Cumulative Anticholinergic Burden and its Predictors among Older Adults with Alzheimer's Disease Initiating Cholinesterase Inhibitors.
Cumulative anticholinergic burden refers to the cumulative effect of multiple medications with anticholinergic properties. However, concomitant use of cholinesterase inhibitors (ChEIs) and anticholinergic burden can nullify the benefit of the treatment and worsen Alzheimer's disease (AD). A literature gap exists regarding the extent of the cumulative anticholinergic burden and associated risk factors in AD. Therefore, this study evaluated the prevalence and predictors of cumulative anticholinergic burden among patients with AD initiating ChEIs.
A retrospective longitudinal cohort study was conducted using the Medicare claims data involving parts A, B, and D from 2013 to 2017. The study sample included older adults (65 years and older) diagnosed with AD and initiating ChEIs (donepezil, rivastigmine, or galantamine). The cumulative anticholinergic burden was calculated based on the Anticholinergic Cognitive Burden scale and patient-specific dosing using the defined daily dose over the 1 year follow-up period after ChEI initiation. Incremental anticholinergic burden levels were dichotomized into moderate-high (sum of standardized daily anticholinergic exposure over a year (TSDD) score ≥ 90) versus low-no (score 0-89). The Andersen Behavioral Model was used as the conceptual framework for selecting the predictors under the predisposing, enabling, and need categories. A multivariable logistic regression model was used to evaluate the predictors of high-moderate versus low-no cumulative anticholinergic burden. A multinomial logistic regression model was also used to determine the factors associated with patients having moderate and high burdens compared to low/no burdens.
The study included 222,064 older adults with AD with incident ChEI use (mean age 82.24 ± 7.29, 68.9% females, 83.6% White). Overall, 80.48% had some anticholinergic burden during the follow-up, with 36.26% patients with moderate (TSDD scores 90-499), followed by 24.76% high (TSDD score > 500), and 19.46% with low (TSDD score 1-89) burden categories. Predisposing factors such as age; African American, Asian, or Hispanic race; and need factors included comorbidities such as dyslipidemia, syncope, delirium, fracture, pneumonia, epilepsy, and claims-based frailty index were less likely to be associated with the moderate-high anticholinergic burden. The factors that increased the odds of moderate-high burden were predisposing factors such as female sex; enabling factors such as dual eligibility and diagnosis year; and need factors such as baseline burden, behavioral and psychological symptoms of dementia, depression, insomnia, urinary incontinence, irritable bowel syndrome, anxiety, muscle spasm, gastroesophageal reflux disease, heart failure, and dysrhythmia. Most of these findings remained consistent with multinomial logistic regression. CONCLUSION: Four out of five older adults with AD had some level of anticholinergic burden, with over 60% having moderate-high anticholinergic burden. Several predisposing, enabling, and need factors were associated with the cumulative anticholinergic burden. The study findings suggest a critical need to minimize the cumulative anticholinergic burden to improve AD care.
Talwar A
，Chatterjee S
，Sherer J
，Abughosh S
，Johnson M
，Aparasu RR
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Association of drug burden index with delirium in community-dwelling older adults with dementia: a longitudinal observational study.
The Drug Burden Index (DBI) is a validated tool for assessing the dose-dependent cumulative exposure to sedative and anticholinergic medications. However, the increased risk of delirium superimposed dementia (DSD) with high DBI levels has not yet been investigated.
This study aimed to examine the potential association between DBI scores and delirium in community-dwelling older adults with dementia.
A total of 1105 participants with cognitive impairment underwent a comprehensive geriatric assessment. Experienced geriatricians made the final diagnosis of delirium based on DSM-IV-TR and DSM-V. We calculated the DBI as the sum of all sedatives and anticholinergics taken continuously for at least four weeks before admission. Polypharmacy was defined as regular use of five or more medications. We classified the participants as having no exposure (DBI = 0), low exposure (0 < DBI < 1), and high exposure (DBI ≥ 1).
Of the 721 patients with dementia, the mean age was 78.3 ± 6.7 years, and the majority were female (64.4%). In the whole sample, low and high exposures to anticholinergic and sedative medications at admission were 34.1% (n = 246) and 38.1% (n = 275), respectively. Patients in the high-exposure group had higher physical impairment (p = 0.01), higher polypharmacy (p = 0.01), and higher DBI scores (p = 0.01). In the multivariate Cox regression analysis, high exposure to anticholinergic and sedative medications increased the risk of delirium 4.09-fold compared to the no exposure group (HR = 4.09, CI: 1.63-10.27, p = 0.01).
High exposure to drugs with sedative and anticholinergic properties was common in community-dwelling older adults. A high DBI was associated with DSD, highlighting the need for an optimal prescription in this vulnerable population.
The trial was retrospectively registered at ClinicalTrials.gov. Identifier: NCT04973709 Registered on 22 July 2021.
Katipoglu B
，Demircan SK
，Naharci MI
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Anticholinergic/Sedative Drug Burden and Subjective Cognitive Decline in Older Adults at Risk of Alzheimer's Disease.
Anticholinergic/sedative drug use, measured by the Drug Burden Index (DBI), has been linked to cognitive impairment in older adults. Subjective cognitive decline (SCD) may be among the first symptoms patients with Alzheimer's disease (AD) experience. We examined whether DBI values are associated with SCD in older adults at risk of AD. We hypothesized that increased DBI would be associated with greater SCD at older ages.
Two-hundred-six community-dwelling, English-speaking adults (age = 65 ± 9 years) at risk of AD (42% apolipoprotein ε4 carriers; 78% with AD family history) were administered a single question to ascertain SCD: "Do you feel like your memory is becoming worse?" Response options were "No"; "Yes, but this does not worry me"; and "Yes, this worries me." DBI values were derived from self-reported medication regimens using older adult dosing recommendations. Adjusting for relevant covariates (comorbidities and polypharmacy), we examined independent effects of age and DBI on SCD, as well as the moderating effect of age on the DBI-SCD association at mean ± 1 SD of age.
Both SCD and anticholinergic/sedative drug burden were prevalent. Greater drug burden was predictive of SCD severity, but age alone was not. A significant DBI*Age interaction emerged with greater drug burden corresponding to more severe SCD among individuals age 65 and older.
Anticholinergic/sedative drug exposure was associated with greater SCD in adults 65 and older at risk for AD. Longitudinal research is needed to understand if this relationship is a pre-clinical marker of neurodegenerative disease and predictive of future cognitive decline.
Margolis SA
，Kelly DA
，Daiello LA
，Davis J
，Tremont G
，Pillemer S
，Denby C
，Ott BR
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ResearchGate
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