Gromek 202253
United States
|
Cross-sectional
|
Nursing home patients with severe dementia in United States (USA).
|
Total, N = 37,087
Not receiving
Anticholinergics,
n = 31,478,
Receiving Anticholinergics, n = 5,609
|
6–10 and > 10 concurrent medications
|
co-prescribing of anticholinergics and ChEIs
|
Exposure to polypharmacy was associated with a higher likelihood of co-prescribing of anticholinergic and ChEIS (for 6–10 medications, AOR: 2.50, 95% CI: 2.33–2.67; for more than 10 concurrent drugs, AOR: 4.46, 95% CI: 4.04–4.94)
|
Age, sex, race/ethnicity, clinical health scales (Patient Health Questionnaire
[PHQ] score, Aggressive Behavior Scale23 score, comorbidities (cancer, heart failure, end-stage renal disease), presenting symptoms (UI, shortness of breath, poor appetite, weight loss, swallowing difficulty, limited prognosis)
|
Hanlon 201554
United States
|
Cross-sectional
|
65 years or older with Alzheimer’s diseases, Vascular Dementia, and other dementia admitted to the Veteran Affairs Community Living
Centres (CLCs) (Nursing homes)
|
Total, N = 1303
Mild to moderate Dementia, n = 1076
Severe Dementia, n = 227
|
5 + concurrent medications
|
Three types of suboptimal prescribing:
1) Underuse
2) Overuse
3) Inappropriate use
|
For patients with mild to moderate dementia, exposure to polypharmacy (5 + concurrent drugs) was not significantly associated with the increase of inappropriate medication use [ARRR: 1.12, 95% CI: 0.53–2.38]
On the other hand, for the patients with severe dementia, polypharmacy exposure (5 + concurrent drugs) was associated with the increase of inappropriate medication use (RRR: 0.29, 95% CI: 0.08–0.72)
|
Demographic factors (age, race, sex, and educational level), Site-level factors (urban/rural status, census region (Northeast, Midwest, South, West), facility size- small, medium, and large beds, and whether the patient resided in an Alzheimer’s/Dementia Special Care Unit. Health status (comorbidity index excluding dementia, other medication, Bipolar, Schizophrenia, Hypnotic use, Antidepressant use, Antipsychotic use, Memantine use)
|
Montastruc 201362
France
|
Prospective Cohort (4-year follow-up)
|
People with mild to moderate Alzheimer living at home cared by former caregivers
|
Total, N = 684 Polypharmacy, n = 299 non-polypharmacy, n = 385
|
≥ 5 concurrent medications
|
Potentially Inappropriate Medication (PIM)
|
Exposure to polypharmacy was associated with the increase of PIM (AOR: 3.6, 95% CI: 2.6–4.5)
|
Sex, monthly household income (Euros), education level, dementia status (MMSE score), ADL score, NPI score and MNA score modified
|
Nørgaard 201757
|
Cross-sectional
|
All residents ≥ 65 years diagnosed with dementia in in- and out-patient
|
Total, N = 34,553
Home living patients, n = 17,473
Nursing home residents, n = 17,080
|
5–9 and ≥ 10 concurrent medications
|
Prescribing of antipsychotics and other psychotropics
|
Polypharmacy exposure (5–9 and ≥ 10 drugs) were associated with the increased likelihood of prescribing antipsychotic and other psychotropic drugs (For 5–9 medications, AOR: 1.54, 95% CI: 1.15–2.08; for ≥10 medications, AOR: 1.88, 95% CI: 1.39–2.55)
|
Age group, sex, Charlson Comorbidity Index, living status, time since dementia diagnosis, number of drugs in 2011, and prior psychiatric disorder.
|
Rausch 202066
Germany
|
Retrospective cohort study (4-year follow-up)
|
≥ 65 year people with and without all-cause dementia living in nursing home
|
Total, N = 67,328
with dementia, n = 29,052) and without dementia, n = 38,276
|
1) Minor Polypharmacy: 5–9 concurrent medications
2) Excessive Polypharmacy: ≥ 10 concurrent medications
|
Medications of questionable benefits
|
Polypharmacy exposure was significantly associated with medication of questionable benefits [AOR: 2.11 (1.78–2.51) (For 5–9 drugs) and AOR: 4.03 (3.40–4.77) (For ≥ 10 drugs)]
|
Age at death, sex, number of medications prescribed, length of stay in nursing home, and level of nursing care
|
Yoon 202259
South Korea
|
Cross-sectional
|
≥ 65 year PwD in outpatient department of a university hospital
|
n = 2100
|
≥ 5 concurrent medications
|
Potentially Inappropriate Medications
|
Polypharmacy exposure was significantly associated with increased prescribing of Potentially Inappropriate Medications Associated with Dementia Exacerbation (DPIM) (AOR: 5.146 (3.912- 6.768), p < 0.001)
|
Age, Charlson Comorbidity Index, marital status, BMI, prior hospitalizations, year of admission
|
Consequence
|
Adverse Drug Reaction (ADR)
|
Imai 202061
Japan
|
Cross-sectional
|
People living with all-cause dementia from home, community, and nursing home care (mean age 80.1 years)
|
Total, N=
0–9 daily concurrent medications, n = 863
10 or more medications, n = 530,
10 or more concurrent drug, n = 231
|
10 or more types of drugs per day
|
Adverse Drug Reactions (ADR)
|
Polypharmacy exposure was significantly associated with increased incidents of ADR (AOR: 1.51, 95% CI: 1.04–2.19)
|
Age and level of nursing home care.
|
Kanagaratnam 201463
France
|
prospective cohort (1 year 6 months follow-up)
|
In total, 293 patients aged 82 ± 8 years living mostly in home and a few in hospital care diagnosed with all type dementia with mild, moderate and severe dementia in the University Hospital of Reims, France.
|
Total, N = 293
Polypharmacy: 245
Non-polypharmacy: 48)
|
≥ 5 concurrent mediations/day
|
Adverse Drug Reaction (ADR), and Serious ADR
|
In univariate analysis, exposure to polypharmacy was associated with increased ADR events (UOR: 5.6, 95% CI: 1.7–18.8) and Serious ADR (UOR: 3.6, 95% CI: 0.8–15.5).
|
ADR: age, sex, living in an institution, dependent on at least 1 ADL, dependent on at least 1 IADL; Severe ADR: age, sex, dependent on at least 1 ADL,
and depression.
|
Kanagaratnam 201771
France
|
prospective cohort (1 year 6 months follow-up)
|
Patients aged 82 ± 8 years living mostly in home and a few in hospital care diagnosed with all type dementia with mild, moderate and severe dementia in the University Hospital of Reims, France.
|
Total, N = 293
Polypharmacy: 245
Non-polypharmacy: 48)
|
≥ 5 concurrent mediations/day
|
Adverse Drug Reaction (ADR) and
Serious Adverse Drug Reaction
|
Polypharmacy exposure was associated with increased event of ADR (AOR: 4.0, 95% CI: 1.1–14.1) in unadjusted model.
|
ADR: Age, sex, living in an institution, dependent on at least 1 ADL, dependent on at least 1 IADL; Severe ADR: age, sex, dependent on at least 1 ADL,
and depression.
|
Consequence
|
Hospitalization
|
Afonso-Argilés 202068
8 European Countries (Estonia, Finland,
France, Germany, Netherlands, Spain, Sweden, and the
United Kingdom).
|
Cross-sectional
|
People living in Nursing Homes (for 1–3 months), institutional care, and taking cared by informal caregivers diagnosed with Dementia.
|
Nursing Home (n = 646), Home Care (n = 1054)
|
≥ 5 concurrent medications
|
1) Emergency Department Admission (EDA)
2) Hospital Admission (HA)
|
Polypharmacy exposure was associated with increased rate of having at least one emergency department admission (EDA) or hospital admission (HA) in nursing home patients: AOR: 1.96, 95% CI: 1.03–3.75), and for the home-care patients, AOR: 2.48, 95% CI: 1.70–3.62)
|
Age, Sex, CCI, S-MMSE, Katz Index, NPI-Q scores, ZBI, weight loss, falls and setting.
|
Leung 2013
Hong-kong
|
Prospective Cohort (1-year follow-up)
|
Newly admitted patients to the 10 long-term care facilities diagnosed with Alzheimer’s disease residents aged 82.74 (SD = 8.07)
|
Total, N = 169
|
≥ 3 concurrent medications
|
Hospitalization and mergency room use
|
Polypharmacy was significantly associated with increased frequency of hospitalization and emergency room use during admission [hospitalization (β = 0.081, p < 0.001), emergency room use (β = 0.091, p < 0.001)], and one year follow-up [hospitalization (β = 0.058, p < 0.001), emergency room use (β = 0.077, p < 0.001)]
|
cognition, ADL
|
Mueller 20186
United Kingdom
|
Retrospective cohort (2-year follow-up)
|
65 or older first diagnosed with Dementia in outpatient care
|
Total, N = 4668
|
4–6 or ≥ 7 concurrent medications
|
Emergency department attendance, hospital admissions and mortality
|
Polypharmacy (4–6 concurrent drugs) was significantly associated with increased rate of emergency department attendance [Adjusted for age, gender, and MMSE score, AHR: 1.27, 95% CI: 1.16–1.39 and Full adjusted HR: 1.20, 95% CI: 1.09–1.31)], hospitalization [for age, gender, and MMSE score, AHR: 1.21, 95% CI: 1.11–1.32, and Full adjusted HR: 1.12, 95% CI: 1.02–1.22].
Polypharmacy (≥ 7 concurrent drugs) was also significantly associated with increased rate of emergency department attendance [for age, gender, and MMSE score, AHR: 1.54, 95% CI: 1.39–1.71, and Full adjusted HR: 1.35, 95% CI: 1.21–1.51], hospitalization [for age, gender, and MMSE score, AHR: 1.63, 95% CI: 1.48–1.79, and Full adjusted HR: 1.32, 95% CI: 1.19–1.47].
|
age, sex, ethnicity, marital status, MMSE score, deprivation score, HoNOS65 + physical illness problem score, number of co-morbid non-cognitive mental health problems (all at time of dementia subtypes.
|
Renom-Guiteras 201869
Eight European countries (Estonia, Finland, France, Germany, Netherlands, Sweden, Spain, United Kingdom)
|
Prospective cohort study (2 year 5 months)
|
European countries who were wither newly admitted to an institutional long-term care or living in homecare, but in risk of admission to any long-term care facility (mean age 83 ± 6.6).
|
Total, N = 2004
|
5–9 and ≥ 10 concurrent medications
|
Hospitalization and mortality
|
Polypharmacy was significantly associated with increased hospitalization for both 5-<10 concurrent drugs, AOR: 2.04, 95% CI: 1.41–2.93, and ≥ 10 concurrent drugs, AOR: 4.37, 95% CI: 2.66–7.18.
|
age, sex, functional status and comorbidity.
|
Consequence
|
Mortality
|
Mueller 20186
United Kingdom (UK)
|
Retrospective cohort (2-year follow-up)
|
65 or older first diagnosed with Dementia in outpatient care
|
Total, N = 4668
|
4–6 and ≥ 7 concurrent medications
|
Mortality, Emergency department attendance, and hospital admissions
|
Polypharmacy was associated with increased risk of mortality [For 4–6 concurrent drugs, Adjusted for age, sex, and MMSE, HR: 1.37 (1.20–1.57), p < 0.01, and fully adjusted, AHR: 1.29 (1.11–1.49), p < 0.01., Adjusted for age, sex, and MMSE score and ≥ 7 concurrent drugs, HR: 1.61(1.38–1.87), p < 0.01, and fully adjusted HR: 1.39 (1.17–1.66), p < 0.01.]
|
age, sex, ethnicity, marital status, MMSE score, deprivation score, HoNOS65 + physical illness problem score, number of co-morbid non-cognitive mental health problems (all at time of dementia subtypes
|
Renom-Guiteras 201869
Eight European countries (Estonia, Finland, France, Germany, Netherlands, Sweden, Spain, United Kingdom)
|
Prospective cohort study (2 year 5 months)
|
People with dementia in eight European countries who were wither newly admitted to an institutional long-term care or living in homecare, but in risk of admission to any long-term care facility (mean age 83 ± 6.6).
|
Total, N = 2004
|
5–9 and ≥ 10 concurrent medications
|
Mortality and hospitalization
|
Polypharmacy defined as 5-<10 concurrent regular drugs was significantly associated with decreased risk of mortality [AOR: 0.60 (0.36–0.98)], but polypharmacy defined as ≥ 10 concurrent drug was not significantly associated with mortality [AOR: 0.92, 95% CI: 0.45–1.90].
|
age, sex, functional status and comorbidity.
|
Veedfald 202158
Denmark
|
Prospective Cohort (0–11 years follow-up)
|
Patients aged ≥ 65 years with diagnosed with all-cause dementia from nationwide register.
|
N = 6550
(0 drugs, n = 135, 1–4 drugs, n = 1878, 5–9 drugs, n = 3218, ≥ 10 drugs, n = 1288, Missing data: 31)
|
5–9 and ≥ 10 concurrent medications
|
All-cause mortality
|
Polypharmacy exposure was not significantly associated with mortality [AHR (5–9 Medications): 0.91 (0.72–1.15), and AHR (≥ 10 medication): 1.02 (0.80–1.30)]
|
adjusting for age, marital status, Charlson Comorbidity Index, BMI, prior hospitalizations, year of admission
|
|
Other Outcome
|
Lau 201155
United States (USA)
|
Retrospective Cohort (4- year follow-up)
|
Community dwelling (ie, living in an
independent family residence or retirement community) patients aged 65 and older with all type Dementia.
|
1994
|
1) ≤ 5 concurrent medications excluding herbal, vitamins, and topical agents
2) ≤ 7 concurrent medications (for sensitivity analysis)
|
Decline of functional status
|
participants having 5 or more concurrent medications were more likely to have functional decline than participants having < 5 medications (UOR: 1.23, 95% CI: 1.01–1.49); AOR: 1.27, 95% CI: 1.03–1.56).
|
age, sex, race/ethnicity, number of comorbid conditions, CDR global score, time between visits, and baseline functional status
|
Hanlon 201554
the United States (USA)
|
Cross-sectional
|
65 years or older with Alzheimer’s diseases, Vascular Dementia, and other dementia admitted to the Veteran Affairs Community Living
Centres (CLCs) (Nursing homes)
|
Mild to moderate Dementia (n = 1076)
Severe Dementia:
(n = 227)
Total: 1303
|
5 + concurrent medications
|
Three types of suboptimal prescribing:
1) Underuse
2) Overuse
3) Inappropriate use
|
For patients with mild to moderate dementia, polypharmacy exposure (5 + concurrent drugs) was significantly associated with the increased rate of medication underuse [ARRR: 2.72, 95% CI: 1.76–4.21]. For the patients with severe dementia, polypharmacy exposure (5 + concurrent drugs) was not significantly associated with medication over ruse (ARRR: 0.67, 95% CI: 0.26–1.70.
|
Demographic factors (age, race, sex, and educational level), Site-level factors (urban/rural status, census region (Northeast, Midwest, South, West), facility size- small, medium, and large beds, and whether the patient resided in an Alzheimer’s/Dementia Special Care Unit. Health status (comorbidity index excluding dementia, other medication, Bipolar, Schizophrenia, Hypnotic use, Antidepressant use, Antipsychotic use, Memantine use)
|
Hoffmann 201165
|
Cross Sectional
|
First diagnosis with dementia from the included in a statutory health insurance company of Germany (mean age: 78.7+- 7.4)
|
n = 1,848
|
Number of concurrent medications were categorized into 4 quartiles (Q1: 0–6, Q2: 7–9, Q3: 10–13, and Q4: 14 + medications). 14 + medication group was considered as reference group.
|
Prescription of ChEIs
|
Any type of polypharmacy was not significantly associated (considering quartile-4, 14 + drugs, as reference group) with co-prescribing of ChEIs (for quartile-01 (0–6 drugs), AOR: 0.93, 95% CI: 0.58–1.49), for quartile-2 (7–9 drugs), AOR: 1.03, 95% CI: 0.64–1.65, and for Quartile-3 (10-13drugs), AOR: 0.79, 95% CI: 0.49–1.28, quartile-4: 14 + medications as reference group
|
Age, sex, area of residence (urban, rural), quartile of number of prescribed medications, level of care dependency, number of symptom complexes characterizing geriatric patients, and number of contacts to neurologists/psychiatrists in the incidence year
|
Janssen 202070
The Netherlands
|
Retrospective cohort (mean follow-up time was 1.9‒ 3.1 years)
|
Community dwelling people diagnosed with dementia.
|
N = 11,012
|
≤ 5 concurrent medications
|
Care durations among the PwD with and without polypharmacy
|
Total institutional care duration of the PwD among the polypharmacy and non-polypharmacy groups males and females were found almost same (total care duration of male PwD of 65 years old with polypharmacy: 10.2, 95% CI: 9.6‒10.7, and total care duration of male PwD of 65 years old without polypharmacy: 10.4, 95% CI: 9.7‒11.1; total care duration of female PwD of 65 years old with polypharmacy: 13.0, 95% CI: 12.3‒13.7, and total care duration of female PwD of 65 years old without polypharmacy: 12.9, 95% CI: 12.2‒13.8).
Total institutional are duration was less to the people exposed to polypharmacy compared to those not exposed to polypharmacy among all the study population (care duration, polypharmacy: 50.2, non-polypharmacy: 52.1 months)
|
Model 1: age and sex only. Model 2: with dementia medication, and living situation
|
Lalic 201660
Australia
|
Cross-sectional
|
PwD aged ≥ 65 in residential aged care facilities
|
n = 383 (Polypharmacy, n = 243, non-polypharmacy, n = 140)
|
≤ 9 concurrent medications
|
Quality of Life
|
Polypharmacy neither in adjusted nor in unadjusted model was associated with increase of decrease of QoL (UOR: 0.175, p = 0.20, AOR: −0.020, 95%, p = 0.78)
|
age, sex comorbidity, ADL and dementia
severity, Charlson’s Comorbidity Index (CCI), Activities of daily living
|
Renom-Guiteras 201869
|
Prospective cohort study (2 year 5 months)
|
European countries who were wither newly admitted to an institutional long-term care or living in homecare, but in risk of admission to any long-term care facility (mean age 83 ± 6.6).
|
n = 2004
|
5–9 and ≥ 10 concurrent medications
|
Fall-related Injury
|
Polypharmacy was not associated with fall related injuries.
[AOR for 5-<10 concurrent drugs: 1.26 (0.85–1.86), and AOR for ≥ 10 concurrent drugs: 1.62 (0.93–2.87)]
|
confounding variables, including age, sex, functional status and comorbidity.
|
Soysal 201956
The United Kingdom (UK)
|
Retrospective Cohort (1 year before and
36 months after the diagnosis of dementia)
|
First clinically diagnosed people with dementia (Alzheimer’s disease, vascular dementia,
Lewy body dementias, and unspecified or other dementia)
|
n = 12148
|
Polypharmacy: 5–9 concurrent medications and excessive polypharmacy: 10 or more medications
|
Cognitive Decline
|
Polypharmacy did not predict any cognitive decline (0–6 months after and 12 − 0 months before dementia diagnosis for 5–9 medications, adjusted β: 0.61, 95% CI: −0.23 to 1.45 and ≥10 medications, adjusted β: −1.22, 95% CI: −2.83 to 0.38, 6–36 months after and 12–0 months before dementia diagnosis for 5–9 medications, adjusted β: −0.06, 95% CI:−0.65 to 0.54, for ≥ 10 medications, adjusted β: −1.23, 95% CI: −3.22 to 0.74]
|
age, sex, ethnicity, marital status, deprivation score, dementia subtype, HoNOS65 + symptoms scores (agitation, hallucinations and/or delusions, self-injury, substance use, depressed mood, physical illness), HoNOS65 + functional problem scores (activities of daily living, living conditions, occupational/recreational activities, social relationships), hospitalization prior to dementia diagnosis, and AchEI prescription.
|