Table 2.
Baseline characteristics describing the population of the included studies
| No. patients in each group | Age (years) | Sex (n) | Comorbidites and medical conditions | Medications | BMI | Smoking/alchol | Duration of Alzheimer disease | History of falls | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AChEIs users | Non-users | |||||||||||||||||||
| ID | AChEIs users | Non-users | AChEIs users | Non-users | Female | Male | Female | Male | AChEIs users | Non-users | AChEIs users | Non-users | AChEIs users | Non-users | AChEIs users | Non-users | AChEIs users | Non-users | AChEIs users | Non-users |
| Won et al. 202029 | 2385 | 7085 | 77 | 77 | 1719 | 666 | 5104 | 1981 | CVD 987 CKD 35 COPD 401 DM 539 Hyperlipidemia 142 Hypertension 1224 |
CVD 2969 CKDe 161 COPD 940 DM 1421 Hyperlipidemia 226 Hypertension 1224 |
TCA 299 SSRIs 313 Benzodiazepines 1225 Opioids 1176 Corticosteroids 739 Statins 423 Memantine 257 |
TCA 672 SSRIs 679 Benzodiazepines 3040 Opioids 2083 Corticosteroids 1574 Statins 832 Memantine 147 |
NA | NA | 233 | 391 | NA | NA | NA | NA |
| Ogunwale et al. 202031 | 152 274 | 207 741 | 75.8 (6.1) | 75.4 (6.5) | NA | NA | NA | NA | Rheumatoid arthritis (%) 0.5 Malabsorption (%) 0.4 Chronic lung disease (%) 26.1 Chronic liver disease (%) 6.8 Stage 3–4 kidney disease (%) 1.0 Congestive heart failure (%) 16.9 1 Hyperthyroidism (%) 0.9 Diabetes (%) 32.9 Parkinson’s disease (%) 7.1 Osteoarthritis (%) 33.2 Stroke (%) 1.2 |
Rheumatoid arthritis (%) 0.6 Malabsorption (%) 0.6 Chronic lung disease (%) 35.9 Chronic liver disease (%) 11.2 Stage 3–4 kidney disease (%) 1.9 Congestive heart failure (%) 24.9 Hyperthyroidism (%) 1.8 Diabetes (%) 37.2 Parkinson’s disease (%) 5.4 Osteoarthritis (%) 38.9 Stroke (%) 2.2 |
Glucocorticoid (%) 1.2 Androgen deprivation therapy (%) 0.0 Antiepileptic drugs (%) 9.8 Proton pump inhibitors (%) 40.7 SSRIs (%) 12.6 Others (%) 10.3 Opiates (%) 2.5 Any psychoactive medication (%) 27.5 |
Glucocorticoid (%) 1.7 Androgen deprivation therapy (%) 0.0 Antiepileptic drugs (%) 13.3 Proton pump inhibitors (%) 40.4 SSRIs (%) 9.7 Others (%) 8.9 Opiates (%) 2.0 Any psychoactive medication (%) 15.3 |
27.5 (4.4) | 28.0 (4.8) | Smoking 16.6 Chronic alcohol use (%) 19.0 |
Smoking 20.7 Chronic alcohol use (%) 20.0 |
NA | NA | NA | NA |
| Niznik 2019 | 93 760 | 15 480 | NA | NA | 71 978 (76.8) | 21 781 (23.2) | 12 223 (79.0) | 3257 (21.0) | Cancer 3,798 (4.1) Heart failure 4451 (15.4) End Stage Renal Disease 18 532 (9.1) Short of breath 5969 (6.4) Poor appetite 11,739 (12.5) Weight loss 5297 (5.7) Swallowing difficulty 3081 (3.3) Mechanically altered diet 49 631 (52.9) IV/parenteral nutrition or feeding tube 2510 (2.7) |
Cancer 664 (4.3) Heart failure 2246 (14.5) End Stage Renal Disease 1428 (9.2) Short of breath 953 (6.2) Poor appetite 2751 (17.8) Weight loss 1655 (10.7) Swallowing difficulty 709 (4.6) Mechanically altered diet 6710 (43.4) IV/parenteral nutrition or feeding tube 451 (2.9) |
Memantine 39 928 (42.6) Benzodiazepine 13 013 (13.9) Antipsychotic use 54 476 (22.6) Antidepressant use 53 096 (56.6) Highly Anticholinergic Drugs (Beers) 13 153 (14.0) |
Memantine 4414 (28.5) Benzodiazepine 1833 (11.8) Antipsychotic use 2,853 (18.4) Antidepressant use 7736 (50.0) Highly Anticholinergic Drugs (Beers) 1623 (10.5) |
NA | NA | NA | NA | NA | NA | NA | NA |
| Tamimi et al. 201824 | 1190 | 4760 | 75 | 75 | 76.4 | 23.6 | 76.4 | 23.6 | COPD 17.9 DM 7.8 Cardiac arrhythmia 7.7 Hemiplegia 0.3 Chronic liver disease 0.6 Ischaemic heart disease 2.9 Peptic ulcer 10.8 Renal diseases 2.6 |
COPD 17.8 DM 8.3 Cardiac arrhythmia 6.7 Hemiplegia 0.3 Chronic liver disease 0.5 Ischaemic heart disease 3.6 Peptic ulcer 10.8 Renal diseases 2.5 |
PPI 18.4 Statins 17.3 SSRI 18.9 Memantine 2.3 |
PPI 19.7 Statins 22.3 SSRI 15.7 Memantine 3.3 |
< 20: 18.0 20–24: 35.7 25–29: 20.3 ≥ 30: 6.2 Unknown: 19.8 |
< 20: 13.2 20–24: 35.6 25–29: 23.2 ≥ 30: 8.7 Unknown: 19.8 |
Current 10.7 Ex-smoker 24.5 |
Current 8.1 Ex-smoker 23.8 |
< 2: 29.4 2–6: 61.3 ≥ 6: 9.3 |
< 2: 29.4 2–6: 61.3 ≥ 6: 9.3 |
0.16±0.47 | 0.10±0.4 |
| Tamimi et al. 201723 | 223 | 309 | 84.0±7.0 | 84.6±6.4 | 78.5 | 21.5 | 73.8 | 26.2 | COPD 14.4 DM 9.4 CVD 9.9 Chronic liver disease 0.5 IHD 83.0 PU 5.4 Renal diseases 2.2 Known Osteoporosis 3.1 |
COPD 18.5 DM 6.5 CVD 13.9 Chronic liver disease 0.3 IHD 86.1 PU 10.0 Renal diseases 3.2 Known Osteoporosis 2.6 |
PPI 21.5 Statins 19.3 SSRI 25.6 Hypnotics 39.5 Diuretics 13.5 ACE inhibitors 17.5 Pre-baseline use of AChEIs 91.3 |
PPI 18.8 Statins 12.3 SSRI 20.4 Hypnotics 38.8 Diuretics 15.5 ACE inhibitors 10.4 Pre-baseline use of AChEIs 40.8 |
<20: 16.6 20–24: 29.2 25–29: 12.1 ≥30: 4.0 Unknown: 38.1 |
<20: 17.5 20–24: 33.0 25–29: 14.2 ≥30: 2.9 Unknown: 32.4 |
Current: 1.8 Ex-smoker: 4.9 |
Current: 1.9 Ex-smoker: 5.5 |
<2: 47.1 2-6: 46.6 ≥6: 6.3 |
<2: 35.9 2-6: 54.1 ≥6: 10.0 |
37.7 | 42.1 |
| Tamimi et al. 201232 | 1771 | 487 | 82.2±4.5 | 83.5±4.2 | 72 (70–74) | 25 (22–28) | 69 (65–73) | 27 (22–33) | NA | NA | SSRI 19 (17–21) | SSRI 26 (20–32) | 26.0±3.5 | 24.6±4.3 | 1 (0–1) | 1 (1–2) | NA | NA | NA | NA |
| Seitz et al. 201135 | 624 | 624 | 83.89 (6.02) | 83.96 (6.53) | 480 (76.92) | NA | 480 (76.92) | NA | Stroke 140 (22.44) 1 PD 39 (6.25) CHF 142 (22.76) Angina 152 (24.36) PrIor myocardial Infarction 180 (28.85) COPD 94 (15.06) Pneumonia 129 (20.67) CKD 52 (8.33) Diabetes 159 (25.48) Cancer 31 (4.97) |
Stroke 143 (22.92) PD 38 (6.09) CHF 138 (22.12) Angina 152 (24.36) PrIor myocardial Infarction 183 (29.33) COPD 98(15.71) Pneumonia 130(20.83) CKD 50 (8.01) Diabetes 159 (25.48) Cancer 27 (4.33) |
antidepressants 265 (42.47) antipsychotics 177 (28.37) Benzodiazepines 133 (21.31) |
antidepressants 248 (39.74) antipsychotics 169 (27.08) Benzodiazepines 140 (22.44) |
NA | NA | NA | NA | 3.23 (2.31) | 3.33 (2.61) | NA | NA |
| Gill et al. 200933 | 19 803 | 61 499 | 80.4 (6.3) | 80.4 (7.4) | NA | NA | NA | NA | CAD 8363 (42.2) PE 64 (0.3) Aortic valve stenosis 56 AF 4827 (24.4) Conduction disorder 1086 Seizure disorder 608 (3.1) Permanent pacemaker 314 (1.6) Implantable cardioverter defibrillator 15 (0.1) MI 1280 (6.5) CHF 1255 (6.3) PVD 440 (2.2) CVD 1729 (8.7) Chronic pulmonary disease 1341 (6.8) Connective tissue disease 198 (1.0) Ulcer disease 268 (1.4) Mild liver disease 19 (0.1) DM 1581 (8.0) DM with end-organ damage 177 (0.9) Hemiplegia or paraplegia 161 (0.8) Moderate or severe renal disease 415 (2.1) Primary cancer 819 (4.1) Moderate or severe liver disease 16 (0.1) Metastatic cancer 137 (0.7) |
CAD 28 916 (47.0) PE 273 (0.4) Aortic valve stenosis 236 (0.4) AF 17217 (28.0) Conduction disorder 4346 (7.1) Seizure disorder 3578 (5.8) Permanent pacemaker 1091 (1.8) Implantable cardioverter defibrillator 65 (0.1) MI 5670 (9.2) CHF 6921 (11.3) PVD 2212 (3.6) CVD 8706 (14.2) Chronic pulmonary disease 6882 (11.2) Connective tissue disease 906 (1.5) Ulcer disease 1332 (2.2) Mild liver disease 212 (0.3) DM 6782 (11.0) DM with end-organ damage 1123 (1.8) Hemiplegia or paraplegia 1295 (2.1) Moderate or severe renal disease 2529 (4.1) Primary cancer ) 3370 (5.5) Moderate or severe liver disease 222 (0.4) Metastatic cancer 864 (1.4) |
BB 4252 (21.5) NDHP CCB 1493 (7.5) Digoxin 1479 (7.5) Conventional antipsychotics 225 (1.1) Atypical antipsychotics 2352 (11.9) Antiarrhythmics 495 (2.5) Anticonvulsants 530 (2.7) Antidepressants 5177 (26.1) Antimanic agents 78 (0.4) Benzodiazepines 3624 (18.3) |
BB 13 693 (22.3) NDHP CCB 4675 (7.6) Digoxin 5610 (9.1) Conventional antipsychotics1117 (1.8) Atypical antipsychotics 6101 (9.9) Antiarrhythmics 1890 (3.1) Anticonvulsants 3022 (4.9) Antidepressants 14 850 (24.1) Antimanic agents 438 (0.7) Benzodiazepines 14 127 (23.0) |
NA | NA | NA | NA | NA | NA | NA | NA |
AchEI, acetylcholinesterase inhibitor; NA, not applicable.