Proton pump inhibitors and the risk of Alzheimer’s disease and non-Alzheimer’s dementias

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Abstract

Proton pump inhibitors (PPIs) are among the most prescribed medications. Previous epidemiological studies have presented contradictory results about PPIs and the risk of dementia. Our objective was to investigate the association between the use of PPIs and an increasing risk of incident AD or non-AD dementias. A community-based retrospective cohort study was conducted based on the data available from 1st January 2002 to 31st December 2015 in the Catalan health service (CatSalut) system. This cohort included all PPI users (N = 36,360) and non-users (N = 99,362). A lag window of 5 years was considered between the beginning of the PPI treatment and the diagnosis of dementia. PPI use was not associated with the risk of AD (adjusted odds ratio (OR) 1.06) (95% CI 0.93–1.21; p = 0.408). A weakly but significantly increased risk of non-AD dementias was observed among PPI users (adjusted OR 1.20, 95% CI 1.05–1.37; p = 0.007). A higher dose of PPIs was not associated with an increased risk of either AD or non-AD dementias (OR 1.20; 95% CI 0.91–1.61 and OR 0.95; 95% CI 0.74–1.22, respectively). Regarding the number of PPIs used, we observed an increased risk of AD (OR 1.47; 95% CI 1.18–1.83) and non-AD dementias (OR 1.38; 95% CI 1.12–1.70) in users of two types of PPIs compared with those who used only one type. We did not find a higher incidence of AD among PPI users, but a weak increase in the risk of non-AD dementias among PPI users was observed.

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The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Guy M McKhann, David S. Knopman, Howard Chertkow … (2011)

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. Copyright © 2011. Published by Elsevier Inc.

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Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia.

Katya Rascovsky, John R. Hodges, David Knopman … (2011)

Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.

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Diagnosis and management of dementia with Lewy bodies

Ian G. McKeith, Bradley F. Boeve, Dennis W. Dickson … (2017)

The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.

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Author and article information

Contributors

Gerard Piñol-Ripoll: gerard_437302@hotmail.com

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 3 December 2020

Publication date PMC-release: 3 December 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 21046

Affiliations

[1 ]GRID grid.420395.9, ISNI 0000 0004 0425 020X, Unitat Trastorns Cognitius (Cognitive Disorders Unit), Clinical Neuroscience Research Group, Santa Maria University Hospital, , IRBLleida, ; Rovira Roure no. 44, 25198 Lleida, Spain

[2 ]Pharmacy Department, Servei Català de La Salut (Catalan Health Services), Lleida, Spain

[3 ]GRID grid.22061.37, ISNI 0000 0000 9127 6969, Unitat D’Avaluació Clínica (Clinical Evaluation Unit), , Institut Català de La Salut (Catalan Institute of Health), ; Lleida, Spain

[4 ]Accenture Innovation Center, Barcelona, Spain

[5 ]GRID grid.454240.3, Barcelona Graduate School of Economics (BGSE), ; Barcelona, Spain

[6 ]GRID grid.36083.3e, ISNI 0000 0001 2171 6620, Universitat Oberta de Catalunya (UOC), ; Barcelona, Spain

[7 ]GRID grid.420395.9, ISNI 0000 0004 0425 020X, Group of Translational Research in Respiratory Medicine, Arnau de Vilanova University Hospital and Santa Maria University Hospital, , IRBLleida, ; Lleida, Spain

[8 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Biomedical Research Networking Center in Respiratory Diseases (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, CIBERES), ; Madrid, Spain

Article

Publisher ID: 78199

DOI: 10.1038/s41598-020-78199-0

PMC ID: 7713356

PubMed ID: 33273636

SO-VID: 6a7a3fdd-2235-42af-8b2d-c483bb9f0692

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 9 April 2020

Date accepted : 23 November 2020

Funding

Funded by: Department of Health PERIS 2019

Award ID: SLT008/18/00050

Award Recipient : Francisco Torres-Bondia

Funded by: Department of Health PERIS 2016

Award ID: SLT002/16/00364

Award Recipient : Leonardo Galván

Funded by: FundRef https://doi.org/10.13039/501100004587, Instituto de Salud Carlos III;

Award ID: CP19/00108

Award Recipient : Leonardo Galván

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ScienceOpen disciplines: Uncategorized

Keywords: cognitive ageing,dementia

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ScienceOpen disciplines: Uncategorized

Keywords: cognitive ageing, dementia

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Proton pump inhibitors and the risk of Alzheimer’s disease and non-Alzheimer’s dementias

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Karger: Neurology and Neuroscience

Most cited references 39

The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia.

Diagnosis and management of dementia with Lewy bodies

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Cited by 12

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