Background
Methods
Study design and participants
Assessment of obesity
Assessment of sarcopenia
Identification of sarcopenic obesity
Assessment of dementia
Assessment of brain structure
Assessment of mediators
Assessment of covariates
Statistical analysis
Results
Baseline characteristics
Women | Men | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Characteristic | Normal | Obesity | Sarcopenia | Sarcopenic obesity | P | Normal | Obesity | Sarcopenia | Sarcopenic obesity | P |
(n = 71532) | (n = 22241) | (n = 11830) | (n = 4837) | (n = 66948) | (n = 22328) | (n = 6475) | (n = 2676) | |||
Skeletal muscle mass index, mean (SD), kg/m2 | 3.37 (0.30) | 3.81 (0.38) | 3.29 (0.31) | 3.78 (0.41) | < 0.001 | 5.27 (0.37) | 5.77 (0.42) | 5.19 (0.40) | 5.73 (0.43) | < 0.001 |
Grip strength, mean (SD), kg | 22.98 (4.37) | 22.93 (4.52) | 12.25 (2.98) | 12.01 (3.09) | < 0.001 | 38.65 (6.65) | 38.72 (7.02) | 22.17 (4.07) | 21.75 (4.42) | < 0.001 |
Age, mean (SD), years | 63.89 (2.78) | 63.86 (2.79) | 64.45 (2.83) | 64.34 (2.82) | < 0.001 | 64.14 (2.80) | 64.04 (2.78) | 64.78 (2.85) | 64.66 (2.81) | < 0.001 |
Ethnicity, n (%) | < 0.001 | < 0.001 | ||||||||
White | 69990 (97.8) | 21440 (96.4) | 11276 (95.3) | 4570 (94.5) | 65258 (97.5) | 21862 (97.9) | 5886 (90.9) | 2529 (94.5) | ||
Asian or Asian British | 515 (0.7) | 171 (0.8) | 335 (2.8) | 128 (2.6) | 782 (1.2) | 150 (0.7) | 393 (6.1) | 82 (3.1) | ||
Black or Black British | 366 (0.5) | 405 (1.8) | 52 (0.4) | 77 (1.6) | 416 (0.6) | 148 (0.7) | 75 (1.2) | 33 (1.2) | ||
Other | 661 (0.9) | 225 (1.0) | 167 (1.4) | 62 (1.3) | 492 (0.7) | 168 (0.8) | 121 (1.9) | 32 (1.2) | ||
Education, n (%) | < 0.001 | < 0.001 | ||||||||
No degree | 17646 (24.7) | 7198 (32.4) | 3902 (33.0) | 2042 (42.2) | 15185 (22.7) | 7031 (31.5) | 2078 (32.1) | 1125 (42.0) | ||
Degree | 53886 (75.3) | 15043 (67.6) | 7928 (67.0) | 2795 (57.8) | 51763 (77.3) | 15297 (68.5) | 4397 (67.9) | 1551 (58.0) | ||
Townsend deprivation index, mean (SD) | − 1.81 (2.78) | − 1.14 (3.11) | − 1.37 (2.98) | − 0.49 (3.28) | < 0.001 | − 1.79 (2.86) | − 1.28 (3.09) | − 0.71 (3.35) | − 0.26 (3.41) | < 0.001 |
Physical activity level, n (%) | < 0.001 | < 0.001 | ||||||||
Low | 9244 (12.9) | 4802 (21.6) | 2039 (17.2) | 1394 (28.8) | 9683 (14.5) | 5175 (23.2) | 1364 (21.1) | 796 (29.7) | ||
Moderate | 31534 (44.1) | 10013 (45.0) | 5235 (44.3) | 2085 (43.1) | 26866 (40.1) | 8863 (39.7) | 2731 (42.2) | 1060 (39.6) | ||
High | 30754 (43.0) | 7426 (33.4) | 4556 (38.5) | 1358 (28.1) | 30399 (45.4) | 8290 (37.1) | 2380 (36.8) | 820 (30.6) | ||
Smoking status, n (%) | < 0.001 | < 0.001 | ||||||||
Never | 41364 (57.8) | 12174 (54.7) | 6981 (59.0) | 2721 (56.3) | 29872 (44.6) | 7596 (34.0) | 2854 (44.1) | 931 (34.8) | ||
Former | 25193 (35.2) | 8770 (39.4) | 3970 (33.6) | 1807 (37.4) | 30360 (45.3) | 12773 (57.2) | 2789 (43.1) | 1499 (56.0) | ||
Current | 4975 (7.0) | 1297 (5.8) | 879 (7.4) | 309 (6.4) | 6716 (10.0) | 1959 (8.8) | 832 (12.8) | 246 (9.2) | ||
Drinking status, n (%) | < 0.001 | < 0.001 | ||||||||
Never | 3942 (5.5) | 1810 (8.1) | 1056 (8.9) | 611 (12.6) | 1517 (2.3) | 539 (2.4) | 317 (4.9) | 119 (4.4) | ||
Former | 2306 (3.2) | 1080 (4.9) | 589 (5.0) | 380 (7.9) | 1986 (3.0) | 848 (3.8) | 392 (6.1) | 189 (7.1) | ||
Current | 65284 (91.3) | 19351 (87.0) | 10185 (86.1) | 3846 (79.5) | 63445 (94.8) | 20941 (93.8) | 5766 (89.1) | 2368 (88.5) | ||
Oily fish intake, n (%) | < 0.001 | < 0.001 | ||||||||
Never | 4807 (6.7) | 1872 (8.4) | 1149 (9.7) | 598 (12.4) | 5129 (7.7) | 2041 (9.1) | 819 (12.6) | 317 (11.8) | ||
Less than once a week | 18999 (26.6) | 6341 (28.5) | 3266 (27.6) | 1322 (27.3) | 20315 (30.3) | 7129 (31.9) | 1965 (30.3) | 838 (31.3) | ||
Once a week | 30849 (43.1) | 9102 (40.9) | 4925 (41.6) | 1918 (39.7) | 27040 (40.4) | 8666 (38.8) | 2399 (37.1) | 979 (36.6) | ||
More than twice a week | 16877 (23.6) | 4926 (22.1) | 2490 (21.0) | 999 (20.7) | 14464 (21.6) | 4492 (20.1) | 1292 (20.0) | 542 (20.3) | ||
Poultry intake, n (%) | < 0.001 | < 0.001 | ||||||||
Never | 3469 (4.8) | 702 (3.2) | 680 (5.7) | 193 (4.0) | 2192 (3.3) | 486 (2.2) | 350 (5.4) | 84 (3.1) | ||
Less than once a week | 8775 (12.3) | 2217 (10.0) | 1426 (12.1) | 508 (10.5) | 8892 (13.3) | 2732 (12.2) | 997 (15.4) | 389 (14.5) | ||
Once a week | 28342 (39.6) | 7994 (35.9) | 4682 (39.6) | 1781 (36.8) | 27909 (41.7) | 8793 (39.4) | 2668 (41.2) | 1057 (39.5) | ||
More than twice a week | 30946 (43.3) | 11328 (50.9) | 5042 (42.6) | 2355 (48.7) | 27955 (41.8) | 10317 (46.2) | 2460 (38.0) | 1146 (42.8) | ||
Processed meat intake, n (%) | < 0.001 | < 0.001 | ||||||||
Never | 9044 (12.6) | 1866 (8.4) | 1564 (13.2) | 468 (9.7) | 3455 (5.2) | 612 (2.7) | 500 (7.7) | 116 (4.3) | ||
Less than once a week | 29196 (40.8) | 7975 (35.9) | 4482 (37.9) | 1644 (34.0) | 16120 (24.1) | 4456 (20.0) | 1372 (21.2) | 526 (19.7) | ||
Once a week | 20202 (28.2) | 6897 (31.0) | 3484 (29.5) | 1509 (31.2) | 20882 (31.2) | 6859 (30.7) | 1943 (30.0) | 760 (28.4) | ||
More than twice a week | 13090 (18.3) | 5503 (24.7) | 2300 (19.4) | 1216 (25.1) | 26491 (39.6) | 10401 (46.6) | 2660 (41.1) | 1274 (47.6) | ||
Beef intake, n (%) | < 0.001 | < 0.001 | ||||||||
Never | 8662 (12.1) | 1947 (8.8) | 1630 (13.8) | 572 (11.8) | 4743 (7.1) | 935 (4.2) | 734 (11.3) | 207 (7.7) | ||
Less than once a week | 33892 (47.4) | 10151 (45.6) | 5565 (47.0) | 2192 (45.3) | 30735 (45.9) | 9000 (40.3) | 2837 (43.8) | 1021 (38.2) | ||
Once a week | 21203 (29.6) | 7272 (32.7) | 3458 (29.2) | 1551 (32.1) | 23278 (34.8) | 8723 (39.1) | 2126 (32.8) | 989 (37.0) | ||
More than twice a week | 7775 (10.9) | 2871 (12.9) | 1177 (9.9) | 522 (10.8) | 8192 (12.2) | 3670 (16.4) | 778 (12.0) | 459 (17.2) | ||
Pork intake, n (%) | < 0.001 | < 0.001 | ||||||||
Never | 12729 (17.8) | 3286 (14.8) | 2500 (21.1) | 853 (17.6) | 8249 (12.3) | 2173 (9.7) | 1177 (18.2) | 349 (13.0) | ||
Less than once a week | 41292 (57.7) | 12395 (55.7) | 6275 (53.0) | 2507 (51.8) | 39443 (58.9) | 12261 (54.9) | 3351 (51.8) | 1317 (49.2) | ||
Once a week | 15813 (22.1) | 5835 (26.2) | 2743 (23.2) | 1307 (27.0) | 16828 (25.1) | 6699 (30.0) | 1628 (25.1) | 837 (31.3) | ||
More than twice a week | 1698 (2.4) | 725 (3.3) | 312 (2.6) | 170 (3.5) | 2428 (3.6) | 1195 (5.4) | 319 (4.9) | 173 (6.5) | ||
Lamb intake, n (%) | < 0.001 | < 0.001 | ||||||||
Never | 12630 (17.7) | 3451 (15.5) | 2263 (19.1) | 814 (16.8) | 8668 (12.9) | 2528 (11.3) | 1066 (16.5) | 397 (14.8) | ||
Less than once a week | 40431 (56.5) | 12284 (55.2) | 6343 (53.6) | 2552 (52.8) | 37814 (56.5) | 11904 (53.3) | 3337 (51.5) | 1294 (48.4) | ||
Once a week | 16736 (23.4) | 5821 (26.2) | 2896 (24.5) | 1296 (26.8) | 18166 (27.1) | 6888 (30.8) | 1743 (26.9) | 835 (31.2) | ||
More than twice a week | 1735 (2.4) | 685 (3.1) | 328 (2.8) | 175 (3.6) | 2300 (3.4) | 1008 (4.5) | 329 (5.1) | 150 (5.6) | ||
Milk intake, n (%) | < 0.001 | < 0.001 | ||||||||
No | 2196 (3.1) | 745 (3.3) | 443 (3.7) | 196 (4.1) | 1909 (2.9) | 710 (3.2) | 241 (3.7) | 98 (3.7) | ||
Yes | 69336 (96.9) | 21496 (96.7) | 11387 (96.3) | 4641 (95.9) | 65039 (97.1) | 21618 (96.8) | 6234 (96.3) | 2578 (96.3) | ||
Coffee intake, mean (SD), cups | 1.97 (1.81) | 2.11 (1.98) | 1.85 (1.86) | 1.99 (2.15) | < 0.001 | 2.11 (1.97) | 2.24 (2.13) | 1.95 (2.05) | 2.06 (2.28) | < 0.001 |
Fresh fruit intake, n (%) | < 0.001 | < 0.001 | ||||||||
0–1 pieces/day | 17206 (24.1) | 5726 (25.7) | 3222 (27.2) | 1289 (26.6) | 27013 (40.3) | 8729 (39.1) | 2817 (43.5) | 1052 (39.3) | ||
2–3 pieces/day | 39561 (55.3) | 11955 (53.8) | 6230 (52.7) | 2515 (52.0) | 30876 (46.1) | 9879 (44.2) | 2794 (43.2) | 1135 (42.4) | ||
≥ 3 pieces/day | 14765 (20.6) | 4560 (20.5) | 2378 (20.1) | 1033 (21.4) | 9059 (13.5) | 3720 (16.7) | 864 (13.3) | 489 (18.3) | ||
Vegetable intake, mean (SD), tablespoons/day | 5.23 (3.05) | 5.19 (3.05) | 5.12 (3.24) | 5.18 (3.35) | 0.005 | 4.92 (3.28) | 4.98 (3.31) | 4.85 (4.04) | 4.98 (3.72) | 0.005 |
Cardiovascular disease, n (%) | < 0.001 | < 0.001 | ||||||||
No | 64815 (90.6) | 3758 (16.9) | 10130 (85.6) | 3610 (74.6) | 53363 (79.7) | 15321 (68.6) | 4653 (71.9) | 1574 (58.8) | ||
Yes | 6717 (9.4) | 18483 (83.1) | 1700 (14.4) | 1227 (25.4) | 13585 (20.3) | 7007 (31.4) | 1822 (28.1) | 1102 (41.2) | ||
Cerebrovascular disease, n (%) | < 0.001 | < 0.001 | ||||||||
No | 67009 (93.7) | 20436 (91.9) | 10671 (90.2) | 4247 (87.8) | 60282 (90.0) | 19327 (86.6) | 5385 (83.2) | 2124 (79.4) | ||
Yes | 4523 (6.3) | 1805 (8.1) | 1159 (9.8) | 590 (12.2) | 6666 (10.0) | 3001 (13.4) | 1090 (16.8) | 552 (20.6) | ||
Diabetes, n (%) | < 0.001 | < 0.001 | ||||||||
No | 67709 (94.7) | 17872 (80.4) | 10838 (91.6) | 3555 (73.5) | 59952 (89.6) | 15824 (70.9) | 5280 (81.5) | 1552 (58.0) | ||
Yes | 3823 (5.3) | 4369 (19.6) | 992 (8.4) | 1282 (26.5) | 6996 (10.4) | 6504 (29.1) | 1195 (18.5) | 1124 (42.0) | ||
Polygenic risk score, n (%) | 0.154 | 0.084 | ||||||||
Low | 34863 (48.7) | 10971 (49.3) | 5689 (48.1) | 2342 (48.4) | 32482 (48.5) | 11034 (49.4) | 3135 (48.4) | 1278 (47.8) | ||
High | 36669 (51.3) | 11270 (50.7) | 6141 (51.9) | 2495 (51.6) | 34466 (51.5) | 11294 (50.6) | 3340 (51.6) | 1398 (52.2) |
Associations of obesity, sarcopenia, and sarcopenic obesity with incident dementia risk
Women | Men | |||
---|---|---|---|---|
HR (95%CI) | AR% | HR (95%CI) | AR% | |
Unadjusted model | ||||
Normal | Ref | - | Ref | - |
Obesity | 0.993 (0.902–1.094) | NA | 1.130 (1.037–1.230) | 11.504% |
Sarcopenia # | 2.030 (1.689–2.440) | 50.739% | 2.695 (2.243–3.240) | 62.894% |
Sarcopenia § | 1.347 (1.184–1.533) | 25.760% | 1.766 (1.530–2.039) | 43.375% |
Sarcopenic obesity | 1.824 (1.578–2.107) | 45.175% | 2.649 (2.275–3.083) | 62.250% |
Age-adjusted model | ||||
Normal | Ref | - | Ref | - |
Obesity | 0.999 (0.907–1.100) | NA | 1.160 (1.065–1.263) | 13.793% |
Sarcopenia # | 1.807 (1.503–2.172) | 44.660% | 2.380 (1.980–2.861) | 57.983% |
Sarcopenia § | 1.205 (1.058–1.371) | 20.747% | 1.564 (1.355–1.806) | 36.061% |
Sarcopenic obesity | 1.676 (1.451–1.937) | 40.334% | 2.436 (2.092–2.836) | 58.949% |
Multivariable model | ||||
Normal | Ref | - | Ref | - |
Obesity | 0.920 (0.833–1.016) | NA | 1.044 (0.957–1.140) | NA |
Sarcopenia # | 1.719 (1.429–2.068) | 41.827% | 2.158 (1.792–2.599) | 53.661% |
Sarcopenia § | 1.156 (1.015–1.317) | 13.494% | 1.440 (1.244–1.665) | 30.556% |
Sarcopenic obesity | 1.424 (1.227–1.653) | 29.775% | 1.989 (1.702–2.323) | 49.723% |
Subgroup analysis and sensitivity analysis
Associations of obesity, sarcopenia, and sarcopenic obesity with dementia onset
Women | Men | |||
---|---|---|---|---|
RMST differences (95% CI), year(s) | RMST ratio (95% CI) | RMST differences (95% CI), year(s) | RMST ratio (95%CI) | |
Normal | Ref | Ref | Ref | Ref |
Obesity | 1.114 (1.100, 1.128) | 1.075 (1.071, 1.079) | − 0.170 (− 0.190, − 0.151) | 0.989 (0.988, 0.990) |
Sarcopenia | − 0.080 (− 0.081, − 0.078) | 0.995 (0.995, 0.995) | − 0.192 (− 0.195, − 0.189) | 0.987 (0.987, 0.987) |
Sarcopenic obesity | − 0.109 (− 0.126, − 0.092) | 0.993 (0.992, 0.994) | − 0.511 (− 0.535, − 0.487) | 0.968 (0.966, 0.969) |
Associations of obesity, sarcopenia, and sarcopenic obesity with brain structure
β coefficients and 95% CIs in volume of different brain regions | |||||
---|---|---|---|---|---|
Total brain * | White matter * | Grey matter * | Grey matter in hippocampus | White matter hyperintensities# | |
Women (n = 6328) | |||||
Normal | Ref | Ref | Ref | Ref | Ref |
Obesity | 6751 (2549, 10953) | 8238 (5362, 11114) | − 1486 (− 4026, 1053) | − 39 (− 90, 13) | 0.05 (− 0.02, 0.11) |
Sarcopenia | − 3229 (− 8677, 2220) | − 1849 (− 5568, 1871) | − 1380 (− 4693, 1933) | − 145 (− 212, − 78) | 0.06 (− 0.02, 0.14) |
Sarcopenic obesity | 3429 (− 8426, 15284) | 6675 (− 1440, 14789) | − 3246 (− 10412, 3919) | − 108 (− 254, 38) | 0.16 (− 0.02, 0.34) |
Men (n = 7348) | |||||
Normal | Ref | Ref | Ref | Ref | Ref |
Obesity | − 12677 (− 16464, − 8891) | 2172 (− 428, 4771) | − 14850 (− 17170, − 12528) | − 21 (− 71, 28) | 0.25 (0.19, 0.31) |
Sarcopenia | − 2536 (− 9963, 4892) | 1696 (− 3412, 6804) | − 4232 (− 8779, 316) | − 108 (− 205, − 12) | 0.05 (− 0.06, 0.17) |
Sarcopenic obesity | − 11221 (− 25357, 2915) | 3423 (− 6281, 13127) | − 14640 (− 23309, − 5978) | − 174 (− 358, 10) | 0.26 (0.05, 0.48) |