Table 2 Studies investigating the association between neurological disease and brain ageing
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) | Dementia: n = 1622, 54.3 ± 20.7 yrs.; TBI: n = 8472, 35.3 ± 15.1 yrs.; Sex unknown | SPECT (rs-99mTc-HMPAO) | Regional cerebral perfusion | LR | Dementia & TBI | CA-BEA ↓ of 4.1 yrs. & 0.19 yrs. in Dementia, & TBI, respectively | None |
[68] | J-ADNI study (Japan) | HC: n = 146, 68.3 ± 5.6 yrs., 78♀; sMCI: n = 102 73.4 ± 6.0 yrs., 57♀; pMCI: n = 112, 73.6 ± 5.6 yrs., 65♀; AD: n = 147, 74.1 ± 6.6 yrs., 84♀ | MRI (T1[1.5 T]) | Voxel-wise GM volume | SVR [5-fold] | MCI & AD; cognitive scores; MRI | AD (5.36 yrs), pMCI (3.15 yrs) & sMCI (2.38 yrs) GAP ↑ than HC (0.07 yrs., all p < 0.05). Correlates with cognitive scores & MRI (r ~ 0.24–0.28; all p < 0.001). WM (NS) | None |
[33] | Pooled sample of APOE e4 carriers & non-carriers from ADNI study (Longitudinal; US & Canada) | HC: n = 107, 75.7 ± 8.2 yrs.; sMCI: n = 36, 77.0 ± 4.1 yrs.; pMCI: n = 112, 74.5 ± 7.9 yrs.; AD: n = 150, 74.6 ± 9.1 yrs.; 595-1197 days FU; Sex unknown | MRI (T1[1.5 T]) | Voxel-wise GM volume | RVR | MCI & AD; cognitive scores | AD & pMCI brainAGE ↑ than sMCI & HC at b/line & FU (both p < 0.05). dRate ↑ in pMCI (0.61–1.13 yrs) & ADs (0.90–1.68 yrs) than sMCI & HC (p < 0.05). Correlates with cognition at b/line & FU (MMSE: r ~ − 0.34 to − 0.59; ADAS & CDR-SB: r ~ 0.29 to 0.58; all p < 0.001) | bAge, gender, APOE e4 |
[55] | ADNI study (US & Canada) | AD: n = 102, 75.9 ± 8.3 (55–88) yrs., 55♀; HC: n = 232, 76.0 ± 5.1 (60–90) yrs., 113♀ | MRI (T1[N/S]) | Voxel-wise GM volume | RVR [Data splitting] | Early AD | Early AD brainAGE 10 yrs. ↑ than HC (p < 0.001) | None |
[56] | ADNI study (Longitudinal; US & Canada) | HC: n = 108, 75.6 ± 5.0 yrs., 47♀; sMCI: n = 36, 77.0 ± 6.1 yrs., 6♀; pMCI: n = 112, 74.5 ± 7.4 yrs., 45♀; AD: n = 150, 74.6 ± 7.6 yrs., 74♀; ~ 4 yrs. FU | MRI (T1[1.5 T]) | Voxel-wise WB volume | RVR | MCI, & AD; cognitive scores | pMCI & ADs brainAGE ↑ than HC & sMCI at b/line & FU (both p < 0.05). Strongest correlation with severity in AD (MMSE: r = − 0.46) & cognition in pMCI (ADAS: r = 0.40; both p < 0.001). dRate ↑ in pMCI (1.05 yrs) & ADs (1.51 yrs) than sMCI & HC (p < 0.05) | aScanner, age, gender |
[58] | ADNI study (Longitudinal; US & Canada) | sMCI: n = 62, 76.4 ± 6.2 (58–88) yrs., 13♀; Early-pMCI: n = 58, 73.9 ± 7.0 (55–86) yrs., 25♀; Late-pMCI: n = 75, 75.2 ± 7.3 (56–88) yrs., 27♀ at b/line; 3 yr FU | MRI (T1[1.5 T]) | Voxel-wise GM volume | RVR [Data splitting] | sMCI, early & late pMCI; cognitive scores | sMCI (0.75 yrs), early (8.73 yrs) & late pMCI (5.62 yrs) brainAGE (p < 0.001). ↑ ADAS & CDR at b/line (r ~ 0.20 to 0.23), that ↑ at FU (r ~ 0.24 to 0.48; all p < 0.01). ↓ MMSE at FU only (r ~ − 0.17 to − 0.41; all p < 0.05) | None |
[67] | The Leipzig Research Centre for Civilization Diseases-Adult-Study (Germany) | OCI-norm: n = 729, 59.2 ± 15.2 yrs., 364♀; −mild: n = 632, 58.0 ± 14.9 yrs., 294♀; −major: n = 251, 58.3 ± 15.7 yrs., 115♀ | MRI (T1 & T2*-rs-fMRI [3 T]) | Functional, CT, SA, global & subcortical volume | RF stacking (SVR [5-fold]) | Normal, mild & major OCI | For all models but stacked-function (NS), OCI-major BA score ↑ (1.52 to 8.68 yrs) than -mild (0.74 to 2.82 yrs), & -norm (− 0.52 to 1.32 yrs.; all p < 0.05) | None |
[45] | MTLE cases & controls from the Department of Neurology at NTUH (Taiwan) | Right-MTLE: n = 17, 37.9 ± 8.1 yrs., 8♀; Left-MTLE: n = 18, 37.4 ± 8.5 yrs., 8♀; HC: n = 37, 38.4 ± 8.3 yrs., 20♀ | MRI (DSI [3 T]) | Compact features of 7 diffusion indices & 76 fibre tract bundles | GPR [10-fold] | R & L MTLE; clinical characteristics | R-MTLE GAP (10.94 yrs) ↑ than L-MTLE (2.24 yrs) & HCs (0.82 yrs.; both p < 0.05). L-MTLE comparable to HC (NS). Correlates with age of onset (R: r = − 0.51; L: ρ = 0.59; both p < 0.05), & illness duration (R: r = 0.50, p = 0.040; L: r = − 0.48, p = 0.049). ↑ seizure frequency for R-MTLE only (ρ = 0.64, p = 0.007) | bAge, gender, no. of AED classes, handedness |
[69] | Patients from ECP; & healthy adults from ECP or ADCP (US) | TLE: n = 104, 40.4 ± 11.8 (19–60) yrs., 64♀; HC: n = 151, 53.7 ± 19.4 (18–89) yrs., 88♀ | MRI (T1 & rs-fMRI[3 T]) | CT, SA & volume/rs-correlation matrices | SVR [10-fold] | TLE; clinical characteristics & AEDs | TLE structural & functional GAP 6.6 & 8.3 yrs., respectively. Functional correlates ↑ complex partial seizures (ρ = 0.300) & no. of AEDs (ρ = 0.279; both p = 0.07) | aAge |
[40] | Cases from New York University treatment center, or HEP; community dwelling controls (US, AUS & Canada) | MRE: n = 94, 32.3 ± 13.6 yrs., 46♀; NDE: n = 42, 31.4 ± 11.4 yrs., 21♀; Matched HC: n = 74, 28.9 ± 10.2 yrs., 41♀ | MRI (T1[3T]) | Voxel-wise WB volume | GPR [10-fold] | MRE & NDE; clinical factors | MREs brainAGE 4.5 yrs. ↑ than HC (0 yrs., p = 4.6 × 10–5). NDE comparable to HC (NS). NS with duration. BrainAGE ↓ with ↑ age of MRE onset (− 0.15 yr per year, p = 0.03). | bAge, gender |
[52] | Epileptic or PNES cases, & healthy controls from authors institute (Location unknown) | TLE-NL: n = 164, 45.8 ± 16.6 yrs., 83♀; TLE-HS: n = 63, 43.3 ± 13.7 yrs., 38♀; Ext-FE: n = 45, 35.9 ± 12.0 yrs., 18♀; IGE: n = 30, 28.9 ± 7.7 yrs., 22♀; PME/SGE: n = 5, 31.4 ± 9.8 yrs., 2♀; PNES: n = 11, 31.5 ± 8.6 yrs., 8♀ | MRI (T1[3T]) | Voxel-wise WB volume | SVR [10-fold] | Epilepsy; TLE with/without psychosis; PNES/ MRI(−); PME/JME | GAP ↑ in epileptics than HCs (~ 4.7 to 21.2 yrs., p < 0.01), exception being Ext-FE (NS). ↑ for TLEs with psychosis (10.9 yrs) than without (5.3 yrs.; p < 0.001). PNES comparable to MRI(−) (NS). PME (22.0 yrs) ↑ than JME (9.3 yrs.; no p-value) | bAge, gender |
[51] | Cases with persistent neurological problems following TBI, & healthy controls (Location unknown) | TBI: n = 99, 38.0 ± 12.4 yrs., 27♀; HC: n = 113, 43.3 ± 20.2 yrs., 64♀ | MRI (T1[3T]) | Voxel-wise GM or WM volume | GPR [10-fold (×1000)] | TBI; cognitive function; TSI | TBI PAD ↑ than HC (both p < 0.01). ↑ TSI (GM & WM: r ~ 0.50 to 0.54; both p < 0.001). In TBI, ↑ processing speed (ρ ~ 0.27 to 0.38) & ↓ recall (ρ = − 0.25; all p < 0.05). GM PAD correlates executive function (ρ ~ 0.25 to 0.27; all p < 0.05) | bAge, gender |
[70] | Service members from Iowa City Veterans Affairs Medical Center (Retrospective; US) | With TBI: n = 92, 29.7 ± 7.0 (22–57) yrs., 4♀; Without TBI: n = 34, 31.1 ± 9.2 (22–55) yrs., 4♀ | MRI (T1[3T]) | CT | LR, RF, SVR & GPR [Random half-split (× 10,000)] | TBI & characteristics | TBI GAP ↑ than HCs (all models but RF, p < 0.05). TBI characteristics NS | None |
[28] | Patients scanned at MAGNISM center, or Imperial College London, & healthy controls (Longitudinal; UK, Italy, Austria, Catalonia & Netherlands) | MS & CIS: n = 1204, 39.4 ± 10.8 (15–68) yrs., 771♀, 0.2-15 yrs. FU; HC: n = 150, 37.3 ± 10.0 (23–66) yrs., 82♀, 0.5–6.0 FU | MRI (T1[1.5/3 T]) | Voxel-wise WB volume | GPR [10-fold] | MS & CIS; b/line & annual severity of disability (EDSS) | MS & CIS GAP (10.3 yrs) ↑ than HC (4.3 yrs., p < 0.001). ↑ in SPMS (13.3 yrs). CIS comparable to HC (NS). MS & CIS crate (0.61 yrs) ↑ than HC (− 0.17 yrs., p = 0.016); differs between sub-groups (p = 0.002). GAP 0.64 yrs. per 1 EDSS (p < 0.001). ↑ cRate with ↑ annual EDSS (r = 0.26, p < 0.001) | abAge; bGender, age2, scanner, cohort, treatment, normalized brain volume |
[47] | MS cases & matched controls from local community, or registry (Case-control & longitudinal; Norway) | MS: n = 76, 21–49 yrs., 71%♀. 2 FU approx. 26 & 66mths; HC: n = 235, 26-53 yrs., 72%♀ | MRI (T1[1.5/3 T]) | CT, SA & volume | Xgboost [Nested with 10-fold] | MS; clinical factors; MRI | All but temporal GAP (global & regional: ~ 2.4 to 6.2 yrs) ↑ than HC (all p < 0.05). In MS, ↑ atrophy (global & regional: r ~ 0.28 to 0.41), WMLL (global: r = 0.46; cereb./subcort: r = 0.38) & volume (regional: r ~ − 0.35 to − 0.43; all p < 0.05). Global crate 0.41 yrs. (p = 0.008). ↑ atrophy & WMLL (all global and regional, p < 0.05). GAP & crate not associated with clinical factors (NS) | aAge, age2, gender, scanner |
[59] | Cognition and Neocortical Volume after Stroke (CANVAS; Prospective, AUS) | Stroke (6wks post event): n = 135, 67.4 ± 13.0 yrs., 41♀; HC: n = 40, 68.7 ± 6.6 yrs., 15♀; 3 & 12mth FU | MRI (T1[3T]) | CT, SA & subcortical volume | Stacked RF (SVR) | Ischemic stroke (6wks, 3 & 12mths after event) | 3mths post stroke, BA score was 3.9 to 8.7 yrs. ↑ than HCs (p < 0.01). dRate over 1 yr did not differ between HC & stroke patients (no results provided) | bEducation (yrs) |
[71] | Mild stroke patients attending doubled-blind randomised control trial (Norway) | n = 54, 69.7 ± 7.5 (47.8–82.0) yrs., 14♀; 3wk intervention 6mths after admission | MRI (T1[3T]) | Global & regional CT, SA & volume | Xgboost [10-fold] | Cognitive function & improvement | GAP NS following FDR | abAge, gender; aage2 |
[48] | Cases & healthy controls recruited at hospital, via personnel or local support groups (US) | PD: n = 37, 58.8 ± 10.9 yrs., 17♀; HC: n = 20, 47.0 ± 17.1 yrs., 10♀ | PET (18F-FDG) | CMRGlc & GMR | LR | PD & clinical factors | PDs GAP ↓ than HCs (p < 0.005). ↑ duration (r = − 0.38, p < 0.04), & severity (~r = − 0.39 to − 0.32, p ≤ 0.05). Mean preclinical period of 4.5 yrs. (no details provided) | aAge |