Dataset Information

Alzheimer's disease and related dementias risk: Comparing users of non-selective and M3-selective bladder antimuscarinic drugs.

ABSTRACT:

Purpose

Bladder antimuscarinic (BAM) drug use is associated with increased risk of Alzheimer's disease and related dementias (ADRD). It is hypothesized that BAMs with non-selective receptor binding may increase ADRD risk more than M3-selective BAMs. This study compared ADRD risk for users of non-selective and M3-selective BAMs and examines ADRD risk associated with overall BAM use.

Methods

Retrospective cohort study of Medicare claims for 71?688 individuals who used BAM drugs during 2007-2009 without an ADRD diagnosis. We compared ADRD incidence (2011-2016) between non-selective BAM users (fesoterodine, flavoxate, oxybutynin, tolterodine, trospium) and M3-selective BAM users (darifenacin, solifenacin). Logistic regressions compared individuals using target drugs in the same category of total standardized daily doses (TSDD) as a standardized measure of drug exposure, and adjusted for age, sex, race/ethnicity, healthcare utilization, other medication use, socioeconomic status, and comorbidities. Secondary analyses compared ADRD risk associated with different doses of BAMs overall.

Results

Non-selective BAM use (compared to M3-selective) was not significantly associated with ADRD incidence. Odds ratios for non-selective use were 0.97 (CI: 0.89-1.04) for 1-364 TSDD, 0.94 (CI: 0.83-1.06) for 365-729, 1.00 (CI: 0.87-1.16) for 730-1094, and 1.03 (CI: 0.88-1.20) for >1094. Higher TSDD of BAMs overall (combining both non-selective and M3-selective BAMs), when compared to 1-364 TSDD, were associated with increased ADRD incidence (OR = 1.05 (CI: 0.99-1.10) for 365-729, OR = 1.11 (CI: 1.05-1.17) for 730-1094, and OR = 1.10 (CI: 1.04-1.15) for >1094).

Conclusions

Non-selective and M3-selective BAM users had similar odds of ADRD incidence, and BAM use overall was significantly associated with ADRD incidence.

SUBMITTER: Barthold D

PROVIDER: S-EPMC7825274 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alzheimer's disease and related dementias risk: Comparing users of non-selective and M3-selective bladder antimuscarinic drugs.

Barthold Douglas D Marcum Zachary A ZA Gray Shelly L SL Zissimopoulos Julie J

Pharmacoepidemiology and drug safety 20200827 12

<h4>Purpose</h4>Bladder antimuscarinic (BAM) drug use is associated with increased risk of Alzheimer's disease and related dementias (ADRD). It is hypothesized that BAMs with non-selective receptor binding may increase ADRD risk more than M3-selective BAMs. This study compared ADRD risk for users of non-selective and M3-selective BAMs and examines ADRD risk associated with overall BAM use.<h4>Methods</h4>Retrospective cohort study of Medicare claims for 71 688 individuals who used BAM drugs duri ...[more]

PMID: 32852147

Similar Datasets

Project description:BackgroundThe Medicare Advantage (MA) program is rapidly growing. Limited evidence exists about the care experiences of MA beneficiaries with Alzheimer's Disease and Related Dementia (ADRD). Our objective was to compare care experiences for MA beneficiaries with and without ADRD.MethodsWe examined MA beneficiaries who completed the Medicare Advantage Consumer Assessment of Healthcare Providers and Systems (CAHPS) and used inpatient, nursing home, or home health services in the past 3 years. We classified beneficiaries with ADRD using the presence of diagnosis codes in hospitals, nursing homes, and home health records. Our key measures included overall ratings of care and health plan, and indices of receiving timely care, care coordination, receiving needed care, and customer service. We compared differences between beneficiaries with and without ADRD using regression analysis adjusting for demographic, health, and plan characteristics, and stratifying by proxy response status.ResultsAmong beneficiaries sampled by CAHPS, 22.2% with ADRD completed the survey compared to 38.5% without ADRD. Among proxy responses, beneficiaries with ADRD were 4.2 (95% CI: 0.1-8.4) percentage points less likely to report a high score for receiving needed care, and 3.5 percentage points (95% CI: 0.2-6.9) less likely to report a high score for customer service. Among non-proxy responses, those with ADRD were 9.0 (95% CI: 5.5-12.5) percentage points less likely to report a high score for needed care, and 8.5 (95% CI: 5.4-11.5) percentage points less likely to report a high score for customer service.ConclusionsADRD respondents to the CAHPS were more likely to be excluded from CAHPS performance measures because they did not meet eligibility requirements and rates of non-response were higher. Among responders with or without a proxy, MA enrollees with an ADRD diagnosis reported worse care experiences in receiving needed care and in customer service than those without an ADRD diagnosis.

Project description:Currently, more than 55 million people around the world suffer from dementia, and Alzheimer's disease-related dementia (ADRD) accounts for nearly 60-70% of all those cases. The spread of AD pathology and progressive neurodegeneration in the hippocampus and cerebral cortex is strongly correlated with cognitive decline in AD patients; however, the molecular underpinning of the ADRD causality is still unclear. Studies of postmortem AD brains and animal models of AD suggest that elevated endoplasmic reticulum (ER) stress may have a role in ADRD pathology through altered neurocellular homeostasis in brain regions associated with learning and memory. To study the ER stress-associated neurocellular response and its effects on neurocellular homeostasis and neurogenesis, we modeled an ER stress challenge using Thapsigargin (TG), a specific inhibitor of sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), in induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) of two individuals from our Mexican American Family Study (MAFS). High-content screening and transcriptomic analysis of the control and ER stress-challenged NSCs showed that NSC’s ER stress response resulted in a significant decline in NSC self-renewal and an increase in apoptosis and cellular oxidative stress. A total of 2300 genes were significantly (moderated t statistics FDR corrected p-value ≤ 0.05 and Fold Change absolute ≥ 2.0) differentially expressed (DE). Pathway enrichment and gene network analysis of DE genes suggests that all three unfolded protein response (UPR) pathways (PERK, IRE1, and ATF6) were significantly activated and cooperatively regulated the NSC’s transcriptional response to ER stress. Our results show that IRE1/XBP1 mediated transcriptional regulation of E2F1 and its downstream targets have a dominant role in inducing G1/S-phase cell cycle arrest in the ER stress-challenged NSCs. The ER stress-challenged NSCs also showed activation of CHOP-mediated apoptosis and dysregulation of synaptic plasticity and neurotransmitter homeostasis-associated genes. Overall, our results suggest that ER stress-associated attenuation of NSC self-renewal, increased apoptosis, and dysregulated synaptic plasticity and neurotransmitter homeostasis plausibly play a role in the causation of ADRD.

Dataset Information

Alzheimer's disease and related dementias risk: Comparing users of non-selective and M3-selective bladder antimuscarinic drugs.

Purpose

Methods

Results

Conclusions

Publications

Alzheimer's disease and related dementias risk: Comparing users of non-selective and M3-selective bladder antimuscarinic drugs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets