Table 4.
Characteristics of selected RCTs for prevention of dementia/Alzheimer’s disease (AD) and other disorders
| Dementia/AD-related RCTs | RCTs for other disorders | ||
|---|---|---|---|
| Prevention of dementia with antihypertensive drugs in subjects with no history of cerebrovascular diseases | Prevention of coronary heart disease with lipid-lowering drugs | ||
| 4 RCTs in which cognitive measures were secondary endpoints [87, 88]; 15,427 participants |
Follow-up: from 2 to 5 years (median 2.9 years); incident cases (treatment/control): 236/259 HR (95% CI): 0.89 (0.74–1.07) |
4 RCTs [95]; 21,087 participants |
Follow-up: from 5 to 7 years Incident cases (treatment/control): 441/615 OR (95% CI): 0.70 (0.62–0.79) |
| Prevention of dementia and MCI with oestrogen alone or oestrogen plus progestin in postmenopausal women | Prevention of cardiovascular and cerebrovascular events with statins in diabetic subjects | ||
| 1 RCT, ancillary to a larger trial; early termination of treatment because overall health risk [60]; 7471 participants |
Follow-up: mean 4.4 years (maximum 7 years); incident cases (dementia or MCI: treatment/control):178/132 HR (95% CI) for dementia or MCI: 1.41 (1.12–1.76) |
4 RCTs [96]; 10,187 participants |
Follow-up: from 3 to 5 years (mean 3.8 years) Incident cases (treatment/control): 434/576 RR (95% CI): 0.75 (0.67–0.85) |
| Prevention of dementia/AD with naproxen or celecoxib in subjects with normal cognition and family history of AD | Prevention of cardiovascular and non-cardiovascular outcomes with aspirin | ||
| 1 RCT, early termination of treatment because overall health risk [89, 90]; 2528 participants (1537 for follow-up study) |
Follow-up: median 2 years (maximum 3.7 years) + 2-year extended follow-up after treatment cessation Incident cases of AD (treatment/control): 20/5; incident cases of dementia (treatment/control): 23/7; HR (95% CI) for AD with naproxen: 3.57 (1.09–11.7) HR (95% CI) for dementia with naproxen: 2.83 (1.04–7.72) HR (95% CI) for AD with celecoxib: 4.11 (1.30–13.0) HR (95% CI) for dementia with celecoxib: 3.04 (1.13–8.17). Incident cases of AD in follow-up study (treatment/control): 91/70; incident cases of dementia in follow-up study (treatment/control): 102/79; HR (95% CI) for AD with naproxen: 0.92 (0.62–1.35) HR (95% CI) for dementia with naproxen: 0.94 (0.65–1.35) HR (95% CI) for AD with celecoxib: 1.03 (0.72–1.50) HR (95% CI) for dementia with celecoxib: 1.03 (0.72–1.46) |
4 RCTs [97]; 102,621 participants |
Follow-up: from 3.6 to 10.1 years (mean 6 years) Incident cases of total cardiovascular events (treatment/control): 2107/2171 Incident cases of non-cardiovascular mortality (treatment/control): 1276/1311 OR (95% CI) for cardiovascular events: 0.90 (0.85–0.96) OR (95% CI) for non-cardiovascular mortality: 0.92 (0.85–1.00) |
| Prevention of dementia with simvastatin | Prevention of cardiovascular disease with vitamin and antioxidant supplementation | ||
| 1 RCT [91, 92]; 20,536 participants |
Follow-up: mean 5 years Incident cases (treatment/control): 31/31 OR (95% CI): 1.00 (0.61–1.65) |
50 RCTs: 30 primary and 20 secondary prevention RCTs [98]; 294,478 participants |
Follow-up: from 6 months to 12 years Incident cases (treatment/control): 16,571/14,691 RR (95% CI): 1.00 (0.98–1.02) |
| Prevention of dementia/AD with ginkgo biloba in subjects with normal cognition or MCI | Prevention of breast cancer with selective oestrogen receptor modulators | ||
| 1 RCT ancillary to a larger trial [93]; 3069 participants |
Follow-up: median 6.1 years (maximum 7.3 years) Incident cases of AD (treatment/control): 220/257; incident cases of dementia (treatment/control): 246/277 HR (95% CI) for AD: 1.16 (0.97–1.39) HR (95% CI) for dementia: 1.12 (0.94–1.33) |
9 RCTs [99]; 83,399 participants (306,617 women-years of follow-up) |
Follow-up: from 4 to 8 years (median 5.5 years) Incident cases (treatment/control): 945/1323 HR (95% CI): 0.62 (0.56–0.69) |
| Prevention of AD with ginkgo biloba in subjects with memory complaints [57] | Prevention of cancer with beta-carotene (alone or in combination with other antioxidants) supplementation | ||
| 1 RCT [57]; 2820 participants |
Follow-up: median 5 years Incident cases (treatment/control): 61/73 HR (95% CI): 0.84 (0.60–1.18) |
8 RCTs [100]; 180,702 participants |
Follow-up: from 4.0 to 12.9 years Incident cases (treatment + control): 10,600 RR (95% CI): 1.01 (0.98–1.04) |
| Prevention of dementia with α-tocopherol and selenium (alone or in combination) in men | Prevention of cancer with selenium supplementation | ||
| 1 RCT, ancillary to a larger trial; early termination of treatment due to a futility analysis (prostate cancer outcome), but follow-up is still ongoing [94]; 7547 participants (4246 for the extended follow-up) |
Follow-up: ongoing Incident cases after 8 years (treatment + control): 103 |
9 RCTs: 7 primary and 2 secondary prevention RCTs [101]; 152,538 participants |
Follow-up: from 2 to 10 years Incident cases (treatment/control): 1879/1959 RR (95% CI): 0.76 (0.58–0.99) |
| Prevention of hip fractures with vitamin D supplementation | |||
| 7 RCTs [102]; 9820 participants |
Follow-up: from 1 to 5 years Incident cases (treatment/control): 293/320 RR (95% CI) for vitamin D 700–800 IU/day: 0.73 (0.61–0.88) RR (95% CI) for vitamin D 400 IU/day: 1.15 (0.88–1.50) |
||
AD, Alzheimer’s disease; CI, confidence interval; HR, hazard ratio; IU, international unit; MCI, mild cognitive impairment; OR, odds ratio; RCT, randomized controlled trial; RR, relative risk.
Except for antihypertensive agents, data for dementia/AD are from individual RCTs, whereas data from trials in other conditions are from meta-analyses; this highlights the lack of RCTs for AD prevention.