From: Factors associated with brain ageing - a systematic review
Reference | Study (Design, country) | n, Mean age ± SD (Range), Sex, Other information | Modality (Protocol) | Features | Model (Cross-validation) | Exposure | Main findings outcome | Adjustments |
---|---|---|---|---|---|---|---|---|
[27] | Multisite psychiatric database (Retrospective; US) | SZ: n = 657, 30.5 ± 13.7 yrs.; ADHD: n = 1462, 21.2 ± 15.5 yrs.; MDD: n = 4753, 38.4 ± 17.0 yrs.; BD: n = 2524, 31.9 ± 16.1 yrs.; CAD: n = 1089, 26.6 ± 10.4 yrs.; AUD: n = 1457, 38.4 ± 14.6 yrs.; GAD: n = 6457, 32.6 ± 17.3 yrs.; Sex unknown | SPECT (rs-99mTc-HMPAO) | Regional cerebral perfusion | LR | Psychiatric co-morbidities | ↑ CA-BA in SZ (−4.0 yrs), CAD (− 2.8 yrs) BD (− 1.7 yrs), ADHD (− 1.4 yrs), AUD (− 0.6 yrs) & GAD (− 0.5 yrs); ↓ in MDs (0.85 yrs) | None |
[44] | In- or out-patient services & matched controls (Germany) | MDD: n = 38, 45.7 ± 15.7 (19–66) yrs., 21♀; HC: n = 40, 42 ± 13.2 (21–73) yrs., 20♀ | MRI (T1[3T]) | Voxel-wise GM volume | RVR | MDD without axis I/II co-morbidity | NS BrainAGE | aScanner |
[43] | Cases and controls from multiple ENIGMA MDD cohorts (Spain, Germany, UK, US, Canada, AUS, Brazil) | MDD: n = 2675, 43.08 ± 14.0 yrs., 1689 ♀; HC: n = 2126, 40.99 ± 15.82 yrs., 1199 ♀ | MRI (T1[1.5/3 T]) | CT, SA, subcortical GM volume, lateral ventricles, ICV | RR [Data splitting & 10-fold] | MDD & clinical characteristics | GAP ↑ in MDDs (b = 1.08, p < 0.0001). ↑ in first episode (b = 1.22), recurrent depression (b = 0.97), remittance (b = 2.19), current MDD (b = 1.47), AD use (b = 1.36), AD free (b = 0.67), early, mid & late age of onset (~b = 0.91–1.21) respectively (all p < 0.05). NS with severity | bAge, age2, sex, site |
[60] | Community dwelling adults from 1 of 6 studies (US) | n = 185, 64.9 ± 8.3 yrs., 91♀ | MRI (T1[3T]) | Voxel-wise WB volume | RVR | Depression | ↑ BrainAGE (r = 0.23, p = 0.01) | bAge, gender, diabetes duration |
[37] | Cases & matched controls from LeAD study (Germany) | HC: n = 97, 43.7 ± 10.8 (21–65) yrs., 16♀; AlcD: n = 119, 45.0 ± 10.7 (20–65) yrs., 18♀ | MRI (T1[3T]) | Cortical & subcortical GM volume | MRR [LOO] | AlcD; lifetime alcohol consumption | 60-69 yr AlcD GAP 11.7 yrs. ↑ than HCs (p < 0.01). NS in AlcD < 39 yrs. 71 standard drinks correspond to approximately ½ day of GAP in AlcD (β = 0.56, p = 0.03) | aGender, site, smoking, LC, general health; bAge |
[32] | Icelandic dataset (Iceland) | HC: n = 291; SZ: n = 68; ID: n = 6; ASD: n = 10; BD: n = 31; Age & sex unknown | MRI (T1[1.5 T]) | Voxel-wise MNI, Jacobian map, GM & WM volume | CNN [Data splitting] | SZ, ID, ASD, & BD | SZ GAP 2.2 yrs. ↑ than HC (2.3y vs. 0.1 yrs.; p < 0.01). NS for ID, ASD, & BD | aAge, sex, TICV |
[38] | Cases from the Early Stages of Schizophrenia; community dwelling controls (Czech Republic) | FEP: n = 120, 27.0 ± 4.9 (18–35) yrs., 46♀; HC: n = 114, 25.7 ± 4.0 (18–35) yrs., 51♀ | MRI (T1[3T]) | Voxel-wise WB volume | RVR | FEP | FEP directly associated with BrainAGE (B = 1.15 yrs., p <  0.01) | bAge |
[41] | 1) Cases from the Early Stages of Schizophrenia & matched controls (Czech Republic); 2) HR offspring from ORBIS, & controls from similar SES (Canada, Prague) | 1) FEP: n = 43, 27.1 ± 4.9 yrs., 17♀; HC: n = 43, 27.1 ± 4.4 yrs., 17♀; 2) HR: n = 48, 20.9 ± 4.2 yrs., 29♀; Early BD: n = 48, 23.1 ± 4.5 yrs., 33♀; HC: n = 60, 23.4 ± 2.9 yrs., 36♀ | MRI (T1[1.5/3 T]) | Voxel-wise WB volume | RVR | FEP; HR & early BD | 1) FEP BrainAGE 2.64 yrs.; HC −0.01 yrs. (Cohens D = 0.64, p = 0.008); 2) HR & early staged BDs comparable to HC (− 0.96, −1.02 yrs. & 0.25 yrs., respectively; NS) | bAge |
[66] | Patients, at risk, & healthy adults from Munich or FePsy database (Retrospective; Germany, Switzerland) | HC: n = 437, 32.6 ± 10.9 yrs., 214♀; ARMS: n = 89, 24.9 ± 5.8 yrs., 33♀; SZ: n = 141, 28.5 ± 7.3 yrs., 33♀; MDD: n = 104, 42.3 ± 12.0 yrs., 52♀; BPD: n = 57, 25.6 ± 6.7 yrs., 57♀ | MRI (T1[1.5 T]) | Voxel-wise GM volume & density | SVR [Repeated (×10) nested 10-fold] | SZ, MDD, BPD, & ARMS; SZ disease stage & clinical factors | SZ (5.5 yrs), MD (4.0 yrs), BPD (3.1 yrs), & ARMS (1.7 yrs) GAP ↑ than HC (all p <  0.05). ↓ age of onset for MDs (r = − 0.26) & BPDs (r = − 0.34; both p < 0.002). RE- (6.4 yrs), RO-SZ (4.2 yrs), & L-ARMS (2.7 yrs) GAP ↑ than E-ARMS (all p < 0.05). ↑ severity in SZ (r ~ 0.20 to 0.26), BPD (r ~ 0.37 to 0.47), & RO-SZ (r ~ 0.27 to 0.30; all p < 0.05) | None |
[49] | Cases from in- or out-patient services, & community dwelling controls (Germany) | SZ: n = 45, 33.7 ± 10.5 (21.4–64.9) yrs., 16♀; BD: n = 22, 37.7 ± 10.7 (23.8–57.7) yrs., 12♀; HC: n = 70, 33.8 ± 9.4 (21.7–57.8) yrs., 30♀ | MRI (T1[1.5 T]) | Voxel-wise GM volume | RVR [Data splitting] | SZ & BD | SZ brainAGE (2.56 yrs) ↑ than BD (− 1.25 yrs) & HC (− 0.22 yrs.; both p = 0.01). BD comparable to HC (NS). SZ♂(3.37 yrs) ↑ than SZ♀(1.07 yrs.; no p-value) | bGender |
[30] | 1&2) Utrecht Schizophrenia Project, First-Episode Schizophrenia Research Program or GROUP (Longitudinal); 4) Cases & controls from exercise based RCT (both Netherlands) | 1&2) SZ: n = 341, 29.5 ± 10.0 yrs.; HC: n = 386, 34.1 ± 11.8 yrs., at b/line (1-13 yrs. FU); 4) HC: n = 55; SZ: n = 60, 19-48 yrs.; Sex unknown | MRI (T1[1.5/3 T]) | Voxel-wise GM density | SVR [Nested-LOO] | SZ & clinical factors | 1&2) SZ GAP + 3.08 yrs. at b/line; ↑ at FU (change = 1.24 yrs.; crate = 1.36 yrs). Associated with severity & antipsychotic dose at FU (both p < 0.0025). Five yrs. post onset, crate ↓ from 2.5 to 1 yr (no p-value). Associated with severity, no. & duration of hospitalisations, & cumulative antipsychotics (all p <  0.0025) 4) SZ GAP + 5.59 yrs | None |
[34] | Two independent samples of outpatients, & healthy adults from CAMH (Canada) | 1) HC: n = 41; SSD: n = 81, 20–83 yrs.; BD: n = 53, 18-81 yrs.; 2) HCs: n = 30; SZ: n = 67, 40.6 ± 16.3 yrs.; Sex unknown | MRI (T1&DWI[1.5/3 T]) | CT, FA, & with (1) or without (2) cognitive scores | RF | SDD & BD | 1) SSD GAP (7.8 yrs) ↑ than HCs (0.67 yrs) & BDs (0.14 yrs.; both p = 0.001). BDs comparable to HCs (no p-value). 2) SZ GAP (6.12 yrs) ↑ than HC (1.8 yrs., p = 0.005) | None |
[50] | BD cases from registry, Mood Disorders Program, or University treatment clinic; Controls recruited via advertisement (Canada) | Li: n = 41, 47.0 ± 13.8 (20.1–72.3) yrs., 23♀; Non-Li: n = 43, 48.2 ± 11.5 (26.9–74.4) yrs., 26♀; HC: n = 45, 42.3 ± 13.8 (20.8–70.9) yrs., 21♀ | MRI (T1[1.5 T]) | Voxel-wise WB volume | RVR [k-fold] | BD with/without Lithium; treatment response (Aldas < 7) | Non-Li brainAGE 4.10 & 4.96 yrs. ↑ than Li & HC, respectively (both p < 0.01). Li comparable to HC (NS). Li with partial prophylactic response ↓ than non-Li (p = 0.03) | bAge |