Table 3.
Secondary outcomes: summary of reported results
| Secondary outcomes | Study | Frailty measure(s) (mean/median) [SD] | Total number (%) of pre-frail/frail participants | AC exposure (description) | Outcome | Adjusted results* | Method of adjustment/controlling for confounding |
|---|---|---|---|---|---|---|---|
| ADL | Cao et al. [36] | Difficulty in 2 or more functional domains out of a possible 8 (e.g. gait speed, chair stands, grip strength, mobility, balance) |
932 (100%) Assumed based on the inclusion criteria |
DBI (dichotomised ‘anticholinergic burden’ variable used to identify participants exposed to anticholinergic burden) | Disability in ADL | Full model: OR 3.4 (95% CI 1.7–6.9)* | Age, race, education, depression, arthritis, visual impairment, hearing impairment, hypertension, ischemic heart disease, congestive heart failure, pulmonary disease, osteoporosis, diabetes mellitus, cancer, spinal disc disease, hip fracture, spinal stenosis, Parkinson's disease, and peripheral arterial disease |
| Gnjidic et al. [38] |
Gait speed (mean 1.3 m/s) [± 0.4] Chair stands test (mean 16.7 s) [± 7.8] TUGT (mean 13.9 s) [± 9.3] Grip strength (mean 20.0 kg) [± 10.2] |
Not reported | DBI (change in coefficient where DBI score > 0) (dichotomised) | IADL score | − 0.61 (95% CI − 0.84 to − 0.39)* | Age, sex, education, comorbidities, self-reported status and cognitive impairment | |
| Barthel Index | − 3.21 (95% CI − 4.68 to − 1.75)* | ||||||
| Landi et al. [42] | Gait speed | Not reported | Drugs that have demonstrated serum anticholinergic activity in literature (users of anticholinergics—dichotomised) | ADL score (MDS-HC instrument) | Non-users AC drugs (mean): 1.23 (SE ± 0.12)* | Age, gender, smoking, physical activity level, living alone, BMI, dementia, congestive heart failure, lung diseases, diabetes, delirium, history of falls | |
| Users of AC drugs (mean): 1.68 (SE ± 0.15)* | |||||||
| IADL score (MDS-HC instrument) | Non-users AC drugs (mean): 2.71 (SE ± 0.11)* | ||||||
| Users of AC drugs (mean): 3.47 (SE a 0.14)* | |||||||
| Sato et al. [45] |
Grip strength (median 19.3 kg) IQR 15.3, 23.5 TUGT (median 12.6 s) IQR 10.5, 15.4 |
Not reported | DBI (change in coefficient for every 1-unit change in DBI score) | ADL score | Cross-sectional: − 0.95 (95% CI − 4.91 to 3.01) | Age, sex, high blood pressure, diabetes, heart disease, cancer, stroke | |
| Cohort at 3 years:− −6.31 (95% CI − 11.61 to − 1.01)* | |||||||
| IADL score | Cross-sectional: − 0.63 (95% CI − 0.99 to − 0.27)* | ||||||
| Cohort at 3 years: − 0.34 (95% CI − 0.79 to 0.10) | |||||||
| ADRs | Hanlon et al. [40] | Met 2 or more of 10 criteria for frailty (dependence in at least one ADL, stroke within 3 months, previous falls, difficulty ambulating, malnutrition, dementia, depression, unplanned admission in the last 3 months, prolonged bed rest, or incontinence) | 808 (100%) | Exposed to at least one anticholinergic drug/drug group (e.g. ‘anticholinergics’, ‘opioids’, ‘tricyclic antidepressants’) | Any ADRs | Benzodiazepines: HR 1.23 (95% CI 0.95–1.58) | Multivariate model derived using stepwise procedures using all candidate variables listed in Tables 1 and 2 of the article; however, final candidate variables chosen not reported |
| Warfarin: HR 1.51 (95% CI 1.22–1.87)* | |||||||
| Preventable ADRs | Warfarin (adjusted): HR 1.50 (95% CI 1.08–2.11)* | ||||||
| Hospitalisation/institutionalisation | Bennett et al. [35] | Edmonton Frail Scale | Frail: 103 (50.4%) | One or more FRIDs (participants exposed to AC FRIDs on admission = 131 [64.2%], participants exposed to AC FRIDs on discharge = 161 [78.9%]) | Hospitalisation | Total: OR 1.1 (95% CI 0.9–1.4) | Age, sex, living status, comorbidity, ADL and IADL, fall risk factors and alcohol use |
| Fit: OR 1.3 (95% CI 0.8–4.6) | |||||||
| Frail: OR 1.0 (95% CI 0.8–1.4) | |||||||
| Institutionalisation | Total: OR 1.3 (95% CI 1.1–1.6)* | ||||||
| Fit: OR 1.3 (95% CI 0.8–2.1) | |||||||
| Frail: OR 1.3 (95% CI 1.0–1.6)* | |||||||
| Death | Porter et al. [44] | Fried |
Pre-frail: 530 (45.9%) Frail: 420 (36.4%) |
Exposed to at least 1 PIM (anticholinergics identified using ACB scale and reported as, e.g., ‘tricyclic antidepressants’, ‘antipsychotics’, ‘benzodiazepines’) | Mortality |
Antipsychotics: Fit: HR 3.60 (95% CI 0.40–31.99) Pre-frail: HR 2.89 (95% CI 1.26–6.66)* Frail: HR 3.34 (95% CI 1.37–8.12) * |
Age, gender, MMSE score, care home residence and comorbidities. |
|
Anticholinergics: Fit: HR 1.29 (95% CI 0.16–10.61) Pre-frail: HR 1.05 (95% CI 0.61–1.79) Frail: HR 1.23 (95% CI 0.76–2.01) | |||||||
|
Tricyclic antidepressants: Fit: not reported Pre-frail: HR 1.84 (95% CI 0.98–3.44) Frail: HR 0.90 (95% CI 0.55–1.48) | |||||||
|
Benzodiazepines: Fit: HR 0.92 (95% CI 0.11–7.78) Pre-frail: HR 1.40 (95% CI 0.66–2.97) Frail: HR 0.43 (95% CI 0.21–0.86)* | |||||||
|
Other antidepressants: Fit: HR 0.86 (95% CI 0.23–3.20) Pre-frail: HR 1.12 (95% CI 0.67–1.89) Frail: HR 0.74 (95% CI 0.49–1.12) | |||||||
| Psychological functioning | Sato et al. [45] |
Grip strength (median 19.3 kg) IQR 15.3, 23.5 TUGT (median 12.6 s) IQR 10.5, 15.4 |
Not reported. Frailty not explicitly identified | DBI (change in coefficient for every 1-unit change in DBI score) | PGC | Cross-sectional: − 0.72 (95% CI − 1.79 to 0.35) | Age, sex, high blood pressure, diabetes, heart disease, cancer, stroke |
| Cohort at 3 years: − 1.00 (95% CI − 2.47 to 0.48) |
AC anticholinergic, ACB Anticholinergic Cognitive Burden scale, ADL Activities of Daily Living, ADR adverse drug reaction, BMI body mass index, DBI Drug Burden Index, FRID fall-risk–increasing drug, MDS-HC Minimum Data Set for Home Care Assessment instrument, HR hazard ratio, IADL Instrumental Activities of Daily Living, IQR interquartile range, MMSE Mini-Mental State Examination, OR odds ratio, PGC Philadelphia Geriatric Center Morale Scale, PIM potentially inappropriate medicine, TUGT timed up and go test
*Represents significant associations determined as p ≤ 0.05