SUPPLEMENTARY ONLINE APPENDIX
Full versions of results tables

Table A1. Comparison of regional brain volumes (raw volumes and expressed as a percentage of cranial capacity) of non-demented adults with DS and healthy controls 
		Mean volume		Mean percentage of cranial volume	
		DS (n=39)	Controls (n=42)	Difference	t	p		DS (n=39)	Controls (n=42)	Difference	t	p	
Cranial volume											
	Left	595.6	708.189	112.589	–9.54	<0.001		n.a.	n.a.				
		(579.6–611.6)	(690.4–726.0)	 				 	 				
	Right	583.3	719.1	135.8	–9.52	<0.001		n.a.	n.a.				
		(570.0–596.6)	(693.4–744.7)	 									
	Total	1179.0	1406.5	227.5	–10.30	<0.001		n.a.	n.a.				
		(1152.3–1205.7)	(1370.6–1442.4)										
Whole brain											
	Left	464.8	538.9	74.1	6.98	<0.001		78.1	76.3	–1.8	–1.76	0.084	
		(448.8–480.8)	(524.4–553.3)	 				(76.2–79.9)	(75.4–77.3)	 			
	Right	460.0	556.9	96.9	7.90	<0.001		79.2	77.6   	–1.6	–1.20	0.234	
		(444.3–475.7)	(537.5–576.3)	 				(77.2–81.2)	(75.9–79.3)	 			
	Total	921.7	1089.6	167.9	8.49	<0.001		78.5	76.7	–1.8	–1.87	0.066	
		(891.5–952.0)	(1063.1–1116.2)	 				(76.8–80.2)	(75.8–77.5)	 			
Frontal lobes		 						 			
	Left	187.6	231.7	44.1	9.24	<0.001		31.5	32.8	1.3	2.03	0.047*	
		(181.2–193.9)	(224.3–239.1)	 				(30.4–32.7)	(32.1–33.5)	 			
	Right	187.5	239.9	52.4	8.46	<0.001		32.3	33.6	1.3	1.61	0.111	
		(180.2–194.9)	(229.6–250.2)	 				(31.2–33.4)	(32.4–34.7)	 			
	Total	373.6	466.9	93.3	9.83	<0.001		31.8	32.9	1.1	1.85	0.070	
		(359.7–387.5)	(453.5–480.3)	 				(30.8–32.9)	(32.4–33.5)	 			
Prefrontal lobes		 						 			
	Left	61.0	77.8	16.8	6.97	<0.001		10.3	11.0	0.7	2.19	0.032*	
		(58.0–64.0)	(73.9–81.7)	 				(9.8–10.7)	(10.5–11.4)	 			
	Right	61.6	80.9	19.3	6.96	<0.001		10.6	11.3	0.7	1.83	0.071	
		(58.6–64.6)	(76.1–85.8)	 				(10.1–11.1)	(10.6–11.9)	 			
	Total	122.0	156.1	34.1	8.84	<0.001		10.4	11.1	0.7	2.17	0.033*	
		(116.4–127.6)	(149.5–162.7)	 				(10.0–10.8)	(10.6–11.4)	 			
Temporal lobes		 						 			
	Left	45.6	53.2	7.6	4.36	<0.001		7.67	7.51	–0.16	–0.63	0.531	
		(45.3–48.2)	(50.7–55.7)	 				(7.3–8.1)	(7.21–7.82)	 			
	Right	46.5	55.5	9.0	4.01	<0.001		7.95	7.75	–0.20	–0.71	0.480	
		(43.7–49.2)	(52.3–58.6)	 				(7.54–8.35)	(7.34–8.15)	 			
	Total	92.1	106.8	14.7	4.42	<0.001		7.80	7.52	–0.28	–1.26	0.210	
		(87.1–97.1)	(102.3–111.3)	 				(7.4–8.2)	(7.3–7.8)	 			
Parietal lobes		 						 			
	Left	175.6	201.3	25.7	5.66	<0.001		29.6	28.5	–1.1	–2.00	0.049*	
		(168.8–182.5)	(194.9–207.8)	 				(28.7–30.5)	(27.9–29.1)	 			
	Right	176.5	206.1	29.6	4.78	<0.001		30.4	28.8	–1.6	–2.16	0.034*	
		(176.5–183.9)	(197.1–215.1)	 				(29.3–31.5)	(27.9–29.8)	 			
	Total	352.1	404.2	52.1	5.71	<0.001		30.0	28.5	–1.5	–2.64	0.010*	
		(338.4–365.8)	(391.5–416.8)	 				(29.1–30.9)	(27.9–29.2)	 			
Occipital lobes		 						 			
	Left	54.7	53.1	–1.6	–0.43	0.667		9.15	7.49	–1.66	–2.90	0.005*	
		(48.6–60.7)	(48.5–57.6)	 				(8.17–10.12)	(6.86–8.11)	 			
	Right	49.9	53.9	4.0	1.1	0.271		8.53	7.49	–1.04	–1.73	0.088	
		(44.7–55.2)	(47.6–60.3)	 				(7.65–9.40)	(6.64–8.33)	 			
	Total	104.6	105.8	1.2	0.171	0.865		8.83	7.49	–1.34	–2.57	0.013*	
		(93.6–115.6)	(97.5–114.0)	 				(7.94–9.72)	(6.91–8.06)	 			
Hippocampus		 						 			
	Left	2.27	2.81	0.54	4.61	<0.001		0.384	0.405	0.021	1.10	0.277	
		(2.14–2.40)	(2.61–3.02)	 				(0.361–0.407)	(0.372–0.438)	 			
	Right	2.29	2.59	0.30	2.75	0.009		0.392	0.372	–0.020	–1.21	0.234	
		(2.15–2.42)	(2.41–2.77)	 				(0.373–0.413)	(0.344–0.400)	 			
	Total	4.58	5.43	0.85	4.17	<0.001		0.389	0.389	0.000	–0.20	0.984	
		(4.34–4.83)	(5.10–5.76)	 				(0.362–0.416)	(0.369–0.409)	 			
Amygdala		 						 			
	Left	1.85	2.20	0.35	3.13	0.003		0.312	0.315	0.003	0.12	0.903	
		(1.69–2.02)	(2.04–2.36)	 				(0.283–0.341)	(0.293–0.336)	 			
	Right	1.83	2.04	0.21	1.76	0.083		0.316	0.293	–0.023	–1.12	0.269	
		(0.65–2.01)	(1.88–2.20)	 				(0.283–0.348)	(0.269–0.318)	 			
	Total	3.67	4.31	0.64	2.9	0.005		0.313	0.308	–0.005	–0.30	0.763	
		(3.34–4.01)	(4.02–4.61)	 				(0.283–0.344)	(0.286–0.330)	 			
Caudate			 						 			
	Left	2.75	3.31	0.56	3.82	<0.001		0.462	0.477	0.015	0.58	0.562	
		(2.56–2.93)	(3.07–3.54)	 				(0.432–0.494)	(0.437–0.517)	 			
	Right	2.70	3.25	0.55	4.29	<0.001		0.463	0.469	0.006	0.24	0.812	
		(2.54–2.85)	(3.03–3.47)	 				(0.438–0.489)	(0.429–0.509)	 			
	Total	5.46	6.49	1.03	4.08	<0.001		0.464	0.468	0.004	0.15	0.883	
		(5.12–5.79)	(6.10–6.89)	 				(0.437–0.492)	(0.434–0.502)	 			
Putamen			 						 			
	Left	4.72	4.47	–0.25	–1.64	0.107		0.802	0.642	–0.160	–5.66	<0.001*	
		(4.52–4.93)	(4.24–4.71)	 				(0.759–0.846)	(0.604–0.680)	 			
	Right	4.36	4.12	–0.24	–1.86	0.069		0.756	0.591	–0.165	–7.40	<0.001*	
		(4.22–4.50)	(3.91–4.34)	 				(0.727–0.785)	(0.556–0.626)	 			
	Total	9.17	8.47	–0.7	–0.28	0.006		0.781	0.605	–0.176	–8.22	<0.001*	
		(8.85–9.50)	(8.10–8.85)	 				(0.750–0.813)	(0.575–0.635)	 			
Cerebellum		 						 			
	Left	47.1	71.9	24.8	17.97	<0.001		7.9	10.2	2.3	10.78	<0.001*	
		(45.3–48.8)	(69.6–74.1)	 				(7.7–8.2)	(9.9–10.5)	 			
	Right	47.3	71.9	24.6	11.77	<0.001		8.1	10.1	2.0	7.43	<0.001*	
		(45.7–49.0)	(68.3–75.5)	 				(7.9–8.4)	(9.6–10.5)	 			
	Total	94.4	145.4	51.0	18.84	<0.001		8.0	10.2	2.2	11.63	<0.001*	
		(91.1–97.7)	(141.0–149.7)	 				(7.8–8.3)	(9.9–10.5)	 			
Lateral ventricles		 						 			
	Left	9.21	7.10	–2.11	–1.65	0.104		1.57	1.00	–0.57	–2.88	0.005*	
		(7.30–11.11)	(5.47–8.73)	 				(1.24–1.91)	(0.77–1.23)	 			
	Right	7.28	6.32	–0.96	–0.45	0.657		1.26	0.90	–0.36	–2.19	0.032*	
		(5.80–8.76)	(4.86–7.78)	 				(1.00–1.53)	(0.68–1.11)	 			
	Total	16.49	14.00	–2.49	–1.16	0.251		1.42	1.00	–0.42	–2.35	0.022*	
		(13.20–19.77)	(11.14–16.86)	 				(1.13–1.71)	(0.79–1.21)	 			
Peripheral CSF		 						 			
	Left	1.59	1.57	–0.02	–0.1	0.919		0.271	0.221	–0.050	–1.50	0.138	
		(1.30–1.89)	(1.24–1.91)	 				(0.221–0.321)	(0.176–0.267)	 			
	Right	1.84	2.43	0.59	1.38	0.177		0.319	0.327	0.008	0.13	0.897	
		(1.44–2.24)	(1.64–3.21)	 				(0.248–0.391)	(0.228–0.426)	 			
	Total	4.11	4.04	–0.07	–0.11	0.916		0.349	0.282	–0.067	–1.44	0.156	
		(3.12–5.09)	(3.30–4.88)	 				(0.267–0.431)	(0.233–0.330)	 			
     Where regional brain volumes are expressed as mean percentages of cranial volume, and are presented for left or right (rather than total), these are expressed as percentages of cranial volume of that side only, rather than as a percentage of total cranial volume.
     95% confidence intervals are given in parentheses.
     * Significant group difference.  

Table A2. Age-related differences in regional brain volumes, and group differences in brain ageing, in non-demented adults with DS and healthy controls
		DS		Controls		Difference	
		Constant	Slope	t	p	 	Constant	Slope	t	p	 	Slope	t	p	
Whole brain														
	Left	88.76	–0.305	–3.56	0.001		77.21	–0.026	0.37	0.711		0.279	3.79	<0.001†	
		(84.00–93.52)	(–0.435 to –0.175)				(74.44–79.99)	(–0.103 to 0.052)				(0.132–0.426)			
	Right	90.27	–0.313	–3.51	0.001		78.8	–0.035	–1.33	0.191		0.278	2.66	0.010†	
		(84.59–95.95)	(–0.466 to –0.160)				(73.58–84.03)	(–0.181 to 0.111)				(0.070–0.486)			
	Total	89.35	–0.306	–3.38	0.002		78.49	–0.052	–1.75	0.088		0.254	3.73	<0.001†	
		(84.74–93.95)	(–0.430 to –0.182)				(75.81–81.17)	(–0.124 to 0.020)				(0.118–0.390)			
Frontal lobes														
	Left	36.68	–0.146	–3.35	0.002		33.19	–0.012	0.10	0.919		0.134	2.67	0.009†	
		(33.40–39.96)	(–0.235 to –0.057)				(31.26–35.13)	(–0.066 to 0.042)				(0.034–0.234)			
	Right	37.17	–0.137	–3.11	0.004		33.95	–0.011	–1.11	0.276		0.126	1.87	0.066	
		(33.57–40.77)	(–0.234 to –0.040)				(30.48–37.41)	(–0.107 to 0.085)				(–0.009 to 0.261)			
	Total	37.01	–0.145	–3.39	0.002		33.26	–0.009	–0.99	0.33		0.136	2.92	0.005†	
		(33.77–40.25)	(–0.233 to –0.058)				(31.51–35.00)	(–0.056 to 0.038)				(0.043–0.230)			
Prefrontal lobes													
	Left	13	–0.078	–4.92	<0.001		11.97	–0.03	–1.14	0.264		0.048	3.79	<0.001†	
		(11.78–14.23)	(–0.111 to –0.045)				(10.59–13.36)	(–0.069 to 0.009)				(–0.002 to 0.099)			
	Right	13.17	–0.072	–4.11	<0.001		11.88	–0.018	–1.19	0.241		0.055	1.75	0.084	
		(11.86–14.48)	(–0.108 to –0.037)				(10.02–13.75)	(–0.070 to 0.034)				(–0.008 to 0.117)			
	Total	13.01	–0.074	–4.57	<0.001		11.63	–0.018	–1.41	0.168		0.056	2.47	0.016†	
		(11.82–14.20)	(–0.106 to –0.041)				(10.49–12.77)	(–0.049 to 0.013)				(0.011–0.101)			
Temporal lobes													
	Left	9.4	–0.049	–3.26	0.002		7.92	–0.012	–0.49	0.626		0.037	1.78	0.085	
		(8.16–10.64)	(–0.083 to –0.016)				(6.99–8.85)	(–0.038 to 0.014)				(–0.005 to 0.079)			
	Right	9.42	–0.042	–2.64	0.012		7.64	0.003	–0.20	0.844		0.045	1.85	0.069	
		(8.14–10.71)	(–0.077 to –0.007)				(6.38–8.89)	(–0.032 to 0.039)				(–0.004 to 0.094)			
	Total	9.42	–0.046	–3.20	0.003		7.83	–0.009	–1.15	0.257		0.037	2.13	0.037†	
		(8.30–10.54)	(–0.076 to –0.016)				(7.10–8.57)	(–0.029 to 0.011)				(0.002–0.072)			
Parietal lobes														
	Left	33.5	–0.11	–2.46	0.019		28.37	0.004	0.48	0.632		0.144	2.48	0.015†	
		(30.71–36.30)	(–0.185 to –0.034)				(26.36–30.38)	(–0.052 to 0.061)				(0.022–0.206)			
	Right	35.82	–0.153	–3.54	0.001		27.98	0.025	0.10	0.92		0.178	2.96	0.004†	
		(32.39–39.26)	(–0.246 to –0.061)				(25.12–30.85)	(–0.055 to 0.105)				(0.058–0.298)			
	Total	34.67	–0.132	–3.14	0.003		29.07	–0.016	–1.00	0.324		0.116	2.66	0.009†	
		(31.91–37.43)	(–0.207 to –0.058)				(27.19–30.96)	(–0.067 to 0.036)				(0.029–0.204)			
Occipital lobes													
	Left	8.49	0.019	0.23	0.824		7.75	–0.008	–0.05	0.959		–0.027	–0.52	0.607	
		(5.15–11.84)	(–0.072 to 0.110)				(5.84–9.67)	(–0.062 to 0.046)				(–0.129 to 0.076)			
	Right	7.77	0.022	0.23	0.819		9.23	0.035	–1.63	0.112		–0.073	–1.38	0.171	
		(4.78–10.75)	(–0.060 to 0.103)				(6.69–11.77)	(–0.123 to 0.019)				(–0.179 to 0.033)	 		
	Total	8.13	0.02	0.23	0.816		7.94	–0.013	–0.77	0.444		–0.034	–0.74	0.461	
		(5.07–11.18)	(–0.063 to 0.103)				(6.25–9.64)	(–0.060 to 0.033)				(–0.124 to 0.057)			
Hippocampus														
	Left	0.395	0	–0.74	0.465		0.36	0.001	1.47	0.155		0.002	0.97	0.337	
		(0.318–0.475)	(–0.002 to 0.002)				(0.256–0.463)	(–0.001 to 0.004)				(–0.002 to 0.005)			
	Right	0.394	0	–0.67	0.508		0.368	0	0.02	0.984		0	0.12	0.908	
		(0.325–0.464)	(–0.002 to 0.002)				(0.281–0.455)	(–0.002 to 0.002)				(–0.003 to 0.003)			
	Total	0.412	–0.001	–1.18	0.246		0.356	0.001	0.58	0.57		0.002	1.13	0.261	
		(–0.345 to 0.480)	(–0.003 to 0.001)				(0.273–0.439)	(–0.001 to 0.003)				(–0.001 to 0.004)			
Amygdala														
	Left	0.284	0.001	0.24	0.815		0.305	0	0.62	0.542		–0.001	–0.31	0.757	
		(0.183–0.386)	(–0.002 to 0.004)				(0.236–0.374)	(–0.002 to 0.002)				(–0.004 to 0.003)			
	Right	0.257	0.002	0.80	0.429		0.275	0.001	0.30	0.764		–0.001	–0.62	0.535	
		(0.149–0.366)	(–0.001 to 0.005)				(0.200–0.350)	(–0.001 to 0.002)				(–0.005 to 0.003)			
	Total	0.271	0.001	0.51	0.612		0.262	0.001	1.21	0.238		0	0.01	0.993	
		(0.170–0.373)	(–0.002 to 0.004)				(0.197–0.327)	(0.000–0.003)				(–0.003 to 0.003)			
Caudate														
	Left	0.428	0.001	0.29	0.773		0.531	–0.002	–0.78	0.445		–0.003	–1.12	0.267	
		(0.323–0.533)	(–0.002 to 0.004)				(0.397–0.665)	(–0.005 to 0.002)				(–0.007 to 0.002)			
	Right	0.47	0	–0.76	0.455		0.42	0.001	0.65	0.523		0.002	0.78	0.437	
		(0.384–0.555)	(–0.003 to 0.002)				(0.285–0.554)	(–0.002 to 0.005)				(–0.002 to 0.006)			
	Total	0.446	0.001	–0.06	0.954		0.473	0	–0.54	0.596		–0.001	–0.36	0.719	
		(0.351–0.540)	(–0.002 to 0.003)				(0.363 to –0.003)	(–0.003 to 0.003)				(–0.004 to 0.003)			
Putamen														
	Left	0.923	–0.003	–2.27	0.03		0.71	–0.002	–1.04	0.311		0.001	0.58	0.562	
		(0.773–1.073)	(–0.007 to 0.001)				(0.593–0.827)	(–0.005 to 0.001)				(–0.004 to 0.006)			
	Right	0.832	–0.002	–2.64	0.013		0.629	–0.001	–1.11	0.28		0.001	0.57	0.569	
		(0.738–0.935)	(–0.005 to 0.001)				(0.519–0.739)	(0.004–0.002)				(–0.003 to 0.005)			
	Total	0.91	–0.004	–4.53	<0.001		0.643	–0.001	–1.54	0.135		0.003	1.52	0.134	
		(0.812–1.008)	(–0.006 to –0.001)				(0.551–0.736)	(–0.003 to 0.001)				(–0.001 to 0.006)			
Cerebellum														
	Left	8.52	–0.017	–1.93	0.061		10.46	–0.009	0.19	0.853		0.008	0.42	0.675	
		(7.61–9.43)	(–0.042 to 0.008)				(9.47–11.46)	(–0.038 to 0.020)				(–0.029 to 0.045)			
	Right	8.47	–0.01	–1.79	0.082		9.82	0.007	0.04	0.967		0.017	0.74	0.464	
		(7.62–9.32)	(–0.033 to 0.014)				(8.43–11.21)	(–0.032 to 0.046)				(–0.028 to 0.062)			
	Total	8.52	–0.014	–1.96	0.058		9.9	0.01	0.79	0.433		0.023	1.38	0.172	
		(7.67–9.36)	(–0.037 to 0.009)				(9.02–10.78)	(–0.015 to 0.035)				(–0.010 to 0.057)			
Lateral ventricles													
	Left	0.074	0.043	3.06	0.004		0.449	0.017	1.91	0.064		–0.026	–1.59	0.117	
		(–0.924 to 1.072)	(0.016–0.070)				(–0.238 to 1.144)	(–0.003 to 0.036)				(–0.059 to 0.007)			
	Right	0.118	0.033	2.97	0.005		0.369	0.016	1.77	0.085		–0.017	–1.2	0.233	
		(–0.681 to 0.918)	(0.011–0.055)				(–0.277 to 1.015)	(–0.003 to 0.034)				(–0.045 to 0.011)			
	Total	0.097	0.038	3.13	0.003		0.465	0.015	1.83	0.074		–0.022	–1.6	0.114	
		(–0.775 to 0.969)	(0.014–0.062)				(–0.142 to 1.073)	(–0.001 to 0.032)				(–0.050 to 0.006)			
Peripheral CSF													
	Left	0.256	0	0.10	0.924		0.166	0.002	1.02	0.319		0.001	0.39	0.698	
		(–0.083 to 0.430)	(–0.004 to 0.005)				(0.025–0.307)	(–0.002 to 0.005)				(–0.005 to 0.007)			
	Right	0.157	0.005	1.42	0.166		0.491	–0.005	–1.20	0.241		–0.009	–1.82	0.074	
		(–0.091 to 0.405)	(–0.002 to 0.012)				(0.189–0.794)	(–0.013 to 0.003)				(–0.020 to 0.001)			
	Total	0.032	0.009	2.51	0.017		0.31	–0.001	–0.53	0.601		–0.01	–2.43	0.018†	
95% confidence intervals given in parentheses.
† Significant group-by-age interaction.