Table 1 Descriptive characteristics of the study population.

Recruitment age, Median (Q1,Q3)

64 (62, 66)

64 (62, 66)

66 (64, 68)

<0.001

64 (62, 66)

66 (64, 68)

<0.001

64 (62, 66)

66 (64, 68)

<0.001

Sex, n (%)

<0.001

0.219

<0.001

Female

62641 (52)

61064 (53)

1547 (46)

61823 (52)

805 (51)

62297 (53)

344 (39)

Male

56778 (48)

54947 (47)

1797 (54)

56003 (48)

777 (49)

56244 (47)

534 (61)

Smoking status, n (%)

<0.001

0.099

<0.001

Never

59042 (50)

57505 (50)

1505 (45)

58290 (50)

747 (48)

58673 (50)

369 (42)

Previous

49923 (42)

48384 (42)

1511 (46)

49222 (42)

698 (45)

49512 (42)

411 (47)

Current

9757 (8)

9462 (8)

292 (9)

9638 (8)

118 (8)

9668 (8)

89 (10)

Alcohol_freq, n (%)

<0.001

<0.001

<0.001

Never

10115 (8)

9632 (8)

472 (14)

9904 (8)

211 (13)

9988 (8)

127 (14)

Special occasions only

14441 (12)

13947 (12)

485 (15)

14213 (12)

224 (14)

14322 (12)

119 (14)

One to three times a month

11932 (10)

11589 (10)

333 (10)

11781 (10)

149 (9)

11846 (10)

86 (10)

Once or twice a week

28784 (24)

28026 (24)

747 (22)

28379 (24)

400 (25)

28579 (24)

205 (23)

Three or four times a week

26405 (22)

25767 (22)

632 (19)

26109 (22)

296 (19)

26243 (22)

162 (18)

Daily or almost daily

27544 (23)

26864 (23)

664 (20)

27248 (23)

297 (19)

27366 (23)

178 (20)

Body mass index, Median (Q1,Q3)

27.02 (24.52, 29.99)

27.02 (24.52, 29.98)

27.18 (24.52, 30.39)

0.101

27.02 (24.52, 30)

26.94 (24.28, 29.86)

0.045

27.02 (24.51, 29.98)

27.8 (25.15, 31.24)

<0.001

Physical activity (IPAQ), n (%)

<0.001

0.445

<0.001

low

16221 (17)

15700 (17)

506 (20)

16024 (17)

196 (17)

16067 (17)

154 (23)

moderate

39043 (42)

38004 (42)

1025 (41)

38560 (42)

478 (40)

38788 (42)

255 (38)

high

38691 (41)

37706 (41)

971 (39)

38181 (41)

508 (43)

38434 (41)

257 (39)

Ethnicity, n (%)

<0.001

0.003

<0.001

British

110109 (93)

107014 (93)

3035 (91)

108656 (93)

1444 (92)

109312 (93)

797 (91)

White

129 (0)

120 (0)

9 (0)

122 (0)

6 (0)

127 (0)

2 (0)

Mixed

12 (0)

11 (0)

1 (0)

11 (0)

1 (0)

12 (0)

0 (0)

Asian or Asian British

5 (0)

5 (0)

0 (0)

5 (0)

0 (0)

5 (0)

0 (0)

Black or Black British

4 (0)

3 (0)

1 (0)

4 (0)

0 (0)

3 (0)

1 (0)

Chinese

145 (0)

145 (0)

0 (0)

145 (0)

0 (0)

145 (0)

0 (0)

Other ethnic group

500 (0)

489 (0)

11 (0)

496 (0)

4 (0)

496 (0)

4 (0)

Irish

2871 (2)

2754 (2)

116 (3)

2827 (2)

44 (3)

2834 (2)

37 (4)

Any other white background

2746 (2)

2685 (2)

61 (2)

2718 (2)

28 (2)

2729 (2)

17 (2)

White and Black Caribbean

47 (0)

43 (0)

4 (0)

45 (0)

2 (0)

46 (0)

1 (0)

White and Black African

41 (0)

41 (0)

0 (0)

41 (0)

0 (0)

41 (0)

0 (0)

White and Asian

91 (0)

90 (0)

1 (0)

91 (0)

0 (0)

90 (0)

1 (0)

Any other mixed background

127 (0)

123 (0)

4 (0)

123 (0)

4 (0)

127 (0)

0 (0)

Indian

854 (1)

830 (1)

24 (1)

845 (1)

9 (1)

850 (1)

4 (0)

Pakistani

178 (0)

173 (0)

5 (0)

175 (0)

3 (0)

178 (0)

0 (0)

Bangladeshi

14 (0)

14 (0)

0 (0)

14 (0)

0 (0)

14 (0)

0 (0)

Any other Asian background

220 (0)

214 (0)

6 (0)

216 (0)

4 (0)

220 (0)

0 (0)

Caribbean

502 (0)

469 (0)

33 (1)

483 (0)

19 (1)

497 (0)

5 (1)

African

288 (0)

278 (0)

10 (0)

284 (0)

4 (0)

281 (0)

7 (1)

Any other Black background

7 (0)

6 (0)

1 (0)

7 (0)

0 (0)

6 (0)

1 (0)

Volume hippocampus (Left), Median (Q1,Q3)

3762.9 (3520.5, 4034.07)

3763.9 (3522.98, 4034.65)

3476.8 (3283.5, 3704.9)

<0.001

3763.3 (3522.5, 4034.4)

3476.8 (3262.7, 3583.8)

<0.001

3763.3 (3521.2, 4034.3)

3476.8 (3425.3, 3654.2)

0.009

Volume hippocampus (Right), Median (Q1,Q3)

3927.25 (3666.62, 4205.65)

3928.15 (3668.85, 4205.98)

3568.7 (3328.65, 3860.2)

<0.001

3927.7 (3667.9, 4205.8)

3463.7 (3229.9, 3810.8)

<0.001

3927.6 (3667.2, 4205.8)

3657.6 (3337.2, 3796.5)

0.008

Volume entorhinal cortex (Right), Median (Q1,Q3)

1789 (1561, 2051)

1789.5 (1561, 2052)

1641 (1403, 1842)

0.005

1789 (1561, 2052)

1543 (1369, 1815)

0.061

1789 (1561, 2052)

1603 (1439, 1722)

0.019

Volume entorhinal cortex (Left), Median (Q1,Q3)

1911.5 (1661, 2186.75)

1912 (1661.25, 2187)

1685 (1493, 2078)

0.023

1912 (1661, 2187)

1836 (1478, 2067)

0.195

1912 (1661, 2187)

1634 (1488, 1834)

0.028

Headsize, Median (Q1,Q3)

1.28 (1.2, 1.37)

1.28 (1.2, 1.37)

1.31 (1.21, 1.39)

0.408

1.28 (1.2, 1.37)

1.32 (1.21, 1.38)

0.392

1.28 (1.2, 1.37)

1.33 (1.32, 1.4)

0.089

Fractional anisotropy cingulum parahippocampus (Right), Median (Q1,Q3)

0.46 (0.43, 0.48)

0.46 (0.43, 0.48)

0.45 (0.42, 0.46)

0.027

0.46 (0.43, 0.48)

0.42 (0.4, 0.44)

0.002

0.46 (0.43, 0.48)

0.48 (0.45, 0.48)

0.387

Fractional anisotropy cingulum parahippocampus (Left), Median (Q1,Q3)

0.46 (0.43, 0.48)

0.46 (0.43, 0.48)

0.44 (0.43, 0.47)

0.096

0.46 (0.43, 0.48)

0.42 (0.41, 0.44)

0.002

0.46 (0.43, 0.48)

0.47 (0.46, 0.47)

0.372

Mean diffusivity cingulum parahippocampus (Left), Median (Q1,Q3)

0 .000762(0.000738, 0.000787)

0 .000762(0.000738, 0.000787)

0.000781 (0.000741, 0.00082)

0.048

0.000762(0.000738,0.000787)

0.000816 (0.000784, 0.000844)

0.001

0.000762(0.000738, 0.000787)

0.000723 (0.000721, 0.000768)

0.13

Mean diffusivity cingulum parahippocampus (Right), Median (Q1,Q3)

0.000765(0.000742, 0.000789)

0.000765 (0.000742, 0.000787)

0 .000781(0.000746, 0.00082)

0.036

0.000765 (0.000742, 0.000789)

0.000814(0.000803, 0.000818)

<0.001

0.000765(0.000742, 0.000789)

0.000740 (0.000727, 0.000771)

0.247

Reaction time, Median (Q1,Q3)

567 (508, 645)

567 (508, 645)

597 (528, 687)

<0.001

567 (508, 645)

590 (527, 680)

<0.001

567 (508, 645)

613 (539, 695)

<0.001

Fluid intelligence, Median (Q1,Q3)

6 (4, 7)

6 (4, 7)

5 (4, 7)

<0.001

6 (4, 7)

5 (4, 6)

<0.001

6 (4, 7)

5 (3, 6)

<0.001

Handgrip strength (Left), Median (Q1,Q3)

26 (20, 36)

26 (20, 36)

26 (18, 34)

<0.001

26 (20, 36)

25 (18, 34)

<0.001

26 (20, 36)

28 (20, 36)

0.859

Handgrip strength (Right), Median (Q1,Q3)

28 (22, 38)

28 (22, 38)

28 (21, 37)

<0.001

28 (22, 38)

28 (20, 36)

<0.001

28 (22, 38)

30 (22, 38)

0.886

AD_time, Median (Q1,Q3)

4538 (4229, 4812)

4546 (4241, 4816)

4122 (3308.25, 4583)

<0.001

4544 (4237, 4815)

3621 (2838.5, 4167)

<0.001

4539 (4230, 4812)

4237 (3500.5, 4670)

<0.001

dementia_time, Median (Q1,Q3)

4531 (4224, 4810)

4546 (4242, 4816)

3608.5 (2854, 4196)

<0.001

4539 (4230, 4812)

3617 (2858, 4215.5)

<0.001

4537 (4228, 4812)

3491 (2749, 4128)

<0.001

VAD_time, Median (Q1,Q3)

4541 (4231, 4814)

4546 (4242, 4816)

4260 (3518, 4678)

<0.001

4543 (4235, 4814.5)

4355.5 (3741.75, 4726.25)

<0.001

4544 (4236, 4815)

3640.5 (2926.75, 4228.5)

<0.001

Fasting time (hrs), Median (Q1,Q3)

3 (3, 4)

3 (3, 4)

4 (3, 5)

<0.001

3 (3, 4)

4 (3, 5)

<0.001

3 (3, 4)

4 (3, 5)

<0.001

Medication use

Antidiabetics (A10), n (%)

<0.001

<0.001

<0.001

No

113349 (95)

110334 (95)

2964 (89)

111911 (95)

1425 (90)

112609 (95)

740 (84)

Yes

6070 (5)

5677 (5)

380 (11)

5915 (5)

157 (10)

5932 (5)

138 (16)

Antihypertensives (C02), n (%)

<0.001

0.047

<0.001

No

116582 (98)

113313 (98)

3207 (96)

115040 (98)

1532 (97)

115746 (98)

836 (95)

Yes

2837 (2)

2698 (2)

137 (4)

2786 (2)

50 (3)

2795 (2)

42 (5)

Diuretics (C03), n (%)

<0.001

0.156

<0.001

No

104407 (87)

101535 (88)

2820 (84)

103031 (87)

1364 (86)

103704 (87)

703 (80)

Yes

15012 (13)

14476 (12)

524 (16)

14795 (13)

218 (14)

14837 (13)

175 (20)

Beta blocking agents (C07), n (%)

<0.001

<0.001

<0.001

No

106139 (89)

103304 (89)

2780 (83)

104777 (89)

1355 (86)

105456 (89)

683 (78)

Yes

13280 (11)

12707 (11)

564 (17)

13049 (11)

227 (14)

13085 (11)

195 (22)

Calcium channel blockers (C08), n (%)

<0.001

0.002

<0.001

No

105519 (88)

102679 (89)

2790 (83)

104144 (88)

1358 (86)

104831 (88)

688 (78)

Yes

13900 (12)

13332 (11)

554 (17)

13682 (12)

224 (14)

13710 (12)

190 (22)

Renin-angiotensin system drugs (C09), n (%)

<0.001

<0.001

<0.001

No

94239 (79)

91844 (79)

2352 (70)

93053 (79)

1177 (74)

93700 (79)

539 (61)

Yes

25180 (21)

24167 (21)

992 (30)

24773 (21)

405 (26)

24841 (21)

339 (39)

Lipid lowering (C10), n (%)

<0.001

<0.001

<0.001

No

81670 (68)

79753 (69)

1886 (56)

80716 (69)

944 (60)

81258 (69)

412 (47)

Yes

37749 (32)

36258 (31)

1458 (44)

37110 (31)

638 (40)

37283 (31)

466 (53)

Opioids (N02A), n (%)

<0.001

<0.001

<0.001

No

111323 (93)

108324 (93)

2946 (88)

109901 (93)

1414 (89)

110564 (93)

759 (86)

Yes

8096 (7)

7687 (7)

398 (12)

7925 (7)

168 (11)

7977 (7)

119 (14)

Analgesics & antipyretics (N02B), n (%)

<0.001

<0.001

<0.001

No

77513 (65)

75708 (65)

1773 (53)

76612 (65)

891 (56)

77114 (65)

399 (45)

Yes

41906 (35)

40303 (35)

1571 (47)

41214 (35)

691 (44)

41427 (35)

479 (55)

Antimigraine (N02C), n (%)

0.074

0.104

0.911

No

118218 (99)

114833 (99)

3321 (99)

116634 (99)

1573 (99)

117348 (99)

870 (99)

Yes

1201 (1)

1178 (1)

23 (1)

1192 (1)

9 (1)

1193 (1)

8 (1)

Antiepileptics (N03A), n (%)

<0.001

<0.001

<0.001

No

117262 (98)

114005 (98)

3199 (96)

115727 (98)

1527 (97)

116437 (98)

825 (94)

Yes

2157 (2)

2006 (2)

145 (4)

2099 (2)

55 (3)

2104 (2)

53 (6)

Anticholinergics (N04A), n (%)

<0.001

0.025

0.454

No

119337 (100)

115940 (100)

3335 (100)

117747 (100)

1578 (100)

118460 (100)

877 (100)

Yes

82 (0)

71 (0)

9 (0)

79 (0)

4 (0)

81 (0)

1 (0)

Dopaminergic (N04B), n (%)

<0.001

<0.001

0.053

No

118965 (100)

115672 (100)

3235 (97)

117393 (100)

1561 (99)

118094 (100)

871 (99)

Yes

454 (0)

339 (0)

109 (3)

433 (0)

21 (1)

447 (0)

7 (1)

Antipsychotics (N05A), n (%)

<0.001

0.077

<0.001

No

118488 (99)

115138 (99)

3292 (98)

116913 (99)

1563 (99)

117626 (99)

862 (98)

Yes

931 (1)

873 (1)

52 (2)

913 (1)

19 (1)

915 (1)

16 (2)

Anxiolytics (N05B), n (%)

<0.001

0.005

0.122

No

118883 (100)

115508 (100)

3314 (99)

117304 (100)

1567 (99)

118012 (100)

871 (99)

Yes

536 (0)

503 (0)

30 (1)

522 (0)

15 (1)

529 (0)

7 (1)

Hypnotics & sedatives (N05C), n (%)

<0.001

0.181

0.003

No

118327 (99)

114978 (99)

3289 (98)

116754 (99)

1562 (99)

117466 (99)

861 (98)

Yes

1092 (1)

1033 (1)

55 (2)

1072 (1)

20 (1)

1075 (1)

17 (2)

Antidepressants (N06A), n (%)

<0.001

<0.001

<0.001

No

110795 (93)

107846 (93)

2902 (87)

109408 (93)

1381 (87)

110053 (93)

742 (85)

Yes

8624 (7)

8165 (7)

442 (13)

8418 (7)

201 (13)

8488 (7)

136 (15)

Psychostimulants (N06B), n (%)

0.574

1

1

No

119389 (100)

115982 (100)

3343 (100)

117796 (100)

1582 (100)

118511 (100)

878 (100)

Yes

30 (0)

29 (0)

1 (0)

30 (0)

0 (0)

30 (0)

0 (0)

Psycholeptics (N06C), n (%)

0.113

0.429

0.267

No

119377 (100)

115972 (100)

3341 (100)

117785 (100)

1581 (100)

118500 (100)

877 (100)

Yes

42 (0)

39 (0)

3 (0)

41 (0)

1 (0)

41 (0)

1 (0)

Anti dementia drugs (N06D), n (%)

<0.001

<0.001

0.08

No

118373 (99)

115034 (99)

3287 (98)

116826 (99)

1544 (98)

117508 (99)

865 (99)

Yes

1046 (1)

977 (1)

57 (2)

1000 (1)

38 (2)

1033 (1)

13 (1)

Parasympathomimetics (N07A), n (%)

0.138

0.612

1

No

119348 (100)

115944 (100)

3340 (100)

117756 (100)

1581 (100)

118470 (100)

878 (100)

Yes

71 (0)

67 (0)

4 (0)

70 (0)

1 (0)

71 (0)

0 (0)

Drugs for addictive disorders (N07B), n (%)

<0.001

0.005

0.006

No

119266 (100)

115872 (100)

3330 (100)

117679 (100)

1575 (100)

118393 (100)

873 (99)

Yes

153 (0)

139 (0)

14 (0)

147 (0)

7 (0)

148 (0)

5 (1)

Antivertigo preparations (N07C), n (%)

0.002

0.003

0.011

No

118752 (99)

115377 (99)

3312 (99)

117177 (99)

1564 (99)

117885 (99)

867 (99)

Yes

667 (1)

634 (1)

32 (1)

649 (1)

18 (1)

656 (1)

11 (1)

Anesthetics (N01A), n (%)

1

1

1

No

119366 (100)

115959 (100)

3343 (100)

117773 (100)

1582 (100)

118488 (100)

878 (100)

Yes

53 (0)

52 (0)

1 (0)

53 (0)

0 (0)

53 (0)

0 (0)

Proton pump inhibitors (A02BC), n (%)

<0.001

<0.001

<0.001

No

102449 (86)

99701 (86)

2702 (81)

101140 (86)

1298 (82)

101772 (86)

677 (77)

Yes

16970 (14)

16310 (14)

642 (19)

16686 (14)

284 (18)

16769 (14)

201 (23)

Digitalis glycosides (C01AA), n (%)

<0.001

0.057

<0.001

No

118864 (100)

115486 (100)

3314 (99)

117282 (100)

1569 (99)

118002 (100)

862 (98)

Yes

555 (0)

525 (0)

30 (1)

544 (0)

13 (1)

539 (0)

16 (2)

Platelet aggregation inhibitors (B01AC), n (%)

<0.001

<0.001

<0.001

No

92890 (78)

90617 (78)

2233 (67)

91769 (78)

1108 (70)

92395 (78)

495 (56)

Yes

26529 (22)

25394 (22)

1111 (33)

26057 (22)

474 (30)

26146 (22)

383 (44)