Table 3.
Associations of multimorbidity defined by the number of diseases with brain volumes.
| Number of diseases* |
P-value | R2 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 | 6 | |||
| Total brain | |||||||||
| Participants | 5388 | 8492 | 7808 | 6110 | 4013 | 2330 | 2506 | ||
| Volume (ml) | 1513 ± 71 | 1505 ± 71 | 1497 ± 72 | 1489 ± 72 | 1483 ± 72 | 1476 ± 72 | 1469 ± 71 | ||
| β (95% CI), Model 1† | Reference | −8·3 (−10·8, −5·9) | −16·1 (−18·6, −13·6) | −23·9 (−26·5, −21·3) | −29·9 (−32·8, −27·0) | −37·4 (−40·9, −33·9) | −44·2 (−47·6, −40·8) | <0·0001 | 0·0305 |
| β (95% CI), Model 2 | Reference | 0·3 (−1·7, 2·3) | −0·2 (−2·3, 1·8) | −1·4 (−3·6, 0·8) | −2·0 (−4·5, 0·4) | −5·0 (−7·9, −2·1) | −6·3 (−9·1, −3·4) | <0·0001 | 0·3407 |
| β (95% CI), Model 3 | Reference | 0·2 (−1·9, 2·2) | −0·4 (−2·5, 1·6) | −1·6 (−3·8, 0·6) | −2·2 (−4·6, 0·3) | −5·1 (−8·0, −2·2) | −6·5 (−9·3, −3·6) | <0·0001 | 0·3463 |
| Grey matter | |||||||||
| Participants | 5388 | 8492 | 7808 | 6110 | 4013 | 2330 | 2506 | ||
| Volume (ml) | 807 ± 46 | 801 ± 45 | 794 ± 47 | 788 ± 47 | 783 ± 48 | 778 ± 48 | 770 ± 49 | ||
| β (95% CI), Model 1 | Reference | −6·4 (−8·0, −4·8) | −12·9 (−14·5, −11·3) | −19·0 (−20·8, −17·3) | −23·9 (−25·8, −21·9) | −29·6 (−31·9, −27·4) | −37·1 (−39·3, −34·9) | <0·0001 | 0·0474 |
| β (95% CI), Model 2 | Reference | −0·1 (−1·4, 1·1) | −1·4 (−2·6, −0·1) | −2·8 (−4·1, −1·5) | −3·7 (−5·2, −2·3) | −6·1 (−7·9, −4·3) | −9·6 (−11·3, −7·9) | <0·0001 | 0·4453 |
| β (95% CI), Model 3 | Reference | −0·2 (−1·4, 1·0) | −1·4 (−2·6, −0·1) | −2·8 (−4·1, −1·5) | −3·7 (−5·1, −2·2) | −5·8 (−7·6, −4·1) | −9·4 (−11·1, −7·6) | <0·0001 | 0·4517 |
| White matter | |||||||||
| Participants | 5388 | 8492 | 7808 | 6110 | 4013 | 2330 | 2506 | ||
| Volume (ml) | 706 ± 40 | 704 ± 40 | 703 ± 41 | 701 ± 41 | 700 ± 41 | 698 ± 41 | 699 ± 41 | ||
| β (95% CI), Model 1 | Reference | −1·9 (−3·3, −0·5) | −3·3 (−4·7, −1·8) | −4·9 (−6·4, −3·4) | −6·1 (−7·7, −4·4) | −7·7 (−9·7, −5·8) | −7·2 (−9·1, −5·3) | <0·0001 | 0·0031 |
| β (95% CI), Model 2 | Reference | 0·5 (−0·9, 1·8) | 1·1 (−0·2, 2·5) | 1·4 (−0·1, 2·8) | 1·7 (0·1, 3·3) | 1·1 (−0·8, 3·0) | 3·4 (1·5, 5·2) | 0·0149 | 0·109 |
| β (95% CI), Model 3 | Reference | 0·3 (−1·0, 1·7) | 1·0 (−0·4, 2·3) | 1·2 (−0·3, 2·6) | 1·5 (−0·1, 3·1) | 0·8 (−1·1, 2·7) | 2·9 (1·0, 4·8) | 0·0642 | 0·1115 |
| Hippocampus | |||||||||
| Participants | 5388 | 8492 | 7808 | 6110 | 4013 | 2330 | 2506 | ||
| Volume (µl) | 3888 ± 428 | 3875 ± 434 | 3847 ± 439 | 3820 ± 448 | 3811 ± 452 | 3802 ± 445 | 3746 ± 448 | ||
| β (95% CI), Model 1 | Reference | −12·8 (−27·9, 2·2) | −40·4 (−55·7, −25·1) | −67·5 (−83·7, −51·4) | −76·6 (−94·6, −58·6) | −85·7 (−107·1, −64·3) | −141·2 (−162·1, −120·3) | <0·0001 | 0·0073 |
| β (95% CI), Model 2 | Reference | 5·7 (−8·4, 19·7) | −4·9 (−19·2, 9·4) | −16·8 (−32·0, −1·7) | −12·4 (−29·3, 4·6) | −15·0 (−35·2, 5·2) | −55·0 (−74·8, −35·3) | <0·0001 | 0·1416 |
| β (95% CI), Model 3 | Reference | 9·8 (−4·2, 23·7) | 3·0 (−11·2, 17·3) | −6·5 (−21·7, 8·7) | 0·6 (−16·4, 17·5) | 1·8 (−18·4, 22·0) | −31·5 (−51·4, −11·6) | 0·0019 | 0·1528 |
| WMH‡ | |||||||||
| Participants | 5388 | 8492 | 7808 | 6110 | 4013 | 2330 | 2506 | ||
| Volume (ml) | 0·81 ± 0·96 | 0·98 ± 0·99 | 1·06 ± 0·98 | 1·18 ± 0·98 | 1·28 ± 1·00 | 1·41 ± 0·98 | 1·52 ± 0·98 | ||
| β (95% CI), Model 1 | Reference | 0·17 (0·13, 0·21) | 0·26 (0·21, 0·30) | 0·37 (0·33, 0·42) | 0·47 (0·42, 0·53) | 0·61 (0·54, 0·67) | 0·71 (0·66, 0·77) | <0·0001 | 0·0244 |
| β (95% CI), Model 2 | Reference | 0·06 (0·02, 0·09) | 0·07 (0·03, 0·11) | 0·11 (0·07, 0·15) | 0·15 (0·10, 0·19) | 0·24 (0·18, 0·29) | 0·27 (0·22, 0·33) | <0·0001 | 0·1754 |
| β (95% CI), Model 3 | Reference | 0·05 (0·02, 0·09) | 0·06 (0·02, 0·10) | 0·10 (0·06, 0·14) | 0·14 (0·09, 0·18) | 0·22 (0·17, 0·27) | 0·25 (0·19, 0·30) | <0·0001 | 0·1744 |
CI, confidence interval; WMH, white matter hyperintensity.
⁎
Number of diseases was calculated based on the 19 groups of major diseases in Table S3.
†
Coefficients for brain volumes associated with multimorbidity were estimated using general linear regression models. Model 1 was the unadjusted model; Model 2 was adjusted for age and gender; Model 3 was adjusted for Model 2 plus APOE4, education, income, smoking, physical acidity, alcohol consumption, sleep duration, and diet. Horizontal lines indicate the ranges of the 95% CIs and the vertical dash lines indicate the mean of 0·0.
‡
WMH was log-transformed in the analysis given its positively skewed distribution.