Polypharmacy Among Older Adults With Dementia Compared With Those Without Dementia in the United States

Matthew E. Growdon MD, MPH; Siqi Gan MPH; Kristine Yaffe MD; Michael A. Steinman MD

J Am Geriatr Soc. 2021;69(9):2464-2475.

Abstract and Introduction

Abstract

Background/Objectives: In older persons with dementia (PWD), extensive medication use is often unnecessary, discordant with goals of care, and possibly harmful. The objective of this study was to determine the prevalence and medication constituents of polypharmacy among older PWD attending outpatient visits in the United States.

Design: Cross-sectional analysis.

Setting and Participants: PWD and persons without dementia (PWOD) aged ≥65 years attending outpatient visits recorded in the nationally representative National Ambulatory Medical Care Survey (NAMCS), 2014–2016.

Measurements: PWD were identified as those with a diagnosis of dementia on the NAMCS encounter form and/or those receiving an anti-dementia medication. Visits with PWD and PWOD were compared in terms of sociodemographic, practice/physician factors, comorbidities, and prescribing outcomes. Regression analyses examined the effect of dementia diagnosis on contributions by clinically relevant medication categories to polypharmacy (defined as being prescribed ≥5 prescription and/or nonprescription medications).

Results: The unweighted sample involved 918 visits for PWD and 26,543 visits for PWOD, representing 29.0 and 780 million outpatient visits. PWD had a median age of 81 and on average had 2.8 comorbidities other than dementia; 63% were female. The median number of medications in PWD was eight compared with three in PWOD (p < 0.001). After adjustment, PWD had significantly higher odds of being prescribed ≥5 medications (AOR 3.0; 95% CI: 2.1–4.3) or ≥10 medications (AOR 2.8; 95% CI: 2.0–4.2) compared with PWOD. The largest sources of medications among PWD were cardiovascular and central nervous system medications; usage from other categories was generally elevated in PWD compared with PWOD. PWD had higher odds of receiving at least one highly sedating or anticholinergic medication (AOR 2.5; 95% CI: 1.6–3.9).

Conclusion: In a representative sample of outpatient visits, polypharmacy was extremely common among PWD, driven by a wide array of medication categories. Addressing polypharmacy in PWD will require cross-cutting and multidisciplinary approaches.

Introduction

Polypharmacy is associated with a host of adverse outcomes among older adults, including drug reactions and use of potentially inappropriate medications (PIMs), significant morbidity such as falls and cognitive decline, and mortality.^[1–4] Although many medications may be prescribed in line with chronic disease-specific guidelines, some medications have limited value, are discordant with goals of care, and are associated with more harm than benefit in older adults.^[5] This challenging clinical and public health situation is encapsulated by the care of people with dementia (PWD), a growing population and widely recognized health system priority in the United States and internationally.^[6,7] People living with Alzheimer's disease and related dementias often have multimorbidity^[8] and are particularly vulnerable to the occurrence and risks of polypharmacy given the potential for communication barriers between providers, patients, and caregivers, cognitive and functional changes associated with the disease, and evolving goals of care in the context of reduced life expectancy.^[9] Moreover, specific medications including anticholinergic and sedative medications have been linked with increased risk of hospitalization and mortality among PWD.^[10] As a result, recent literature has highlighted the importance of safe prescribing^[11] and the promise of deprescribing interventions^[12] for this vulnerable population.

Surprisingly, nationally representative data regarding overall prescribing practices among the estimated 3.4 million PWD living in the community^[13] in the United States are sparse.^[1,9] Studies have documented high prevalence of polypharmacy and exposure to PIMs among PWD, but these primarily represent nursing home settings and more advanced stages of dementia or do not involve a random national sample of PWD, limiting generalizability.^[9,14–18] Additionally, many studies have focused specifically on the role of central nervous system-active polypharmacy^[19] or PIMs such as anticholinergic medications in prescribing practices related to PWD.^[20–22] Given that the majority of adverse drug reactions affecting older adults result from medications that are not necessarily considered inappropriate in this age group,^[23,24] a broad perspective on the full breadth of medication categories contributing to polypharmacy among PWD is necessary.

Using nationally representative data, we aimed to profile polypharmacy among PWD by comparing polypharmacy prevalence and medication categories contributing to polypharmacy between older adults with dementia and people without dementia (PWOD) attending outpatient visits in the United States. Additionally, we aimed to compare exposure to highly anticholinergic and sedating medications in these groups. We explored associations between the diagnosis of dementia and both polypharmacy and prescribing of clinically relevant medication categories, accounting for factors including age, sex, and comorbidity burden. Better understanding of the overall medication use of community-dwelling PWD is critical to designing clinical and health system interventions to reduce potentially unnecessary, harmful, or goal-discordant medication exposure in this population.

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Table 1. Characteristics of people ≥65 years old with and without dementia attending outpatient visits in the United States, 2014–2016
Characteristic	Persons with dementia 29.0 million visits (weighted)	Persons without dementia 780 million visits (weighted)	p value for comparison
Age
65–74	22% (0.17–0.29)	55% (0.54–0.56)
75–84	40% (0.32–0.49)	33% (0.32–0.34)
≥85	38% (0.28–0.49)	12% (0.11–0.13)	p < 0.001
Female sex	63% (0.58–0.68)	56% (0.55–0.57)	p = 0.01
Race
White	89% (0.82–0.93)	85% (0.82–0.87)
Black	6% (0.04–0.10)	9% (0.08–0.10)
Other	5% (0.02–0.13)	6% (0.04–0.10)	p = 0.43
Hispanic or Latino ethnicity
Not Hispanic or Latino	85% (0.77–0.90)	90% (0.88–0.92)
Hispanic or Latino	15% (0.10–0.23)	10% (0.08–0.12)	p = 0.05
Specialty of clinician
Primary Care	59% (0.50–0.67)	38% (0.35–0.41)
Medical Specialty	28% (0.22–0.35)	34% (0.31–0.38)
Surgical	13% (0.10–0.17)	28% (0.26–0.31)	p < 0.001
Seen before in practice	88% (0.81–0.92)	88% (0.87–0.89)	p = 0.81
# visits with sampled physician's practice in past 12 months (among visits to primary care clinics)
0	10% (0.04–0.22)	10% (0.09–0.13)
1–2	20% (0.13–0.29)	27% (0.24–0.31)	p = 0.32
3–5	34% (0.26–0.43)	34% (0.31–0.37)
6+	36% (0.25–0.48)	29% (0.25–0.32)
# visits with sampled physician's practice in past 12 months (among visits to non-primary care clinics)
0	23% (0.18–0.29)	22% (0.21–0.24)	p = 0.96
1–2	35% (0.28–0.42)	33% (0.31–0.35)
3–5	24% (0.19–0.31)	26% (0.24–0.28)
6+	18% (0.13–0.25)	19% (0.17–0.20)
Region of country
NE	12% (0.08–0.17)	20% (0.18–0.22)
Midwest	18% (0.13–0.24)	20% (0.18–0.22)
South	43% (0.34–0.53)	35% (0.32–0.38)
West	27% (0.17–0.40)	25% (0.21–0.29)	p = 0.07
Source of payment
Private	10% (0.06–0.17)	15% (0.14–0.17)
Public	84% (0.76–0.89)	79% (0.77–0.81)
Self-pay/other	6% (0.03–0.11)	6% (0.05–0.07)	p = 0.21
# of comorbidities
0	13% (0.09–0.19)	17% (0.15–0.18)
1	15% (0.11–0.21)	21% (0.20–0.23)
2	22% (0.18–0.28)	21% (0.20–0.22)
3	19% (0.15–0.25)	18% (0.17–0.19)
≥4	30% (0.22–0.38)	23% (0.21–0.25)	p = 0.08
Number of medications (median, IQR)	8 (4–13)	3 (1–8)	p < 0.001
Polypharmacy
≥5 medications	72% (0.64–0.79)	44% (0.42–0.47)	p < 0.001
≥10 medications	43% (0.34–0.54)	20% (0.18–0.22)	p < 0.001

Notes: All results are adjusted for weights and survey design to produce nationally representative estimates; the unweighted sample included 918 visits for PWD and 26,543 visits for PWOD. For all percentages, the denominator is total number of visits. The only exception is for the number of repeat visits in the past 12 months: because this information is only available for the sampled physician's practice, this variable is presented separately for primary care and non-primary care clinics, and the denominators in those cases refer to the total number of visits involving a primary care physician or visits involving a non-primary care physician. Pearson Chi-squared tests were used for categorical variables and t-tests for continuous variables.

Table 2. Medication use in people with versus without dementia, adjusted for age, sex, and comorbidity burden
Medication category	Mean number of medications in use per visit		Probability of visit with at least one prescribed medication in use
Medication category	Persons with dementia	Persons without dementia	Persons with dementia	Persons without dementia
Central nervous system	2.0 ± 0.10	0.46 ± 0.02	85% (0.81–0.90)	27% (0.25–0.28)
Cholinesterase inhibitors	0.57 ± 0.04	—	56% (0.50–0.63)	—
Antidepressants	0.42 ± 0.04	0.15 ± 0.01	34% (0.28–0.40)	11% (0.10–0.12)
Anxiolytics, sedatives, hypnotics	0.26 ± 0.04	0.15 ± 0.01	22% (0.14–0.30)	12% (0.11–0.14)
Antiepileptics	0.24 ± 0.04	0.07 ± 0.004	19% (0.12–0.27)	6% (0.05–0.07)
Memantine	0.23 ± 0.03	—	23% (0.17–0.29)	—
Antipsychotics	0.10 ± 0.02	0.01 ± 0.002	9% (0.05–0.12)	1% (0.008–0.01)
Cardiovascular	2.0 ± 0.12	1.7 ± 0.05	73% (0.66–0.79)	56% (0.53–0.60)
Vitamins and supplements	1.1 ± 0.09	0.76 ± 0.03	51% (0.45–0.57)	33% (0.31–0.35)
Other	0.88 ± 0.09	0.76 ± 0.03	46% (0.39–0.52)	42% (0.40–0.45)
Gastrointestinal	0.66 ± 0.08	0.40 ± 0.02	41% (0.31–0.50)	26% (0.24–0.29)
Analgesic	0.51 ± 0.06	0.30 ± 0.01	33% (0.27–0.39)	22% (0.20–0.23)
Opioids	0.25 ± 0.04	0.17 ± 0.01	20% (0.14–0.26)	15% (0.13–0.16)
Diabetes	0.32 ± 0.07	0.22 ± 0.01	14% (0.10–0.19)	10% (0.09–0.11)
Hormone/metabolic	0.31 ± 0.03	0.33 ± 0.02	26% (0.21–0.31)	26% (0.24–0.28)
Respiratory	0.27 ± 0.04	0.25 ± 0.01	17% (0.11–0.22)	14% (0.13–0.15)
Genitourinary	0.27 ± 0.04	0.15 ± 0.007	19% (0.11–0.27)	9% (0.08–0.10)
Coagulation modifiers	0.24 ± 0.04	0.16 ± 0.008	18% (0.14–0.22)	13% (0.11–0.14)

Notes: Results reflect the predicted mean number of prescription and nonprescription medications in use per visit and the predicted probabilities of taking at least one medication by medication category for a sample patient whose age, sex, and comorbidity count correspond to average values observed among PWD. Selected subgroups for the central nervous system and analgesic categories are provided; these do not represent all possible medication subgroups within those groups. All results are adjusted for weights and survey design to produce nationally representative estimates. Standard errors are presented for means and 95% confidence intervals are presented for percentages. Nonparametric Wilcoxon signed-rank tests support the predominance of higher mean number of medications in use per visit (p = 0.007) and higher predicted probabilities of taking at least one medication by category (p < 0.001) among PWD compared with PWOD.

Table 3. Mean number of highly anticholinergic and sedating medications among persons with versus without dementia
Category	Persons with dementia 29.0 million visits (weighted)	Persons without dementia 780 million visits (weighted)	p value for comparison
Number of highly sedating medications	0.47 ± 0.08	0.19 ± 0.01	p = 0.001
Number of highly anticholinergic medications	0.17 ± 0.03	0.09 ± 0.004	p < 0.001
Number of highly anticholinergic and sedating medications	0.64 ± 0.09	0.28 ± 0.01	p < 0.001

Notes: Means are presented with standard errors. The unweighted sample included 918 visits for PWD and 26,543 visits for PWOD.

Table 4. Most commonly prescribed highly anticholinergic or highly sedating medications among persons with dementia attending outpatient visits
Medication category	Average number of medications prescribed per visit	Number of unique outpatient visits from 2014 to 2016 in which medication was recorded as continued or newly prescribed
Benzodiazepines	0.17 ± 0.04	5,013,092
Gabapentinoids	0.17 ± 0.04	4,878,901
Antipsychotics	0.07 ± 0.01	2,054,807
Urinary antispasmodics	0.07 ± 0.02	2,029,820
Antihistamines	0.04 ± 0.01	1,123,114

Notes: Means are presented with standard errors. The table includes any medication groups or specific medications among the most commonly prescribed highly anticholinergic or sedating medications in which the relative standard error was less than 30% and therefore was considered reliable per NCHS guidance. Results are adjusted for weights and survey design to produce nationally representative estimates.

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Polypharmacy Among Older Adults With Dementia Compared With Those Without Dementia in the United States

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