1 ADAS‐Cog mean changes in score from baseline at 6 months or later (ITT‐LOCF) Show forest plot

10

4236

Mean Difference (IV, Fixed, 95% CI)

‐2.37 [‐2.73, ‐2.02]

2 MMSE mean change in score from baseline at 6 months or later (ITT‐LOCF) Show forest plot

9

3118

Mean Difference (IV, Fixed, 95% CI)

1.37 [1.13, 1.61]

3 Activities of daily living (DAD) mean changes in score from baseline at 6 months or later (ITT‐LOCF) Show forest plot

2

669

Mean Difference (IV, Fixed, 95% CI)

4.39 [1.96, 6.81]

4 Activities of daily living (PDS) mean change in score from baseline at 6 months (ITT) Show forest plot

5

2188

Mean Difference (IV, Fixed, 95% CI)

2.46 [1.55, 3.37]

5 Behavioural disturbance (NPI) mean changes from score from baseline at 6 months (ITT) Show forest plot

3

1005

Mean Difference (IV, Fixed, 95% CI)

‐2.44 [‐4.12, ‐0.76]

6 Global assessment with carer input (CIBIC‐Plus) (numbers improved or unchanged) at 6 months (ITT) Show forest plot

3

1306

Odds Ratio (M‐H, Fixed, 95% CI)

1.84 [1.47, 2.30]

7 Global assessment with carer input (CIBIC‐Plus) (numbers improved) at 6 months (ITT) Show forest plot

8

3402

Odds Ratio (M‐H, Fixed, 95% CI)

1.56 [1.32, 1.85]

8 GBS‐global assessment mean change in score from baseline at 52 weeks (ITT) Show forest plot

1

282

Mean Difference (IV, Fixed, 95% CI)

‐3.26 [‐7.38, 0.86]

9 Time spent by carer assisting in IADL and PSMS (mean changes in score from baseline min/day) at 6 months (ITT) Show forest plot

1

221

Mean Difference (IV, Fixed, 95% CI)

‐52.4 [‐118.78, 13.98]

10 Total number of withdrawals before end of treatment at 6 months or later (ITT) Show forest plot

13

5143

Odds Ratio (M‐H, Fixed, 95% CI)

1.76 [1.54, 2.02]

11 Total number of withdrawals due to an adverse event before end of treatment at 6 months or later (ITT) Show forest plot

13

5143

Odds Ratio (M‐H, Fixed, 95% CI)

2.32 [1.95, 2.76]

12 Number who suffered at least one adverse event before end of treatment at 6 months or later Show forest plot

12

4824

Odds Ratio (M‐H, Fixed, 95% CI)

2.51 [2.14, 2.95]

13 Number who suffered at least one adverse event of abdominal pain before end of treatment at 6 months or later Show forest plot

7

2704

Odds Ratio (M‐H, Fixed, 95% CI)

1.95 [1.46, 2.61]

14 Number who suffered at least one adverse event of abnormal gait before end of treatment at 6 months or later Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.60 [0.63, 4.09]

15 Number who suffered at least one adverse event of abnormal dreams before end of treatment at 6 months or later Show forest plot

1

153

Peto Odds Ratio (Peto, Fixed, 95% CI)

5.38 [1.34, 21.55]

16 Number who suffered at least one adverse event of accidental injury before end of treatment at 6 monthsorlater Show forest plot

3

651

Odds Ratio (M‐H, Fixed, 95% CI)

1.35 [0.86, 2.10]

17 Number who suffered at least one adverse event of agitation before end of treatment at 6 months or later Show forest plot

2

767

Odds Ratio (M‐H, Fixed, 95% CI)

0.95 [0.57, 1.56]

18 Number who suffered at least one adverse event of anorexia before end of treatment at 6 months or later Show forest plot

10

4419

Odds Ratio (M‐H, Fixed, 95% CI)

3.75 [2.89, 4.87]

19 Number who suffered at least one adverse event of anxiety before end of treatment at 6 months or later Show forest plot

1

286

Odds Ratio (M‐H, Fixed, 95% CI)

2.01 [0.82, 4.90]

20 Number who suffered at least one adverse event of arthralgia before end of treatment at 6 months or later Show forest plot

2

498

Odds Ratio (M‐H, Fixed, 95% CI)

1.22 [0.62, 2.40]

21 Number who suffered at least one adverse event of asthenia before end of treatment at 6 months or later Show forest plot

3

729

Odds Ratio (M‐H, Fixed, 95% CI)

2.47 [1.27, 4.81]

22 Number who suffered at least one adverse event of back pain before end of treatment at 6 months or later Show forest plot

1

290

Odds Ratio (M‐H, Fixed, 95% CI)

1.64 [0.62, 4.36]

23 Number who suffered at least one adverse event of confusion before end of treatment at 6 months or later Show forest plot

4

1331

Odds Ratio (M‐H, Fixed, 95% CI)

0.83 [0.52, 1.32]

24 Number who suffered at least one adverse event of conjunctivitis before end of treatment at 6 months or later Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.97 [0.70, 5.55]

25 Number who suffered at least one adverse event of constipation before end of treatment at 6 months or later Show forest plot

1

286

Odds Ratio (M‐H, Fixed, 95% CI)

0.66 [0.23, 1.91]

26 Number who suffered at least one adverse event of depression before end of treatment at 6 months or later Show forest plot

2

576

Odds Ratio (M‐H, Fixed, 95% CI)

1.58 [0.82, 3.04]

27 Number who suffered at least one adverse event of diarrhoea before end of treatment at 6 months or later Show forest plot

13

5173

Odds Ratio (M‐H, Fixed, 95% CI)

1.91 [1.59, 2.30]

28 Number who suffered at least one adverse event of dizziness before end of treatment at 6 months or later Show forest plot

12

4583

Odds Ratio (M‐H, Fixed, 95% CI)

1.99 [1.64, 2.42]

29 Number who suffered at least one adverse event of ecchymosis before end of treatment at 6 months or later Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.58 [0.54, 4.61]

30 Number who suffered at least one adverse event of fatigue before end of treatment at 6 months or later Show forest plot

1

319

Odds Ratio (M‐H, Fixed, 95% CI)

4.39 [1.21, 15.85]

31 Number who suffered at least one adverse event of fever before end of treatment at 6 months or later Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

0.87 [0.39, 1.93]

32 Number who suffered at least one adverse event of fracture before end of treatment at 6 months or later Show forest plot

5

2269

Odds Ratio (M‐H, Fixed, 95% CI)

0.96 [0.53, 1.74]

33 Number who suffered at least one adverse event of haemorrhage before end of treatment at 6 months or later Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.02 [0.35, 3.02]

34 Number who suffered at least one adverse event of headache before end of treatment at 6 months or later Show forest plot

9

3686

Odds Ratio (M‐H, Fixed, 95% CI)

1.56 [1.27, 1.91]

35 Number who suffered at least one adverse event of hostility before end of treatment at 6 months or later Show forest plot

2

576

Odds Ratio (M‐H, Fixed, 95% CI)

0.96 [0.49, 1.87]

36 Number who suffered at least one adverse event of increased cough before end of treatment at 6 months or later Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.19 [0.56, 2.52]

37 Number who suffered at least one adverse event of infection before end of treatment at 6 months or later Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.10 [0.51, 2.37]

38 Number who suffered at least one adverse event of insomnia before end of treatment at 6 months or later Show forest plot

7

2906

Odds Ratio (M‐H, Fixed, 95% CI)

1.49 [1.12, 2.00]

39 Number who suffered at least one adverse event of muscle cramp before end of treatment at 6 months or later Show forest plot

1

319

Odds Ratio (M‐H, Fixed, 95% CI)

13.32 [1.71, 103.74]

40 Number who suffered at least one adverse event of myasthenia before end of treatment at 6 months or later Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

2.10 [0.51, 8.64]

41 Number who suffered at least one adverse event of nausea before end of treatment at 6 months or later Show forest plot

13

5089

Odds Ratio (M‐H, Fixed, 95% CI)

4.87 [4.13, 5.74]

42 Number who suffered at least one adverse event of pain before end of treatment at 6 months or later Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

0.91 [0.47, 1.78]

43 Number who suffered at least one adverse event of peripheral oedema before end of treatment at 6 monthsorlater Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

2.08 [1.01, 4.28]

44 Number who suffered at least one adverse event of a rash before end of treatment at 6 months or later Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

0.72 [0.37, 1.42]

45 Number who suffered at least one adverse event of a respiratory tract infection before end of treatment at 6 m Show forest plot

1

290

Odds Ratio (M‐H, Fixed, 95% CI)

1.02 [0.49, 2.12]

46 Number who suffered at least one adverse event of rhinitis before end of treatment at 6 months or later Show forest plot

2

527

Odds Ratio (M‐H, Fixed, 95% CI)

1.38 [0.74, 2.58]

47 Number who suffered at least one adverse event of skin ulcer before end of treatment at 6 months or later Show forest plot

1

208

Odds Ratio (M‐H, Fixed, 95% CI)

1.51 [0.55, 4.12]

48 Number who suffered at least one adverse event of syncope before end of treatment at 6 months or later Show forest plot

5

2206

Odds Ratio (M‐H, Fixed, 95% CI)

1.90 [1.09, 3.33]

49 Number who suffered at least one adverse event of tremor before end of treatment at 6 months or later Show forest plot

2

633

Odds Ratio (M‐H, Fixed, 95% CI)

6.82 [1.99, 23.37]

50 Number who suffered at least one adverse event of urinary tract infection before end of treatment at 6 month Show forest plot

3

784

Odds Ratio (M‐H, Fixed, 95% CI)

0.90 [0.54, 1.48]

51 Number who suffered at least one adverse event of vertigo before end of treatment at 6 months or later Show forest plot

1

286

Odds Ratio (M‐H, Fixed, 95% CI)

3.95 [1.08, 14.46]

52 Number who suffered at least one adverse event of vomiting before end of treatment at 6 months or later Show forest plot

11

4703

Odds Ratio (M‐H, Fixed, 95% CI)

4.82 [3.91, 5.94]

53 Number who suffered at least one adverse event of weight loss before end of treatment at 6 months or later Show forest plot

4

1358

Odds Ratio (M‐H, Fixed, 95% CI)

2.99 [1.89, 4.75]

1 MMSE mean change from baseline (ITT‐LOCF) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 At 24 months

1

955

Mean Difference (IV, Fixed, 95% CI)

‐0.5 [‐1.33, 0.33]

2 Activities of daily living (ADCS‐ADL) (ITT‐LOCF) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 At 24 months

1

929

Mean Difference (IV, Fixed, 95% CI)

‐2.08 [‐4.58, 0.42]

3 Behavioural disturbance (NPI‐10) (ITT‐LOCF) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 At 24 months

1

955

Mean Difference (IV, Fixed, 95% CI)

0.54 [‐1.68, 2.76]

4 Cognitive function (SIB) (ITT‐LOCF) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

4.1 At 24 months

1

954

Mean Difference (IV, Fixed, 95% CI)

‐0.61 [‐3.66, 2.44]

5 Global Deterioration Scale (GDS) (ITT‐LOCF) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

5.1 At 24 months

1

954

Mean Difference (IV, Fixed, 95% CI)

0.11 [‐0.00, 0.22]

6 Total number of patients who withdrew before end of treatment Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 At 104 weeks

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

0.64 [0.50, 0.83]

7 Total number of patients who withdrew before end of treatment due to an adverse event Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 At 104 weeks

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

0.47 [0.32, 0.68]

8 Total number of patients who suffered an adverse event of nausea Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

0.37 [0.27, 0.50]

8.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

0.38 [0.23, 0.63]

9 Total number of patients who suffered an adverse event of vomiting Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

0.16 [0.10, 0.24]

9.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

0.25 [0.15, 0.43]

10 Total number of patients who suffered an adverse event of agitation Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

1.46 [0.93, 2.30]

10.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

1.26 [0.79, 2.00]

11 Total number of patients who suffered an adverse event of anorexia Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

11.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

0.42 [0.24, 0.72]

11.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

0.46 [0.24, 0.90]

12 Total number of patients who suffered an adverse event of diarrhoea Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

0.81 [0.50, 1.30]

12.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

1.03 [0.60, 1.77]

13 Total number of patients who suffered an adverse event of weight loss Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

0.28 [0.13, 0.61]

13.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

1.07 [0.67, 1.71]

14 Total number of patients who suffered an adverse event of headache Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

14.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

0.84 [0.47, 1.48]

14.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

0.82 [0.37, 1.81]

15 Total number of patients who suffered an adverse event of a fall Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

15.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

0.38 [0.18, 0.81]

15.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

1.21 [0.75, 1.94]

16 Total number of patients who suffered an adverse event of hypertension Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

16.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

0.34 [0.14, 0.81]

16.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

0.75 [0.40, 1.44]

17 Total number of patients who suffered an adverse event of depression Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

17.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

0.51 [0.24, 1.11]

17.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

0.67 [0.34, 1.30]

18 Total number of patients who suffered an adverse event of a urinary tract infection Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

18.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

1.63 [0.67, 3.96]

18.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

1.31 [0.70, 2.42]

19 Total number of patients who suffered an adverse event of aggression Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

19.1 By 16 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

1.57 [0.60, 4.09]

19.2 Between 16 and 104 weeks of treatment

1

857

Odds Ratio (M‐H, Fixed, 95% CI)

1.18 [0.64, 2.18]

20 Total number of patients who suffered a serious adverse event Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

20.1 At 104 weeks of treatment

1

994

Odds Ratio (M‐H, Fixed, 95% CI)

1.03 [0.79, 1.35]

21 Total number of patients who died before end of treatment Show forest plot

1

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

21.1 At 104 weeks

1

994

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.32 [0.78, 2.22]