The Risk of Head Injuries Associated With Antipsychotic Use Among Persons With Alzheimer's disease

Tapiainen, V.; Lavikainen, Piia; Koponen, Marjaana; Taipale, Heidi; Tanskanen, Antti; Tiihonen, Jari; Hartikainen, Sirpa; Tolppanen, Anna‐Maija

doi:10.1111/jgs.16275

Cited by 17 publications

(16 citation statements)

References 33 publications

(66 reference statements)

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“…During recent decades, the sequential events that occur in the development and pathology of AD have been extensively studied, yet the precise etiology of the disease remains elusive, and current preventative and curative strategies are largely unsuccessful (Rong et al, 2017;Rasmussen and Langerman, 2019). Considering the complexity of AD pathology, it is apparent that other risk factors also exist besides those known, such as gender, education, smoking, dietary habit, depression, hypertension, diabetes mellitus, obesity, and head injury (Shinohara et al, 2014;Dursun et al, 2016;Badea et al, 2019;Jackson et al, 2019;Tapiainen et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Chronic Periodontitis and Alzheimer Disease: A Putative Link of Serum Proteins Identification by 2D-DIGE Proteomics

Rong

Xiang

et al. 2020

Front. Aging Neurosci.

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Increasing evidence indicates Chronic Periodontitis (CP) is a comorbidity of Alzheimer's disease (AD), which is the most common form of age-related dementia, and for the latter, effective diagnostic and treatment strategies are lacking. Although inflammation is present in both diseases, the exact mechanisms and cross-links between CP and AD are poorly understood; and a direct association between the two has not been reported. This study aimed to identify a direct serum proteins link between AD and CP. Two-dimensional differential in-gel electrophoresis was employed to analyze serum samples from 12 CP patients and 12 age-matched controls. Furthermore, to determine the molecular link between CP and AD, neuroblastoma SK-N-SH APPwt cells were treated with 1 µg/ml of lipopolysaccharide from Porphyromonas gingivalis (P.g-LPS). Ten differentially expressed proteins were identified in CP patients. Among them, nine proteins were up-regulated, and one protein was down-regulated. Of the 10 differentially expressed proteins, five proteins were reportedly involved in the pathology of AD: Cofilin-2, Cathepsin B, Clusterin, Triosephosphate isomerase, and inter-alpha-trypsin inhibitor heavy chain H4 (ITI-H4). Western blotting indicated significantly higher expression of Cofilin-2, Cathepsin B, and Clusterin and lower expression of ITI-H4 in the CP group than in the Control group. The serum concentration of Cathepsin B has a good correlation with MMSE scores. Moreover, the protein level of Cathepsin B (but not that of ADAM10 and BACE1) increased significantly along with a prominent increase in Aβ 1-40 and Aβ 1-42 in the cell lysates of P.g-LPS-treated SK-N-SH APPwt cells. Cathepsin B inhibition resulted in a sharp decrease in Aβ 1-40 and Aβ 1-42 in the cell lysates. Furthermore, TNF-α was one of the most important inflammatory cytokines for the P.g-LPS-induced Cathepsin B upregulation in SK-N-SH APPwt cells. These results show that CP and AD share an association, while Cathepsin B could be a key link between the two diseases. The discovery of the identical serum proteins provides a potential mechanism underlying the increased risk of AD in CP patients, which could be critical for elucidating the pathophysiology of AD.

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Section: Introductionmentioning

confidence: 99%

Chronic Periodontitis and Alzheimer Disease: A Putative Link of Serum Proteins Identification by 2D-DIGE Proteomics

Rong

Xiang

et al. 2020

Front. Aging Neurosci.

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“…This wide-spread use of quetiapine might be problematic as safety is not thoroughly evaluated with the use of quetiapine in low dose. However, prior observational studies have indicated increased risk of metabolic disturbances (Carr et al ., 2016), fall-related injuries (Tapiainen et al ., 2020), stroke (Correll et al ., 2015) and all-cause mortality (Gerhard et al ., 2020; Reutfors et al ., 2020) with the use of quetiapine in individuals without severe mental disorders.…”

Section: Discussionmentioning

confidence: 99%

Use of antipsychotics in Denmark 1997–2018: a nation-wide drug utilisation study with focus on off-label use and associated diagnoses

Andersen

Correll

et al. 2021

Epidemiol Psychiatr Sci

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Aims Antipsychotics are primarily labelled for the treatment of severe mental illness and have documented clinical utility in certain neurological disorders or palliative care. However, off-label use of antipsychotics is common and increasing, and prior studies on antipsychotic utilisation have not specifically assessed users in neurology, palliative care or general practice. We aimed to explore diagnoses associated with antipsychotic use, treatment patterns and characteristics of users without diagnoses relevant to antipsychotic treatment. Methods Population-based study identifiying all users of antipsychotics in Denmark (pop 5.7 mio.) 1997–2018 in the Danish National Prescription Register (DNPR). Possible indications for antipsychotic therapy were evaluated using in- and outpatient contacts from the DNPR. Users were divided hierarchically into six groups: severe mental disorders (schizophrenia, bipolar-spectrum disorders), chronic mental disorders (dementias, mental retardation, autism), other mental disorders (depression-spectrum, anxiety and personality disorders, etc.), selected neurological diseases, cancer and antipsychotic users without any of these diagnoses. This last group was characterised regarding demographics, antipsychotic use, health care utilisation and likely antipsychotic treatment initiator in 2018. Results Altogether, 630 307 antipsychotic users were identified, of whom 127 649 had filled prescriptions during 2018. Users without diagnoses relevant to antipsychotic treatment comprised of the largest group (37%), followed by schizophrenia and bipolar-spectrum disorders (34%), other mental disorders (15%), dementia, autism and mental retardation (11%), cancer (2.2%) and neurological diagnoses (2.0%). Of 37 478 incident users in 2018, 39% had no diagnosis relevant to antipsychotic treatment, 7.9% had major depression, 7.7% neurotic/stress-related disorders and 7.5% dementia. Quetiapine was most commonly used, both overall (51%) and among users without diagnoses relevant to antipsychotic treatment (58%). Of 14 474 incident users in 2018 without diagnoses relevant to antipsychotic treatment, treatment was most likely initiated by a general practitioner (65%), with only 17% seeing a psychiatrist during the following year. As many as 18% of patients with adjustment disorders and 14% of those without relevant diagnoses for antipsychotic use, remained on antipsychotic treatment 5 years after their first prescription. Conclusions Over one-third of antipsychotic users in Denmark did not have psychiatric, neurological or cancer diagnoses as possible indications for antipsychotic therapy. Many antipsychotics are initiated or prescribed in general practice, and a concerningly large subgroup without documented diagnoses relevant for antipsychotics continued to receive them. Rational prescribing, adequate side effect monitoring and further research into reasons for the observed antipsychotic use patterns and their risk–benefit ratio are needed.

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“…The Kuopio Research Centre of Geriatric Care focuses on pharmacoepidemiology in people with Alzheimer's disease and Parkinson's disease. This includes aetiological research, drug utilization studies and outcome studies [40,41]. Primary sources of data are the nationwide MEDication use and ALZheimer's disease (MEDALZ) study [42] on people with Alzheimer's disease, and the Finnish Medication and Parkinson's disease (FINPARK) study on people with Parkinson's disease [43].…”

Section: University Of Eastern Finland Finlandmentioning

confidence: 99%

Application of Healthcare ‘Big Data’ in CNS Drug Research: The Example of the Neurological and mental health Global Epidemiology Network (NeuroGEN)

et al. 2020

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Neurological and psychiatric (mental health) disorders have a large impact on health burden globally. Cognitive disorders (including dementia) and stroke are leading causes of disability. Mental health disorders, including depression, contribute up to one-third of total years lived with disability. The Neurological and mental health Global Epidemiology Network (NeuroGEN) is an international multi-database network that harnesses administrative and electronic medical records from Australia, Asia, Europe and North America. Using these databases NeuroGEN will investigate medication use and health outcomes in neurological and mental health disorders. A key objective of NeuroGEN is to facilitate high-quality observational studies to address evidence-practice gaps where randomized controlled trials do not provide sufficient information on medication benefits and risks that is specific to vulnerable population groups. International multi-database research facilitates comparisons across geographical areas and jurisdictions, increases statistical power to investigate small subpopulations or rare outcomes, permits early post-approval assessment of safety and effectiveness, and increases generalisability of results. Through bringing together international researchers in pharmacoepidemiology, NeuroGEN has the potential to be paradigmchanging for observational research to inform evidence-based prescribing. The first focus of NeuroGEN will be to address evidence-gaps in the treatment of chronic comorbidities in people with dementia.

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The Risk of Head Injuries Associated With Antipsychotic Use Among Persons With Alzheimer's disease

Cited by 17 publications

References 33 publications

Chronic Periodontitis and Alzheimer Disease: A Putative Link of Serum Proteins Identification by 2D-DIGE Proteomics

Chronic Periodontitis and Alzheimer Disease: A Putative Link of Serum Proteins Identification by 2D-DIGE Proteomics

Use of antipsychotics in Denmark 1997–2018: a nation-wide drug utilisation study with focus on off-label use and associated diagnoses

Application of Healthcare ‘Big Data’ in CNS Drug Research: The Example of the Neurological and mental health Global Epidemiology Network (NeuroGEN)

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