Association between Benzodiazepine Use and Dementia: Data Mining of Different Medical Databases

Takada, Mitsutaka; Fujimoto, Mai; Hosomi, Kouichi

doi:10.7150/ijms.16185

Cited by 50 publications

(39 citation statements)

References 35 publications

(47 reference statements)

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“…This association was independent of the risk factors associated with NPS groups (family history of dementia, personal history of psychiatric disorders). It is possible that this is an effect of treatment of NPS, which may have cognitive side effects [56–58]. It is also possible that it may reflect non-compliance with standard treatment.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors, Neuroanatomical Correlates, and Outcome of Neuropsychiatric Symptoms in Alzheimer’s Disease

Poulin

Bergeron

Dickerson

2017

JAD

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Background An integrative model of neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) is lacking. Objective In this study, we investigated the risk factors, anatomy, biology, and outcomes of NPS in AD. Methods 181 subjects were included from the Alzheimer’s Disease Neuroimaging Study (ADNI). NPS were assessed with the Neuropsychiatric Inventory Questionnaire at baseline and 6 months. NPI >3 was used as a threshold for NPS positivity. Three NPS courses were characterized: 1) minimal/absent (negative at 0 and 6 months, n = 77); 2) fluctuating (positive only at one time point, n = 53); 3) persistent (positive at both time points, n = 51). We examined the association between NPS course and family history of dementia, personal history of psychiatric disorders, cerebrospinal fluid biomarkers, atrophy patterns, as well as longitudinal cognitive and functional measures at 12 and 24 months (MMSE, CDR-SOB, FAQ). Results AD subjects with absent, fluctuating, or persistent NPS had similar CSF amyloid-β and tau levels. AD subjects with minimal/absent NPS had less personal history of psychiatric disorders (35%) than those with fluctuating (57%; p = 0.015) or persistent NPS (47%, not significant). At 24 months, AD subjects with persistent NPS had worse cognitive (MMSE; p = 0.05) and functional (CDR-SOB; p = 0.016) outcomes. Dorsolateral prefrontal atrophy was seen in persistent NPS, but not in fluctuating NPS. Conclusions Our results suggest that individuals with personal history of psychiatric disorders might be more vulnerable to develop NPS throughout the course of AD. The worst cognitive and functional outcomes associated with NPS in AD underscores the importance of monitoring NPS early in the disease course.

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Section: Discussionmentioning

confidence: 99%

Risk Factors, Neuroanatomical Correlates, and Outcome of Neuropsychiatric Symptoms in Alzheimer’s Disease

Poulin

Bergeron

Dickerson

2017

JAD

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“…Retrospective data analysis was performed using two different RWD in Japan. The Japanese Adverse Drug Event Report (JADER), a public spontaneous ADR database constructed by the Pharmaceuticals and Medical Devices Agency (PMDA), and a large prescription database constructed by a database vendor (Japan Medical Information Research Institute, Inc Japan [JMIRI]) database were analysed.…”

Section: Methodsmentioning

confidence: 99%

Polypharmacy in elderly patients in Japan: Analysis of Japanese real‐world databases

et al. 2020

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What is known and objective Polypharmacy is associated with an increased risk of adverse drug reactions (ADRs) and drug interactions, decreased adherence to medication and increased medical cost. Recently, polypharmacy has become a major problem in medical care in Japan as a result of the increase in the ageing population. The purpose of this study was to investigate the current situation of polypharmacy and the association between polypharmacy and adverse events. Methods A retrospective data analysis was performed using two different real‐world data from 2007 to 2015 in Japan. The Japanese Adverse Drug Event Report (JADER), a public spontaneous adverse drug reaction database constructed by the Pharmaceuticals and Medical Devices Agency (PMDA), and a large prescription database constructed by a database vendor (Japan Medical Information Research Institute, Inc Japan [JMIRI]) were analysed. Trends of polypharmacy during the study period were investigated. Results and discussion The mean number of drugs per report in the JADER database and per prescription in the JMIRI databases during the study period ranged from 4.8 to 5.6 and 3.5 to 3.7, respectively. The mean number of drugs increased with age in both the JADER and JMIRI databases, and the peak of the mean number of drugs was at 80‐89 years (5.74 drugs) in the JADER database and at 90‐99 years (4.97 drugs) in the JMIRI database. What is new and conclusions The number of drugs increased until age 90 years or more, even though adverse events are more likely to occur after the age of 80 in Japan. Therefore, polypharmacy in the elderly should be focused on the patients aged ≥80 years rather than patients aged ≥65 years from the viewpoint of the prevention of adverse events.

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“…All other studies focused on the association between BZD and dementia risk. Eight case control studies (Billioti de Gage et al, ; Chan et al, ; Gomm et al, ; Imfeld, Bodmer, Jick, & Meier, ; Takada, Fujimoto, & Hosomi, ; Tapiainen et al, ; C.‐S. Wu, Ting, Wang, Chang, & Lin, ; C.‐S.…”

Section: Resultsmentioning

confidence: 99%

“…All other studies focused on the association between BZD and dementia risk. Eight case control studies (Billioti de Gage et al, 2014;Chan et al, 2017;Imfeld, Bodmer, Jick, & Meier, 2015;Takada, Fujimoto, & Hosomi, 2016;Tapiainen et al, 2018;C.-S. Wu, Ting, Wang, Chang, & Lin, 2011;C.-S. Wu, Wang, Chang, & Lin, 2009) and four cohort studies (Billioti de Gage et al, 2012;Gallacher et al, 2012;Gray et al, 2016;Shash et al, 2016) showed a significant association between chronic BZD use and increased risk of dementia.…”

Section: Benzodiazepinesmentioning

confidence: 99%

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

Barus

Béné

Deguil

et al. 2019

British J Pharmacology

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Many risk factors are known to induce or precipitate dementia. Drugs acting via different mechanisms can modulate cognitive performance and exert either beneficial or deleterious effects on cognition through functional or neuropathological mechanisms. This review discusses the association between several classes of drugs and cognitive impairment and dementia risk. These drugs can be divided into drugs targeting CNS disorders (e.g., anticholinergic drugs, antiepileptics, antipsychotics, benzodiazepines, and opioids) and drugs targeting non‐CNS disorders (e.g., antidiabetics, antihypertensives, proton pump inhibitors, and statins). Furthermore, we sought to highlight the pharmacological mechanisms underlying their possible detrimental or beneficial effects on cognition. Anticholinergic and antiepileptic drugs were excluded from this review because their effects on cognition are well known. Studies investigating benzodiazepines have revealed an increased risk of dementia. Conclusions on dementia risk or cognitive impairment regarding opioids and antipsychotic drugs are difficult to draw. These different classes appear to impair cognition not by a single clear mechanism of action specific to each class but by several relatively interdependent and interconnected mechanisms (e.g., impaired neurotransmission, neuroinflammation, neuronal death, oxidative stress, or interactions with dementia‐related pathways). The dementia risk initially associated with the use of proton pump inhibitors might have been overestimated. In contrast, statins, antihypertensive medications, and antidiabetics could potentially decrease the risk of dementia and cognitive impairment by acting in ways opposite to the mechanisms cited above. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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Association between Benzodiazepine Use and Dementia: Data Mining of Different Medical Databases

Cited by 50 publications

References 35 publications

Risk Factors, Neuroanatomical Correlates, and Outcome of Neuropsychiatric Symptoms in Alzheimer’s Disease

Risk Factors, Neuroanatomical Correlates, and Outcome of Neuropsychiatric Symptoms in Alzheimer’s Disease

Polypharmacy in elderly patients in Japan: Analysis of Japanese real‐world databases

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

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