: AED purchases were identified from the Prescription Register and hospitalizations from the Care Register for Health Care. Recent hospitalization was defined as hospitalization ending within 2 weeks before the matching date. Association between recent hospitalization and AED initiation was assessed with conditional logistic regression. RESULTS: The most frequently initiated AEDs were pregabalin (42.9%) and valproic acid (32.2%). A bigger proportion of AED initiators (36.9%) than noninitiators (5.3%) were recently hospitalized [odds ratio (OR) 10.5, 95% CI 9.22-11.9]. Dementia was the most frequent discharge diagnosis among AED initiators (29.1%) and noninitiators (27.9%). Among AED initiators, the next most frequent diagnosis was epilepsy (20.6%). Musculoskeletal diagnoses and use of analgesics including opioids was more common among gabapentinoid initiators compared with other AED initiators. CONCLUSIONS AND IMPLICATIONS: Recent hospitalization was significantly related to AED initiation. Initiations of AED might have been related to common symptoms in persons with AD like neuropathic pain, epilepsy, and neuropsychiatric symptoms.

Identification of Drugs Associated with Lower Risk of Parkinson's Disease Using a Systematic Screening Approach in a Nationwide Nested Case-Control Study.

Introduction: Drugs for other indications may be repurposable as disease-modifying drugs for Parkinson's disease (PD). A systematic hypothesis-free approach can enable identification of candidates for repurposing. We applied a hypothesis-free systematic approach to identify drugs associated with lower risk of PD to discover candidates with potential for repurposing as disease-modifying drugs for PD and to illustrate challenges in observational studies that simultaneously investigate multiple repurposing candidates. Methods: The Finnish Parkinson's disease study (FINPARK), a nationwide nested case-control study, was randomized to screening (10,183 cases, 67,849 controls) and replication (10,184 cases, 67,754 controls) samples, including cases diagnosed in 1998-2015. After screening all univariable associations of register-derived exposure to individual-drug, group- and subgroup level since 1995 (exposure ≥3 years before outcome, threshold P = 0.1), different exposure periods were used in confounder-adjusted replication analyses. Results: In screening stage, the group-level (antipsoriatics and antigout preparations) and subgroup-level (cicatrizants, topical antipsoriatics, antigout preparations and mydriatics and cycloplegics) associations were mainly due to individual drugs. Seven other drugs (eg methotrexate, drugs for chronic obstructive pulmonary disease, COPD and/or asthma) were associated with lower risk. Associations of antigout preparations and antipsoriatics were replicated. COPD/asthma drugs, methotrexate and diabetes drugs were studied in separate, indication-restricted designs. Discussion: The results reflect the known risk factors and the implied role of the immune system in PD pathogenesis and spurious associations. They underline the importance of controlling for confounding by indication, which is challenging to apply to systematic screening.

Incidence of antipsychotic use among community dwellers with and without Parkinson's disease.

INTRODUCTION: Previous studies have assessed antipsychotic use after Parkinson's disease (PD) diagnosis, but incident antipsychotic use before PD diagnosis is unknown. The objective is to study the incidence of antipsychotic use among community-dwelling persons with and without PD 10 years before and after the PD diagnosis. METHODS: The study was based on the nationwide register-based FINPARK-study including 20,994 persons with PD (diagnosed 1996-2015) and 142,944 comparison persons who had not used antipsychotics during one-year washout before the follow-up. PD was diagnosed according to the United Kingdom's Parkinson's disease Society Brain Bank's criteria. Antipsychotic initiations in six-month time-windows was assessed. RESULTS: 26.9% (n = 5,654) of people with PD initiated antipsychotics in comparison to 9.7% (n = 13,887) of people without PD during the entire follow-up. The incidence rate increased in people with PD approximately four years before the PD diagnosis. The most commonly initiated antipsychotic was quetiapine (n = 3,642, 64.4%) in persons with PD and risperidone (n = 5,232, 37.7%) in comparison persons. The initiation rates were higher in persons with PD before (6.5 and 3.0/1000 person-years for persons with and without PD, respectively, incidence rate ratio 2.18, 95%CI 2.03-2.33) and after the index date (43.3 and 11.7/1000 person-years for persons with and without PD, respectively, IRR 3.70, 95%CI 3.57-3.83). CONCLUSION: Persons with PD have symptoms treated with antipsychotics both before and after diagnosis. Psychotic symptoms may be challenging to recognize as prodromal symptoms since they can occur years before the motor symptoms and thus, they cannot be clinically associated with the diagnosis of PD.

Treatment initiation for parkinson's disease in Australia 2013-2018: a nation-wide study.

BACKGROUND: Guidelines highlight the importance of an individualized approach to treatment initiation for Parkinson's disease. Our aim was to investigate initiation of anti-Parkinson medication in Australia from 2013-2018, and to determine factors predicting choice of initial treatment. METHODS: Cohort of new-users (N = 4,887) of anti-Parkinson medication aged ≥ 40 years were identified from a 10% random representative sample of national medication dispensing data from July-2013 to June-2018. Changes in treatment initiation were examined across the whole cohort and stratified by age and sex. RESULTS: Treatment initiation was most frequent with levodopa followed by non-ergot dopamine agonists (DAs) and anticholinergics. Two thirds initiated with levodopa across the study period. Initiation with non-ergot DAs increased from 22 to 27% (rate ratio, RR 1.23, 95% confidence interval, CI 1.02-1.47) and initiation with anticholinergics decreased from 6.9% to 2.4% (RR 0.34, 95% CI 0.21-0.55) from 2013-2018. Among persons aged ≥ 65 years, one third of women and one fourth of men initiated on levodopa. Among women aged < 65 years, rates of treatment initiation with DAs (37%) and levodopa (37%) were similar in 2013/2014 but initiation with DA exceeded levodopa thereafter. Among men aged < 65 years, treatment initiation with levodopa (44%-49%) remained more frequent than initiation with DAs (29%-32%) throughout the study period. CONCLUSIONS: Treatment initiation with levodopa was most frequent among persons aged ≥ 65 years, consistent with current guidelines. Whilst the value of levodopa sparing strategies is unclear, treatment initiation with DA has become increasingly common relative to levodopa among women but not among men aged < 65 years.

Prevalence of oral anticoagulant use among people with and without Alzheimer's disease.

BACKGROUND: Although cardio- and cerebrovascular diseases are common among people with Alzheimer's disease (AD), it is unknown how the prevalence of oral anticoagulant (OAC) use changes in relation to AD diagnosis. We investigated the prevalence of OAC use in relation to AD diagnosis in comparison to a matched cohort without AD. METHODS: Register-based Medication use and Alzheimer's disease (MEDALZ) cohort includes 70 718 Finnish people with AD diagnosed between 2005-2011. Point prevalence of OAC use (prescription register) was calculated every three months with three-month evaluation periods, from five years before to five years after clinically verified diagnosis and compared to matched cohort without AD. Longitudinal association between AD and OAC use was evaluated by generalized estimating equations (GEE). RESULTS: OAC use was more common among people with AD until AD diagnosis, (OR 1.17; 95% CI 1.13-1.22), and less common after AD diagnosis (OR 0.87; 95% CI 0.85-0.89), compared to people without AD. At the time of AD diagnosis, prevalence was 23% and 20% among people with and without AD, respectively. OAC use among people with AD began to decline gradually two years after AD diagnosis while continuous increase was observed in the comparison cohort. Warfarin was the most common OAC, and atrial fibrillation was the most common comorbidity in OAC users. CONCLUSION: Decline in OAC use among people with AD after diagnosis may be attributed to high risk of falling and problems in monitoring. However, direct oral anticoagulants (DOACs) that are nowadays more commonly used require less monitoring and may also be safer for vulnerable people with AD.

Association between different diabetes medication classes and risk of Parkinson's disease in people with diabetes.

PURPOSE: Diabetes has been associated with increased risk of Parkinson's disease (PD). Diabetes medications have been suggested as a possible explanation, but findings have been inconsistent. More information on the role of exposure in different time windows is needed because PD has long onset. We assessed the association between use of different diabetes medication categories and risk of PD in different exposure periods. METHODS: A case-control study restricted to people with diabetes was performed as part of nationwide register-based Finnish study on PD (FINPARK). We included 2017 cases (diagnosed 1999-2015) with PD and 7934 controls without PD. Diabetes medication use was identified from Prescription Register (1995-2015) and categorized to insulins, biguanides, sulfonylureas, thiazolidinediones (TZDs), dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues and glinide. Exposure for each medication class was determined as none, at least 3 years before outcome and only within the three-year lag time before PD outcome. RESULTS: The use of insulins, biguanides, sulfonylureas, DPP-4 inhibitors, GLP-1 analogues or glinides was not associated with PD. Use of TZDs before lag time compared to non-use of TZDs (adjusted odds ratio (OR) 0.78; 95% Confidence interval (CI) 0.64-0.95) was associated with decreased risk of PD. CONCLUSIONS: Our nationwide case-control study of people with diabetes found no robust evidence on the association between specific diabetes medication classes and risk of PD. Consistent with earlier studies, TZD use was associated with slightly decreased risk of PD. The mechanism for this should be verified in further studies.

Disease-Modifying Antirheumatic Drugs and Risk of Parkinson Disease: Nested Case-Control Study of People With Rheumatoid Arthritis.

BACKGROUND AND OBJECTIVES: Epidemiologic studies have suggested a link between rheumatoid arthritis and Parkinson disease (PD). Disease-modifying antirheumatic drugs (DMARDs) might explain this association. The aim of this work was to evaluate the association between DMARDs and risk of PD in persons with rheumatoid arthritis. METHODS: This nested nationwide case-control study was conducted within the Finnish Parkinson's Disease (FINPARK) cohort, which includes 22,189 Finnish persons with clinically verified PD diagnosed in 1996 to 2015. The cases had recorded diagnosis of PD in the Special Reimbursement Register and had no exclusion diagnoses with symptoms that may be confused with PD within 2 years of PD diagnosis. This study included cases with PD diagnosed during 1999 to 2015 and rheumatoid arthritis diagnosed >3 years before PD. Rheumatoid arthritis was identified from the Finnish Care Register for Health Care and Special Reimbursement Register. Cases were matched with up to 7 controls by age, sex, duration of rheumatoid arthritis, and region. DMARDs were categorized into 5 classes, and data on purchased prescriptions were identified from the Prescription Register since 1995. Associations were studied with conditional logistic regression adjusted for confounders. RESULTS: Altogether, 315 cases with PD and 1,571 matched controls were included. The majority (>60%) were women, and the median duration of rheumatoid arthritis on matching date was 11.6 years for controls and 12.6 years for cases. Use of DMARDs was not associated with risk of PD with a 3-year lag period applied between exposure and outcome except chloroquine/hydroxychloroquine, which associated with decreased risk (adjusted odds ratio [OR] 0.74, 95% confidence interval [CI] 0.56-0.97). Other DMARDs, including sulfasalazine, methotrexate, gold preparations, and immunosuppressants, were not associated with PD. DISCUSSION: Our results suggest that the lower risk of PD in people with rheumatoid arthritis is not explained by DMARD use because these drugs in general did not modify the risk of PD among persons with rheumatoid arthritis. Association between chloroquine/hydroxychloroquine and lower risk of PD and the possible underlying mechanisms should be further investigated. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in individuals with rheumatoid arthritis using DMARDs, only chloroquine/hydroxychloroquine was associated with a potentially decreased risk of developing PD (adjusted OR 0.74, 95% CI 0.56-0.97).

Antipsychotic Use and Risk of Stroke Among Community-Dwelling People With Alzheimer's Disease.

OBJECTIVES: Antipsychotic use for neuropsychiatric symptoms in Alzheimer's disease (AD) is common despite the increased risk of cardiovascular events and mortality. There is limited and inconsistent evidence on the possible risk of stroke. We assessed whether antipsychotic initiation increases the risk of stroke in people with a verified diagnosis of AD and whether there is a difference in stroke risk between the 2 most commonly used antipsychotics, risperidone and quetiapine. DESIGN: Register-based exposure-matched cohort study. SETTING AND PARTICIPANTS: The Medication Use and Alzheimer's Disease (MEDALZ) cohort included 70,718 community-dwelling people with AD in Finland during 2005-2011. People with previous strokes were excluded. METHODS: For each incident antipsychotic user (n = 20,467), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with inverse probability of treatment-weighted (IPTW) Cox proportional hazards models. RESULTS: Compared with nonuse, antipsychotic use was associated with an increased risk of stroke within 60 days of antipsychotic initiation [IPTW hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.32-2.28]. However, there was no significant overall association between antipsychotic use and the risk of stroke (IPTW HR 1.09, 95% CI 0.98-1.22). There was no difference in stroke risk between risperidone and quetiapine (IPTW HR 1.12, 95% CI 0.91-1.37). CONCLUSIONS AND IMPLICATIONS: Stroke risk is increased shortly after antipsychotic initiation in people with AD, suggesting that even short-term use of antipsychotics should be avoided if possible. If antipsychotics are prescribed, effectiveness and safety should be assessed soon after initiation and treatment limited to the shortest possible duration.

Automated multi-dose dispensing in persons with and without Alzheimer's disease-impacts on pharmacotherapy.

PURPOSE: We investigated the drug use before and after transition to automated multi-dose dispensing (MDD) service among persons with Alzheimer's disease (AD) and compared whether the changes were similar in persons without AD. METHODS: The register-based Finnish nationwide MEDALZ cohort includes 70,718 community-dwelling persons diagnosed with AD during 2005-2011. Each person who initiated MDD was matched in both groups with a comparison person without MDD by age, gender and for persons with AD, also time since AD diagnosis at the start of MDD. The study cohort included 15,604 persons with AD in MDD and 15,604 no-MDD, and 5224 persons without AD in MDD and 5224 no-MDD. Point prevalence of drug use was assessed every 3 months, from 1 year before to 2 years after the start of MDD and compared between persons in MDD to those who did not have MDD. RESULTS: MDD was started on average 2.9 (SD 2.1) years after AD diagnosis. At the start of MDD, the prevalence of drug use increased especially for antipsychotics, antidepressants, opioids, paracetamol and use of ≥ 10 drugs among persons with and without AD. Prevalence of benzodiazepine use (from 12% 12 months before to 17% at start of MDD), memantine (from 29 to 46%) and ≥ 3 psychotropics (from 3.2 to 6.0%) increased among persons with AD. Decreasing trend was observed for benzodiazepine-related drugs, urinary antispasmodics and non-steroidal anti-inflammatory drugs. CONCLUSION: MDD seems to be initiated when use of psychotropics is initiated and the number of drugs increases.

Changes in the use of diabetes drugs among community-dwelling people with Alzheimer's disease.

BACKGROUND: Type 2 diabetes is common in persons with Alzheimer's disease (AD). Management of diabetes in persons with AD is challenging due to changing goals of care and susceptibility to adverse drug events including hypoglycemia. The aim of this study was to investigate the prevalence of diabetes drug use from 5 years before to 5 years after the time of AD diagnosis among persons with and without AD. METHODS: This was a nationwide register-based study of persons with and without AD and diabetes in Finland. We analyzed data from the Medication Use and Alzheimer's disease (MEDALZ) study that included 70,718 community-dwelling people diagnosed with AD from 2005 to 2011. The study population included 8418 persons with AD and 6666 matched persons without AD who were diagnosed with diabetes 5 years before AD diagnosis (index date). We defined the prevalence of diabetes drug use in three-month evaluation periods from 5 years before until 5 years after the index date. RESULTS: Nearly all people with diabetes (94% in both cohorts) used one or more diabetes drugs on the index date. The most prevalent drug metformin was used by 60.9% of people with AD and 59.1% of people without AD. The next most prevalent drugs were sulfonylureas and insulin. The prevalence of diabetes drug use was similar in people with and without AD but began to decline 1 year after AD diagnosis in the AD cohort compared to non-AD cohort. CONCLUSIONS: The decline in diabetes drug use after AD diagnosis may be attributed to clinicians and patients seeking to avoid serious adverse drug events including hypoglycemia. In addition, the findings may reflect personalized glycemic control and unintentional weight loss in persons with AD reducing the need for diabetes drugs.

Hip Fracture Risk in Antiepileptic Drug Initiators and Non-Initiators with Alzheimer's Disease.

OBJECTIVE: To determine the risk of hip fracture in persons with Alzheimer´s disease (AD) who initiated antiepileptic drugs (AEDs). METHODS: In the Medication use and AD (MEDALZ) cohort of 70,719 Finnish community dwellers with clinically verified incident AD diagnosis in 2005-2011, we identified all incident users of AEDs using national Prescription register. AEDs were classified as older (valproate, carbamazepine, clonazepam, phenytoin, levetiracetam, primidone) or newer (pregabalin, gabapentin, oxcarbazepine, lamotrigine, topiramate). We matched each user to 2 non-users. Incident hip fractures until 2015 were identified from the Care register for health care. We calculated inverse probability of treatment weighted hazard ratios (HR), with 95% confidence intervals, using Cox regression. RESULTS: Altogether 5522 incident users were identified and matched to 11,044 non-users (in both groups, women: 65%; median age: 81 years). Altogether 53.3% of users initiated with newer AEDs (pregabalin 79.8%, gabapentin 10.2%) while 46.7% initiated with older AEDs (valproate 67.6%, carbamazepine 13.0%). Age- and sex-adjusted IR of hip fracture per 100 person-years was 1.8 (95% CI 1.6-1.9) in non-users and 2.0 (95% CI 1.8-2.2) in users. Increased risk of hip fracture was observed in users (HR 1.17, 95% CI 1.05-1.30) compared with non-users. The risk was higher for short duration of use (<14 weeks, HR 3.64, 95% CI 2.90-4.58) than for medium duration (14 to <64 weeks, HR 1.74, 95% CI 1.48-2.05) or ≥64 weeks' use (HR 1.23, 95% CI 1.08-1.40), compared to non-users with same follow-up time. Older AEDs had HR of 1.46 (1.03-2.08) compared with newer AEDs. CONCLUSION: Our results imply that AED use is associated with an increased risk of hip fracture in people with AD. These findings prompt careful consideration before prescribing AEDs to persons with AD. Persons with AD treated with antiepileptics should be carefully monitored due to their increased risk of falling and fractures.

Association of recent hospitalisation with antidepressant initiation among community dwellers with Alzheimer's disease.

OBJECTIVES: Antidepressant are commonly prescribed to persons with cognitive disorders to treat depressive and other neuropsychiatric symptoms despite the inconclusive evidence on their effectiveness on this indication. We studied whether recent hospitalisation was associated with antidepressant initiation in people with Alzheimer's disease (AD). METHODS: The register-based Finnish nationwide Medication use and Alzheimer's disease cohort includes community-dwelling persons diagnosed with AD during 2005-2011 in Finland (n = 70,718). This study was restricted to people who initiated antidepressant use after AD diagnosis and had no active cancer treatment and schizophrenia or bipolar disorder diagnoses. We performed a nested case-control study with antidepressant initiators as cases. A matched noninitiator (sex, age and AD duration), was identified for each initiator (15,360 matched pairs). Recent hospitalisation was defined as hospital discharge within the past 14 days of initiation. RESULTS: Antidepressant initiators were four times more likely (adjusted odds ratio: 4.41, 95% confidence interval: 4.06-4.80) to have been hospitalised within the past 2 weeks before initiation (21.2%, n = 3250) than matched noninitiators (5.4%, n = 831) and the duration of hospital stay was significantly longer among initiators. Dementia was the most common main discharge diagnosis among both initiators (43.8%, n = 1423) and noninitiators (24.8%, n = 206). CONCLUSION: Recent hospitalisation was strongly associated with antidepressant initiation in persons with AD. Further studies are needed to investigate whether this is due to neuropsychiatric symptoms leading to hospital admission, inpatient care triggering or worsening neuropsychiatric symptoms or other indications. Nonpharmacological treatments for neuropsychiatric symptoms should be prioritised and the threshold for prescribing antidepressants should be high.

Coronary Revascularization and Postoperative Outcomes in People With and Without Alzheimer's Disease.

BACKGROUND: Little is known on the incidence and postoperative outcomes of revascularizations according to electivity in persons with Alzheimer's disease (AD). METHODS: The Medication Use and Alzheimer's disease (MEDALZ) cohort includes 70 718 community dwellers diagnosed with incident AD during 2005-2011 in Finland. For each person with AD, 1-4 age-, sex-, and hospital district-matched comparison persons without AD were identified. Altogether 448 persons with AD and 5909 without AD underwent revascularization during the follow-up. The outcomes were 30-day and 90-day re-admission rate after discharge, and all-cause 1-year and 3-year mortality. Risk of outcomes in persons with AD were compared to those without AD using Cox proportional hazard models adjusted with age, sex, comorbidities, statin use, revascularization type, length of stay, and support at discharge. RESULT: People with AD had less revascularizations (adjusted hazard ratio 0.24, 95% confidence interval 0.22-0.27). Emergency procedures were more common (42.6% vs 33.1%) than elective procedures (34.2% vs 48.6%) among people with AD. There was no difference in 30-day readmissions (0.97, 0.80-1.17) or 1-year mortality (1.04, 0.75-1.42) and 90 days readmission risk was lower in persons with AD (0.85, 0.74-0.98). People with AD had higher 3-year mortality (1.42, 1.15-1.74), but the risk increase was observed only for emergency (1.71, 1.27-2.31), not for elective procedures (0.96, 0.63-1.46). CONCLUSION: People with AD did not have worse readmission and mortality outcomes following elective revascularization. These findings in conjunction with lower revascularization rate especially for elective procedures raise questions on the threshold for elective procedures in people with AD.

Does Recent Hospitalization Increase Antipsychotic Initiation Among Community Dwellers With Alzheimer's Disease?

OBJECTIVES: Antipsychotics are often prescribed to persons with cognitive impairment in the hospital, but it is not known whether recent hospital care increases the risk of antipsychotic initiation in community dwellers with Alzheimer's disease (AD). We studied whether hospital care during the previous 2 weeks is associated with antipsychotic initiation in persons with AD. DESIGN: Register-based study. PARTICIPANTS AND SETTING: The nationwide Medication use and Alzheimer's disease (MEDALZ) cohort containing Finnish community dwellers with AD between 2005 and 2011 (N = 70,718) was used. METHODS: Incident antipsychotic use was identified with a 1-year washout period. Each new initiator was matched with noninitiator according to age, sex, and time since AD diagnosis (n = 22,281 matched pairs). The use of antipsychotics was identified from the Prescription Register. Information on hospital discharge within the past 2 weeks of antipsychotic initiation was extracted from the Hospital Discharge Register. RESULTS: Antipsychotic initiators were 5 times more likely to have recently been discharged from the hospital compared with the matched noninitiators (29.8% and 5.3%, respectively). In adjusted regression analyses, a hospital stay longer than a week and especially more than 2 months [odds ratio (OR) 4.40, 95% confidence interval (CI) 3.51-5.53], use of benzodiazepines and related drugs (OR 1.66, 95% CI 1.44-1.92), and memantine (OR 1.30, 95% CI 1.12-1.52) were associated with antipsychotic initiation. Older age (OR 0.77, 95% CI 0.62-0.95), asthma or chronic obstructive pulmonary disease (OR 0.73, 95% CI 0.60-0.89), diabetes (OR 0.82, 95% CI 0.69-0.97), and cardiovascular disease (OR 0.82, 95% CI 0.72-0.94) were associated with a lower risk of initiation. CONCLUSIONS AND IMPLICATIONS: Recent hospital care seems to be a risk factor for antipsychotic initiation in community-dwelling persons with AD. The need of antipsychotic treatment must be carefully assessed at the time of discharge. Well planned hospital discharge and home care might reduce antipsychotic initiation.

Increased Risk of Parkinson's Disease in Patients With Schizophrenia Spectrum Disorders.

BACKGROUND: PD comorbid with schizophrenia has been considered rare because these diseases associate with opposite alterations in the brain dopamine system. The objective of this study was to investigate the risk of PD after a diagnosis of a schizophrenia spectrum disorder. METHODS: Regionally, this was a retrospective record-based case-control study. The cohort included 3045 PD patients treated 2004-2019 in southwestern Finland. Nationally this was a nested case-control study using registers to examine Finnish patients who received a clinically confirmed PD diagnosis 1996-2015 (n = 22,189). PD patients with previously diagnosed schizophrenia spectrum disorder (separate analysis for schizophrenia) were included. Comparable non-PD control groups were derived from both data sets. All PD diagnoses were based on individual clinical examinations by certified neurologists. RESULTS: In PD patients, the prevalence of earlier schizophrenia spectrum disorder was 0.76% in regional data and 1.50% in nationwide data. In age-matched controls, the prevalence in the regional and national data was 0.16% and 1.31%, respectively. The odds ratio for PD after schizophrenia spectrum disorder diagnosis was 4.63 (95% CI, 1.76-12.19; P < 0.01) in the regional data and 1.17 (95% CI, 1.04-1.31; P < 0.01) in the national data. CONCLUSIONS: Schizophrenia spectrum disorder increases the risk of PD later in life. This association was observed in both individual patient data and nationwide register data. Therefore, despite the opposite dopaminergic disease mechanisms, schizophrenia spectrum disorder increases rather than decreases the risk of PD. The increased PD risk could be related to risk-altering effects of dopamine receptor antagonists or to the increased vulnerability of the dopamine system induced by illness phase-dependent dopamine dysregulation in schizophrenia/schizophrenia spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.