Table 3 Studies investigating health, physical and biological markers, hormones and medications, and disease
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 |
|---|---|---|---|---|---|---|---|---|
[82] | Co-morbidity in Relation to AIDS (COBRA; UK & Netherlands) | HIV+: n = 162, 56 (51–62) yrs., 9♀; HIV-: n = 105, 55.8 (50–62) yrs., 6♀ | MRI (T1[3T]) | Voxel-wise WB volume | GPR [10-fold (×1000)] | HIV; clinical & health factors | HIV+ PAD ↑ than HIV- (b = 3.31, p < 0.01). NS with clinical or health factors | bScanner, gender, ICV, smoking |
[39] | HIV positive & negative adults from a larger study (K23 MH095661) | HIV+: n = 70, 50.7 ± 11.9 (24–76) yrs., 12♀; HIV-: n = 34, 53.3 ± 10.3 (24–66) yrs., 17♀ | MRI (DWI[3 T]) | FA, L1, AD, MD | SVR [10-fold] | HIV; clinical factors; cognitive function | HIV+ GAP ↑ than HIV- (n2 = 0.21, p = 0.001). HIV+ associated with viral load (β = 0.23, p = 0.03), & cognitive function (learning: r = − 0.26; memory: r = − 0.21; both p = 0.03) | aScanner; bAge, gender, duration, HAART, CD4, viral load, comorbidity |
[62] | Central nervous system HIV Anti-Retroviral Therapy Effects Research (CHARTER; Longitudinal; US) | n = 139, median age 44 yrs.(IQR: 44-55 yrs), 19♀; n = 111 with FU cognitive data (mean 3.5 visits) | MRI (T1[1.5 T]) | Voxel-wise WB volume | GPR | HIV; clinical factors; comorbidity; cognitive function, deficit, & change | GAP + 1.17 yrs. ↑ for HIV+ with confounding comorbidity (5.87 yrs., p < 0.01). Trend with prior AIDS (3.03 yrs., p = 0.05). ↑ cognitive deficit (b = 0.011, p = 0.03). No association with cognitive function, or change in function (NS) | bAge, comorbidity, scanner, 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 | Obesity, LDLs, HDLs & triglycerides | ↑ BrainAGE in obese/overweight (B = 0.92, p < 0.01). ↑ in obese/overweight FEPs (3.83 yrs., 95% CI: 2.35–5.31 yrs); ↓ in normal weighted HC (− 0.27 yrs., 95% CI: − 1.22-0.69 yrs). LDL, HDL, & triglycerides 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] | BMI | GAP correlates with ↑ BMI in RO-SZ only (r = 0.36, p < 0.05) | None |
[53] | UK Biobank | n = 19,000, 10,112♀; Age unknown | MRI (T1, rfMRI, tfMRI, T2 FLAIR, dMRI, swMRI [3 T]) | IDP | Non-LR [10-fold] | dBody composition; bone density; blood pressure, heart rate; haemoglobin; health & medications | GAP correlates with body composition, & bone density (r ~ − 0.08 to − 0.18); also observed in ♀ (all -log10P > 8). Correlations with no. treatments/medications, & diabetes (both r = 0.06); also observed in ♂ (all -log10P > 8). Strongest correlation with blood pressure, heart rate, & haemoglobin in ♂ (r ~ 0.08 to 0.11; all -log10P > 8) | aAge, age2, gender |
[19] | Lothian Birth Cohort 1936 (LBC1936; Scotland) | n = 669 (n = 73 deceased), 72.7 ± 0.7 yrs., 317♀ | MRI (T1[3T]) | Voxel-wise WB volume | GPR [10-fold (× 1000)] | Mortality | Deceased ♂ & ♀ PAD 8.13 & 2.07 yrs., respectively. Surviving ♂ & ♀ PAD 3.76 & -1.64 yrs., respectively | None |
[54] | UK Biobank | n = 14,701, 62.6 ± 7.5 yrs., 7914♀ | MRI (T1, rfMRI, tfMRI, T2 FLAIR, dMRI, swMRI [3 T]) | IDP | LASSO [10-fold] | Blood pressure; diabetes & stroke history | ↑ GAP associated with health (DBP: B = 0.05; SBP: B = 0.03; diabetes: B = 2.12; stroke history: B = 2.70; all p < 0.001) | abAge; bAge2, gender, height, volumetric scaling, & tfMRI head motion |
[60] | Community dwelling adults from 1 of 6 studies (Longitudinal; US) | 2DM: n = 98, 64.6 ± 8.1 yrs., 45♀; HC: n = 87, 65.3 ± 8.5 yrs., 46♀, at b/line; 3.8 ± 1.5 yrs. (n = 25) FU | MRI (T1[3T]) | Voxel-wise WB volume | RVR | 2DM; clinical laboratory data | 2DM brainAGE (4.6 yrs) ↑ than HC (p < 0.0001). cRate ↑ by 0.2 yrs. per FU (p = 0.03). In total cohort, ↑ TNFa (r = 0.29, p = 0.01). 2DM correlates hyperglycemia (r = 0.34) & duration (r = 0.31; both p < 0.05) | bAge, gender, hypertension, diabetes duration |
[57] | Males & females from ADNI (US & Canada) | n = 118♂, 75.8 ± 5.3 (60–88)yrs.; n = 110♀, 76.1 ± 4.8 (62–90)yrs | MRI (T1[1.5 T]) | Voxel-wise GM volume | RVR | Physiological & clinical chemistry markers | ♂ brainAGE correlates ↑ BMI, DBP, GGT, & uric acid (r ~ 0.19 to 0.35; all p < 0.05). ♀ correlates ↑ GGT, AST, ALT (r ~ 0.20 to 0.25), & ↓ B12 (r = − 0.17; all p < 0.05) | bGender, age, site |
[83] | Neuromodulatory Examination of Pain and Mobility Across the Lifespan (NEPAL; US) | NCP: n = 14, 71.5 ± 7.3 yrs., 8♀; CP: n = 33, 70.6 ± 5.5 yrs., 27♀ | MRI (T1[3T]) | Voxel-wise WB volume | GPR [10-fold] | CP; pain characteristics; psychological & emotional function | CPs PAD (1.5 yrs) ↑ than NCPs (− 4.0 yrs., p = 0.03). Correlates with positive affect (ρ = − 0.47, p = 0.04) & average intensity of worst pain (r = 0.46, p = 0.03) | bAge, exercise, gender |
[36] | Young postpartum women (Longitudinal; Sweden) | Early-: n = 14, 32.8 ± 4.0 (25–38)yrs.; Late-postpartum: 35 ± 5 days later | MRI (T1[3T]) | Voxel-wise GM volume | RVR | Early & late post-partum; estradiol & progesterone | Late postpartum BrainAGE 5.36 yrs. ↓ than early (p < 0.001). No correlation with estradiol, or progesterone (data not provided) | None |
[61] | Female volunteers with known ovulation cycle, & paired males (Longitudinal) | 7♀, 21–31 yrs.; 7♂, 23-37 yrs. at t1; Scanned at ovulation (t2), midluteal phase (t3) & next menses (t4) | MRI (T1[1.5 T]) | Voxel-wise GM volume | RVR | Menstrual cycle; estradiol & progesterone | BrainAGE differs during cycle (p = 0.03). ↓ From t1–2 (1.27 yrs., p < 0.05); NS from t1–3 (0.5 yrs) & from t1–4 (0.10 yrs). Correlates with estradiol only (r = − 0.42, p < 0.05) | None |
[63] | Community dwelling adults from double-blinded randomised control trial (US) | n = 20, 32.4 ± 6.7 (23–47) yrs., 10♀; 2 two week FU | MRI (T1[3T]) | Voxel-wise GM volume | SVR [10-fold] | Acute Ibuprofen before scan (200 & 600 mg) | Ibuprofen associated with ↓ GAP (200 mg: β = −1.18 yrs., p = 0.005; 600 mg: β = − 1.15 yrs., p = 0.006) | None |