Table 1.
Characteristics of included studies
| Study | Study design | Year | Country | Healthcare setting | Sample size Study duration |
Mean [median] age | % male (%) | Anticholinergic exposure | Frailty measure (threshold used by study authors) | Outcomes reported |
|---|---|---|---|---|---|---|---|---|---|---|
| Bennett et al. [35] | Prospective cohort | 2014 | Australia | Tertiary hospital |
204 9 months |
80.5 | 34.8 | One or more FRIDs | Edmonton Frail Scale (> 8 deficit points) |
Falls Functional decline Hospitalisation Institutionalisation |
| Cao et al. [36] | Cross-sectional | 2007 | USA | Community | 932 | 78 | 0 | DBI | (Difficulty in 2 or more functional domains out of a possible 8, e.g. gait speed, chair stands, grip strength, mobility, balance) |
Cognitive function ADL Chair stands Balance Gait speed Mobility Upper extremity function Hand grip strength |
| Cossette et al. [37] | Retrospective cohort | 2017 | Canada | Community |
1793 3 years |
74.4 | 48 | ACB score | Fried (fit = no components, pre-frail = 1 or 2 components, frail = 3+ components) |
PCS MCS |
| Gnjidic et al. [38] | Cross-sectional | 2012 | Finland | Community | 700 | 81.3 | 30.6 | DBI |
Gait speed (not defined) Chair stands test (not defined) TUGT (not defined) Grip strength (not defined) |
Gait speed Chair stands test Hand grip strength IADL score Barthel Index TUG test |
| Gnjidic et al. [39] | Cross-sectional | 2012 | Australia | Self-care retirement villages | 115 | 82.3 | 27 | DBI | Grip strength (f < 20 kg, m < 30 kg) |
SPPB score Grip strength |
| Hanlon et al. [40] | Prospective cohort | 2006 | USA | Outpatients |
808 1 year |
Not given (46.4% aged > 75 years) | 98 | Exposed to at least one anticholinergic drug/drug group (e.g. ‘anticholinergics’, ‘opioids’, ‘tricyclic antidepressants’) | (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 last 3 months, prolonged bed rest, or incontinence) |
ADRs Preventable ADRs |
| Jamsen et al. [41] | Prospective cohort | 2016 | Australia | Community |
1705 5 years |
76 | 100 | DBI | Fried (fit = no components, pre-frail = 1–2 components, frail = 3+ components) |
Transitions between frailty states, and death Pre-frail—fit Pre-frail—frail Pre-frail—death Frail—pre-frail Frail—death |
| Landi et al. [42] | Cross-sectional | 2007 | Italy | Community | 364 | 85.8 | 33 | Drugs that demonstrate serum anticholinergic activity in literature |
Gait speed (not defined) Grip strength (not defined) |
Gait speed SPPB Grip strength ADL score IADL score |
| Martinot et al. [43] | Prospective cohort | 2018 | France | Community |
12,405 3 years |
Not given (67.7% aged > 65 years) |
74 |
Exposed to at least 1 PIM using Laroche list (anticholinergics reported as, e.g., ‘tricyclic antidepressants’, ‘antipsychotics’, ‘long-acting benzodiazepines’) |
Strawbridge questionnaire (difficulty in 2 or more domains) | Changes in frailty status (frailty to fit state) |
| Porter et al. [44] | Retrospective cohort | 2019 | UK | Community |
1154 Up to 8 years lookback |
78.8 | 37.9 |
At least 1 PIM (anticholinergics identified using ACB scale and reported as, e.g., ‘tricyclic antidepressants’, ‘antipsychotics’, ‘benzodiazepines’) |
Fried (fit = no components, pre-frail = 1–2 component, frail = 3+ components) | Mortality |
| Sato et al. [45] | Cross-sectional and retrospective cohort | 2017 | Japan | Community | 306 (cross-sectional) | [87] | 44.4 | DBI |
Grip strength (not defined) TUGT (not defined) |
ADL score IADL score MMSE PGC Grip strength One-leg balance Repetition standing TUGT |
|
176 (cohort) 3 years |
[90] | 46.6 | ||||||||
| Wilson et al. [46] | Retrospective cohort | 2011 | Australia | RACFs |
602 1 year |
85.7 | 29.1 | DBI |
Gait speed** (not defined) Grip strength** (not defined) |
Falls |
| Zia et al. [47] | Case–control | 2016 | Malaysia | Community |
428 1 year |
75.3 (fallers) | 31.9% | ACB |
TUGT (≥ 13.5 s) Grip strength (f < 20 kg, m < 30 kg) |
Falls |
| 72.1 (non-fallers) | 33.3% |
ACB Anticholinergic Cognitive Burden scale, ADL Activities of Daily Living, ADR adverse drug reaction, DBI Drug Burden Index, f female, FRID fall-risk–increasing drug, IADL Instrumental Activities of Daily Living, m male, MCS Mental Component Summary, MMSE Mini-Mental State Examination, PCS Physical Component Summary, PGC Philadelphia Geriatric Center Morale Scale, PIM potentially inappropriate medicine, RACF residential aged care facility, SPPB Short Physical Performance Battery, TUGT timed up and go test
**Gait speed and grip strength were reported in a different study conducted by the first author, however, using the exact same cohort