Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study

Gray, Shelly L.; Dublin, Sascha; Yu, Onchee; Walker, Rod; Anderson, Melissa L.; Hubbard, Rebecca A.; Crane, Paul K.; Larson, Eric B.

doi:10.1136/bmj.i90

Cited by 169 publications

(152 citation statements)

References 34 publications

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“…Participants who withdrew from ACT or died before the end of the study period and before any outcome onset were censored at their last study visit. Timing of AD or dementia onset was set as the midpoint between the ACT visit that triggered the diagnosis and the preceding visit, as is ACT's convention . For the analyses of AD, onset of non‐AD dementia was treated as a censoring event.…”

Section: Methodsmentioning

confidence: 99%

Serum Cholesterol and Incident Alzheimer's Disease: Findings from the Adult Changes in Thought Study

Marcum

Walker

Bobb

et al. 2018

J American Geriatrics Society

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Background: Serum total cholesterol (TC) levels may be associated with Alzheimer’s disease (AD) risk. Objective: To evaluate associations between HDL and non-HDL cholesterol levels at specific ages and subsequent AD risk. Design, Setting, and Participants: Prospective population-based cohort study using data from Adult Changes in Thought (ACT). Participants were 65 years or older with no dementia at ACT study entry. We identified separate, partially overlapping, sub-cohorts of ACT participants who were eligible for each age band-specific analysis (50–59, 60–69, 70–79, and 80–89 years old; n=1088, n=2852, n=2344, n=537, respectively). Measurements: Exposure consisted of clinical measures of TC and HDL from laboratory data during a given age band. Outcomes of incident AD assessed post-age band using standard research diagnostic criteria. Statistical analyses used adjusted Cox proportional hazards regression models for each exposure and outcome pair within an age band. Cholesterol exposures modeled using cubic splines. Results: For non-HDL, we found a statistically significant association with AD risk in the 60–69 (omnibus p=0.005) and 70–79 (omnibus p=0.04) age bands, suggesting a potential U-shaped relationship (increased risk at low and high levels). For example, people age 60–69, compared with a person with an average non-HDL level of 160 mg/dL, a person with an average non-HDL level of 120 mg/DL had a 29% increased AD hazard (HR 1.29, 95% CI 1.04–1.61), while a person with an average non-HDL level of 210 mg/dL had a 16% increased hazard (HR 1.16, 95% CI 1.01–1.33). We did not find a statistically significant association for HDL cholesterol and AD risk. Conclusion: People with low (120 mg/dL) and high (210 mg/dL) levels of non-HDL cholesterol during their 60s and 70s had modestly higher risk for AD compared to people with intermediate (160 mg/dL) levels of non-HDL cholesterol. The extreme age bands (50s and 80s) were limited in sample size.

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Section: Methodsmentioning

confidence: 99%

Serum Cholesterol and Incident Alzheimer's Disease: Findings from the Adult Changes in Thought Study

Marcum

Walker

Bobb

et al. 2018

J American Geriatrics Society

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“…Six studies were case-control design studies [17][18][19][20][21][22] and 4 were cohort studies [23][24][25][26] . The included studies were published between 1983 and 2013, thus spanning 31 years.…”

Section: Systematic Reviewmentioning

confidence: 99%

“…The included studies were published between 1983 and 2013, thus spanning 31 years. Five studies were conducted in Europe [18,19,[24][25][26] , 3 in Asia [17,21,22], and the remaining 2 in North America [20,23] . Eight studies reported that the age at the onset of dementia was over 65 years but 2 studies reported an age of onset below 60 years [24,25] .…”

Section: Systematic Reviewmentioning

confidence: 99%

Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis

et al. 2016

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Background: Benzodiazepines are a widely used medication in developed countries, particularly among elderly patients. However, benzodiazepines are known to affect memory and cognition and might thus enhance the risk of dementia. The objective of this review is to synthesize evidence from observational studies that evaluated the association between benzodiazepines use and dementia risk. Summary: We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risk of benzodiazepines use on dementia outcome. All control observational studies that compared dementia outcome in patients with benzodiazepine use with a control group were included. We calculated pooled ORs using a random-effects model. Ten studies (of 3,696 studies identified) were included in the systematic review, of which 8 studies were included in random-effects meta-analysis and sensitivity analyses. Odds of dementia were 78% higher in those who used benzodiazepines compared with those who did not use benzodiazepines (OR 1.78; 95% CI 1.33-2.38). In subgroup analysis, the higher association was still found in the studies from Asia (OR 2.40; 95% CI 1.66-3.47) whereas a moderate association was observed in the studies from North America and Europe (OR 1.49; 95% CI 1.34-1.65 and OR 1.43; 95% CI 1.16-1.75). Also, diabetics, hypertension, cardiac disease, and statin drugs were associated with increased risk of dementia but negative association was observed in the case of body mass index. There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the sensitivity analyses. There was significant statistical and clinical heterogeneity among the studies for the main analysis and most of the sensitivity analyses. Key Messages: Our results suggest that benzodiazepine use is significantly associated with dementia risk. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or the result of some unmeasured confounding variable. Therefore, more research is needed.

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“…14 All of these medications adversely impact cognition, 13,15–17 while benzodiazepines are possibly associated with incident dementia, 18 though evidence is mixed. 19 These potential harms for older adults are particularly concerning given growing evidence that much psychotropic prescribing occurs in the absence of significant symptoms 20 or a clearly-defined mental disorder. 21,22 …”

Section: Introductionmentioning

confidence: 99%

National Trends in Antidepressant, Benzodiazepine, and Other Sedative-Hypnotic Treatment of Older Adults in Psychiatric and Primary Care

Maust¹,

Blow²,

Wiechers³

et al. 2017

J. Clin. Psychiatry

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Objective To describe how use of antidepressants, benzodiazepines, and other anxiolytic/sedative-hypnotics among older adults (age ≥65) has changed over time among visits to primary care providers and psychiatrists in the United States. Method Data came from the National Ambulatory Medical Care Survey (years 2003–2005 and 2010–2012), a nationally-representative cross-section of outpatient physician visits. Analysis focused on visits to primary care providers (n=14,282) and psychiatrists (n=1,095) at which an antidepressant, benzodiazepine, or other anxiolytic/sedative-hypnotic was prescribed, which were stratified by demographic and clinical characteristic (including ICD-9-CM diagnosis) and compared across study intervals. Odds of medication use were calculated for each stratum, adjusting for demographic and clinical characteristics. Results The visit rate by older adults to primary care providers where any of the medications were prescribed rose from 16.4% to 21.8% (AOR 1.43, p<0.001), while remaining steady among psychiatrists (75.4% v. 68.5%; AOR 0.69, p=0.11). Primary care visits rose for antidepressants (9.9% to 12.3%; AOR 1.28, p=0.01) and other anxiolytic/sedative-hypnotics (3.4% to 4.7%; AOR 1.39, p=0.01), but the largest growth was among benzodiazepines (5.6% to 8.7%; AOR 1.62, p<0.001). Among patients in primary care, increases primarily occurred among men, non-Hispanic white patients, and both those with pain diagnoses as well as those without any mental health or pain diagnoses. Conclusion From 2003–2012, use of the most common psychotropic medications among older adults seen in primary care increased, concentrated among patients with no mental health or pain diagnosis. As the population of older adults grows and receives mental health treatment in primary care, it is critical to examine the appropriateness of psychotropic use.

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Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study

Cited by 169 publications

References 34 publications

Serum Cholesterol and Incident Alzheimer's Disease: Findings from the Adult Changes in Thought Study

Serum Cholesterol and Incident Alzheimer's Disease: Findings from the Adult Changes in Thought Study

Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis

National Trends in Antidepressant, Benzodiazepine, and Other Sedative-Hypnotic Treatment of Older Adults in Psychiatric and Primary Care

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