Table 2.
Primary outcomes: summary of reported results
| Primary outcomes | Study | Frailty measure (mean/median) [SD] | Total number (%) of pre-frail/frail participants | AC exposure (description) | Outcome | Adjusted results* | Method of adjustment/controlling for confounding |
|---|---|---|---|---|---|---|---|
|
Physical impairment |
Bennett et al. [35] | Edmonton Frail Scale | Frail: 103 (50.4%) | One or more FRIDs (participants exposed to AC FRIDs on admission n = 131 [64.2%]; participants exposed to AC FRIDs on discharge n = 161 [78.9%]) | Falls | Total: OR 1.7 (95% CI 1.3–2.1)* | Age, sex, living status, comorbidity, ADL and IADL, fall risk factors and alcohol use |
| Fit: OR 2.4 (95% CI 1.3–6.1)* | |||||||
| Frail: OR 1.5 (95% CI 1.1–1.9)* | |||||||
| Functional decline | Total: OR 1.3 (95% CI 1.1–1.6)* | ||||||
| Fit: OR 1.4 (95% CI 0.9–2.0) | |||||||
| Frail: OR 1.2 (95% CI 1.0–1.5)* | |||||||
| 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) | Difficulty in chair stands | Full model: OR 4.2 (95% CI 2.0–8.7)* | 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 | |
| Poor balance | Full model: OR 4.9 (95% CI 2.0–12.0)* | ||||||
| Slow gait speed | Full model: OR 3.6 (95% 1.6–8.0)* | ||||||
| Poor mobility | Full model: OR 3.2 (95% CI 1.5–6.9)* | ||||||
| Poor upper extremity function | Full model: OR 2.7 (95% CI 1.3–5.4)* | ||||||
| Weak grip strength | Full model: OR 2.4 (95% CI 1.1–5.3)* | ||||||
| Cossette et al. [37] | Fried |
Pre-frail: 787 (43.9%) Frail: 67 (3.7%) |
ACB score (change in beta coefficient for every 1-unit change in ACB score) | PCS | Non-frail: ß −0.30 (95% CI − 0.54 to − 0.06)* | Parsimonious model: time, sex, age, number of co-morbidities, Geriatric Depression Scale | |
| Frail/pre-frail: ß − 0.61 (95% CI − 0.88 to − 0.33)* | |||||||
| 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) | Gait speed | − 0.13 (95% CI − 0.19 to − 0.08)* | Age, sex, education, comorbidities, self-reported status and cognitive impairment | |
| Chair stands test | 1.11 (95% CI 1.05–1.16)* | ||||||
| Grip strength (kg) | − 0.98 (95% CI − 2.05 to 0.08) | ||||||
| TUGT | 1.13 (95% CI 1.07–1.19)* | ||||||
| Gnjidic et al. [39] | Grip strength (mean 18.0 kg) [± 7.5] | Not reported | DBI (change in coefficient for every 1-unit change in DBI score) | SPPB | − 1.28 (95% CI − 2.53 to − 0.04)* | Age, sex, education, comorbidities, cognitive functioning, depression and sleep disturbance | |
| Grip strength (kg) | 0.10 (95% CI − 2.54 to 2.74) | ||||||
| Landi et al. [42] | Gait speed (m/s) | Not reported | Drugs that have demonstrated serum anticholinergic activity in literature (users of anticholinergics—dichotomised) | Gait speed (m/s) | Non-users AC drugs (mean): 0.49 (SE ± 0.01) | 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): 0.47 (SE ± 0.02) | |||||||
| SPPB | Non-users AC drugs (mean): 6.90 (SE ± 0.19)* | ||||||
| Users of AC drugs (mean): 6.19 (SE ± 0.25)* | |||||||
| Grip strength (kg) | Non-users AC drugs (mean): 31.33 (SE ± 0.81)* | ||||||
| Users of AC drugs (mean): 28.88 (SE ± 1.05)* | |||||||
| 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) | Grip strength (kg) | Cross-sectional: 0.73 (95% CI − 2.02 to 0.57) | Age, sex, high blood pressure, diabetes, heart disease, cancer, stroke | |
| Cohort at 3 years: − 0.78 (95% CI − 2.44 to 0.88) | |||||||
| One-leg balance (duration in seconds) | Cross-sectional: − 0.32 (95% CI − 4.57 to 3.93) | ||||||
| Cohort at 3 years: 1.89 (95% CI − 1.49 to 5.28) | |||||||
| Repetition standing (no. of times over 30 s) | Cross-sectional: − 1.30 (95% CI − 2.79 to 0.20) | ||||||
| Cohort at 3 years: 0.08 (95% CI − 1.77 to 1.93) | |||||||
| TUGT | Cross-sectional: 0.53 (95% CI − 2.46 to 3.52) | ||||||
| Cohort at 3 years: 0.38 (95% CI − 2.00 to 2.75) | |||||||
| Wilson et al. [46] |
Gait speed** (mean 0.56 m/s) [± 0.21] Grip strength** (mean 19.9 kg) [± 8.1] |
Not reported | DBI (stratified in to DBI < 1, DBI ≥ 1) | Falls | DBI < 1: IRR 1.61 (95% CI 1.17–2.23)* | Age, sex, history of falls, cognitive impairment, depressive symptoms, comorbidities, use of a walking aid, polypharmacy and incontinence | |
| DBI ≥ 1: IRR 1.90 (95% CI 1.30–2.78)* | |||||||
| Zia et al. [47] |
TUGT ≥ 13.5 s n = 168, 39.3% Reduced right grip strength (kg) n = 290, 67.8% Reduced left grip strength (kg) n = 313, 73.1% (≤ 20 kg women, ≤ 30 kg men) |
Not reported | ACB (characterised as ACB score ≥ 1) | Falls | Model 9: OR 1.4 (95% CI 0.8–2.4) | Reduced right grip strength + age, gender, number of comorbidities | |
| Model 10: OR 1.4 (95% CI 0.85–2.4) | Reduced left grip strength + age, gender, number of comorbidities | ||||||
| Model 11: OR 1.3 (95% CI 0.76–2.1) | TUGT ≥ 13.5 (s) + age, gender, number of comorbidities | ||||||
| Model 12: OR 1.2 (95% CI 0.7–2.1) | Functional reach ≤ 18 cm + age, gender, number of comorbidities | ||||||
| Cognitive dysfunction | 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) | Poor cognitive function (MMSE score ≤ 26) | Full model: OR 2.4 (95% CI 1.1–5.1)* | 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 |
| Cossette et al. [37] | Fried |
Pre-frail: 787 (43.9%) Frail: 67 (3.7%) |
ACB score (change in beta coefficient for every 1-unit change in ACB score) | MCS | Non-frail: ß 0.04 (95% CI − 0.16 to 0.24) | Parsimonious model: time, sex, age, number of comorbidities, Geriatric Depression Scale | |
| Frail/pre-frail: ß 0.30 (95% CI 0.04–0.57)* | |||||||
| 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) | MMSE | Cross-sectional: − 1.50 (95% CI − 2.96 to − 0.03)* | Age, sex, high blood pressure, diabetes, heart disease, cancer, stroke | |
| Cohort at 3 years: − 0.21 (95% CI − 1.78 to 1.35) | |||||||
| Change in frailty status | Jamsen et al. [41] | Fried |
Not reported; however, number of transitions reported: From pre-frail state: 603 stationary 172 to fit 114 to frail 200 to death From frail state: 73 stationary 35 to pre-frail 108 to death 3 to fit |
DBI (association with 1-unit increase in DBI) | Transitions between frailty states, and death (excluding transitions from fit state) | Pre-frail to fit: HR 0.90 (95% CI 0.59–1.36) | Age, diagnosis of dementia or mild cognitive impairment at baseline, comorbidity, education level, and living status |
| Pre-frail to frail: HR 1.03 (95% CI 0.76–1.40) | |||||||
| Pre-frail to death: HR 1.18 (95% CI 0.89–1.56) | |||||||
| Frail to pre-frail: HR 0.65 (95% CI 0.33–1.27) | |||||||
| Frail to death: HR 0.92 (95% CI 0.73–1.16) | |||||||
| Martinot et al. [43] | Strawbridge questionnaire (difficulty in 2 or more domains) |
Frailty (2012) = 1664 (14.0%) Frailty (2013) = 1766 (14.2%) Frailty (2014) = 1945 (16.6%) |
Exposed to at least 1 PIM using Laroche list (anticholinergics reported as, e.g., ‘tricyclic antidepressants’, ‘long-acting benzodiazepines’) | Changes in frailty state (frailty to fit state) | Anticholinergics: HR 0.84 (95% CI 0.64–1.09) | Age, gender, self-perceived social position, marital status, BMI, tobacco consumption, number of chronic diseases, and polypharmacy | |
| Other anticholinergics with questionable efficacy: HR 0.86 (95% CI 0.67–1.11) | |||||||
| Long-acting benzodiazepines: HR 0.89 (95% CI 0.70–1.14) | |||||||
| Concomitant use of ≥ 2 benzodiazepines: HR 0.93 (95% CI 0.61–1.41) | |||||||
| Concomitant use of ≥ 2 antidepressants: HR 0.57 (95% CI 0.25–1.32) | |||||||
| Prolonged use of benzodiazepines: HR 1.01 (95% CI 0.74–1.37) |
AC anticholinergic, ACB Anticholinergic Cognitive Burden scale, ADL Activities of Daily Living, BMI body mass index, CI confidence interval, DBI Drug Burden Index, FRID fall-risk–increasing drug, HR hazard ratio, IADL Instrumental Activities of Daily Living, IQR interquartile range, IRR incident rate ratio, MCS Mental Component Summary, MMSE Mini-Mental State Examination, OR odds ratio, PCS Physical Component Summary, PIM potentially inappropriate medicine, SPPB Short Physical Performance Battery, TUGT timed up and go test
*Represents significant associations determined as p ≤ 0.05
**Gait speed and grip strength were reported in a different study conducted by the first author, however, using the exact same cohort