TY - JOUR
T1 - Anticholinergic Exposure during Rehabilitation
T2 - Cognitive and Physical Function Outcomes in Patients with Delirium Superimposed on Dementia
AU - Kolanowski, Ann
AU - Mogle, Jacqueline
AU - Fick, Donna M.
AU - Campbell, Noll
AU - Hill, Nikki
AU - Mulhall, Paula
AU - Behrens, Liza
AU - Colancecco, Elise
AU - Boustani, Malaz
AU - Clare, Linda
N1 - Funding Information:
This is one of the first studies to examine the effects of anticholinergic medication exposure on rehabilitation outcomes in patients with delirium superimposed on dementia, a group at high risk for poor outcomes following hospitalization. We controlled for sociodemographic and health related factors (age, sex, education, ethnicity, comorbidity, dementia severity), allowing us to see the independent effect of anticholinergic medications on cognition, physical function, and length of stay. We found an independent and significant negative effect of clinically relevant anticholinergic medication use in the previous week on performance in two areas: Digit Span Backwards, a measure of attention and working memory, and the Barthel Index, a measure of physical function. There was no effect of anticholinergic medication use on delirium severity, and APOE status did not moderate any outcomes. We also found an association between use of these medications and longer length of stay but not discharge disposition. The cognitive outcomes we measured included several domain-specific cognitive functions as opposed to a single measure of global cognition such as the Mini-Mental State Exam, the outcome most often reported in prior research. 2 Our measurement approach likely improved specificity, and our findings point to the possibility that anticholinergic medications may not affect all cognitive domains equally. There are several other possible reasons for our cognitive findings. First, all participants were recovering from an acute illness and for the vast majority their delirium was resolving. The lack of effect on most cognitive domains may have been due to this general improvement in neurocognition. Second, the cognitive effects of anticholinergic medications might be difficult to detect in people with dementia, as we found in an earlier study 10 and as reported by Fox and colleagues. 27 Nonetheless, we did see an effect of these medications on Digit Span Backwards, a measure of attention and working memory. 28 These cognitive functions are critical for performance of everyday tasks, 29 and their impairment has been associated with reduced ability to carry out activities of daily living. 30 Our finding is important when considered in light of the results we report on physical function, and could adversely impact transitions from post-acute care to home, as we found and as discussed in the following. In addition to their cognitive effects, recent evidence indicates that medications with anticholinergic effects impact “global parameters” such as physical function in older adults. 31 Our findings are similar to and extend those of Koshoedo and colleagues, who found a negative effect of these medications on physical function in older adults who undergo orthopedic rehabilitation. 32 In that study less than 2% of the sample had a history of dementia, and in this study all participants had an adjudicated diagnosis of dementia. Worsening functional status during rehabilitation is an important risk factor for 30-day unplanned re-hospitalizations, 33 the rate of which is over 23% in post-acute care facilities. 34 For people with dementia, the loss of physical function is a major risk factor for permanent institutionalization, and contributes heavily to the national burden of healthcare costs. 35 Medicare expenditures for post-acute care are second only to inpatient hospital care, and length of stay drives much of this cost. A recent Office of the Inspector General report indicated that outcomes in post-acute care settings are often suboptimal and costly due to poor-quality treatment. 36 Problems with medication management were among the most prevalent reasons for the incurrence of harms that involved re-hospitalization or prolonged the length of stay. Our findings indicate that patients who received anticholinergic medications with significant clinical effects had a length of stay that was on average 4 days longer than patients not receiving these medications. These findings are similar to those of Lowery and colleagues, 31 who also found a negative impact of anticholinergic medications on hospital length of stay in their unadjusted analyses. The results of this study have important clinical implications for maximizing functional potential and reducing the costs of care for a growing number of people with dementia in need of rehabilitation. Many comorbid conditions have alternative therapeutic options with less negative impact on recovery. The detrimental effects of anticholinergic medications during post-acute care might be addressed by stopping unnecessary medications, 37 switching to an alternative medication with a lower anticholinergic effect, or using nonpharmacological interventions to address clinical problems that respond to them. 38 For example, in place of using antipsychotic medications, reversible contributions to delirium such as infection should be identified and appropriately treated; 12 in place of using diphenhydramine, sleep hygiene behaviors or a trial of melatonin can be attempted to reduce sleep problems; 39 and in place of using oxybutynin, a non-anticholinergic medication or prompted voiding might be instituted to address incontinence. 40 Although general de-prescribing trials have shown improvements in quality of life without significant adverse withdrawal effects, 41 de-prescribing studies of anticholinergics have shown anticholinergic reduction is possible but little is known about the effects on clinical outcomes, particularly among older adults with dementia. 42 Our findings and that of others also have implications across settings of care. Many medications with strong anticholinergic activity, such as diphenhydramine, are readily available over the counter and consumed by older adults in the community as an over-the-counter sleep aide. It is not known if anticholinergic-induced cognitive impairment is reversible, but recent evidence suggests that higher cumulative use of anticholinergic medications is associated with an increased risk for dementia. 43 The potential for these medications to impair cognition and function is an important public health message and a needed targeted area for education of both consumers and healthcare professionals. We acknowledge several limitations of this study. Our observational study used data from an ongoing clinical trial; unmeasured confounding variables could have biased our estimates. We did, however, control for a number of sociodemographic and health-related factors that have shown an association to our outcomes. Our sample size was not large and we conducted several tests relative to our outcomes increasing the potential for obtaining statistical significance by chance. We did, however, make use of multiple observations over time in our within-person analyses. These within-person analyses improve the precision of measurement so that even small effects could potentially be detected; and we acknowledge that some of our effects were small. We did not have data to establish the duration of anticholinergic medication use prior to post-acute care admission. We did, however, find that the vast majority of participants who received strong anticholinergic medications did so consistently across the study duration. We also did not have data on the dosage of medications administered. Lack of data on duration and dosage may have underestimated the true effect of strong anticholinergics in our analyses, as seen in recent work by Gray and colleagues. 43 There are also several strengths of the study. The sample was composed of individuals with delirium superimposed on dementia who were receiving rehabilitation, a growing population that has not been systematically studied to any extent. We used data on actual medication administration, not just prescription order data. Rather than using global measures of cognition to assess anticholinergic effects, we used measures of specific cognitive domains. Lastly, our study data were taken from an ongoing clinical trial that used reliable and valid measures. The goal of post-acute care is to optimize function. For people with dementia, appropriate anticholinergic medication management may help achieve rehabilitation goals and reduce the cost of care. AK and DMF acknowledge partial support from a National Institutes of Health (NIH)/National Institute of Nursing Research (NINR) grant, R01 NR012242 02: Reserve For Delirium Superimposed on Dementia (DSD). The contents of the paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH/NINR. NLH acknowledges partial support from a Hartford Foundation Claire M. Fagin Fellow Award. NC acknowledges receiving honoraria and grant support from Astellas Pharma, US. No other authors have any conflicts of interest or disclosures to report.
Publisher Copyright:
© 2015 American Association for Geriatric Psychiatry.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Objectives We examined the association between anticholinergic medication exposure and subsequent cognitive and physical function in patients with delirium superimposed on dementia during rehabilitation. We also examined length of stay and discharge disposition by anticholinergic medication exposure. Design In this secondary analysis we used control group data from an ongoing randomized clinical trial. Setting/Participants Participants with delirium and dementia were enrolled at admission to post-acute care. These 99 participants had a mean age of 86.11 (±6.83) years; 67.6% were women; 98% were Caucasian; and 33% were positive for at least one APOE e4 allele. Measures We obtained daily measures of cognitive and physical function using: Digit Span; memory, orientation and attention items from the Montreal Cognitive Assessment; CLOX; the Confusion Assessment Method; and the Barthel Index. Anticholinergic medication exposure was measured weekly using the Anticholinergic Cognitive Burden Scale. Results Using multilevel models for time we found that greater use of clinically relevant anticholinergic medications in the previous week reduced cognitive and physical function, as measured by Digit Span Backwards and the Barthel index, in the current week. There was no effect of anticholinergic medication use on delirium severity, and APOE status did not moderate any outcomes. Greater use of clinically relevant anticholinergic medications was related to longer length of stay but not discharge disposition. Conclusions For vulnerable older adults, anticholinergic exposure represents a potentially modifiable risk factor for poor attention, working memory, physical function, and greater length of stay during rehabilitation.
AB - Objectives We examined the association between anticholinergic medication exposure and subsequent cognitive and physical function in patients with delirium superimposed on dementia during rehabilitation. We also examined length of stay and discharge disposition by anticholinergic medication exposure. Design In this secondary analysis we used control group data from an ongoing randomized clinical trial. Setting/Participants Participants with delirium and dementia were enrolled at admission to post-acute care. These 99 participants had a mean age of 86.11 (±6.83) years; 67.6% were women; 98% were Caucasian; and 33% were positive for at least one APOE e4 allele. Measures We obtained daily measures of cognitive and physical function using: Digit Span; memory, orientation and attention items from the Montreal Cognitive Assessment; CLOX; the Confusion Assessment Method; and the Barthel Index. Anticholinergic medication exposure was measured weekly using the Anticholinergic Cognitive Burden Scale. Results Using multilevel models for time we found that greater use of clinically relevant anticholinergic medications in the previous week reduced cognitive and physical function, as measured by Digit Span Backwards and the Barthel index, in the current week. There was no effect of anticholinergic medication use on delirium severity, and APOE status did not moderate any outcomes. Greater use of clinically relevant anticholinergic medications was related to longer length of stay but not discharge disposition. Conclusions For vulnerable older adults, anticholinergic exposure represents a potentially modifiable risk factor for poor attention, working memory, physical function, and greater length of stay during rehabilitation.
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U2 - 10.1016/j.jagp.2015.07.004
DO - 10.1016/j.jagp.2015.07.004
M3 - Article
C2 - 26419732
AN - SCOPUS:84975882084
SN - 1064-7481
VL - 23
SP - 1250
EP - 1258
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
IS - 12
ER -
