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Table 5 Studies investigating the association between genetics 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

[26]

1) Cases recruited from University; controls from NSPN U-Change, or local population; 2) SNORD116 case; controls from 1 of 6 studies (both UK)

1) PWS: n = 20, 23.1 ± 2.4 (19–27) yrs., 6♀; HC: n = 40, 22.9 ± 2.2 (19–29) yrs., 14♀; 2) 1 ♂, 24.5 yrs.; Matched HC: n = 95, 34.0 ± 10.2 (19.9–55.5) yrs., 58♀

MRI (T1[3T])

Voxel-wise WB volume

GPR [10-fold (×1000)]

PWS; SNORD116; clinical characteristics

1) PWS PAD ↑ than HC (7.24 yrs), even when matched for BMI (5.51 yrs.; both p < 0.05). No association with PWS IQ, growth or sex hormones, medications, & behaviour (NS); 2) SNORE116 ↑ than HC (12.03 yrs., no p-value)

bBMI, group differences

[46]

Case-control study on DS (England & Scotland)

DS: n = 46, 42.3 ± 9.8 (28–65) yrs., 41♀; HC: n = 30, 46.2 ± 9.8 (30–64) yrs., 14♀

MRI (T1[1.5 T])

Voxel-wise WB volume

GPR [10-fold (×1000)]

DS; cognitive status; PiB uptake

DS PAD ↑ than HC (b = 7.69, p < 0.001). PiB+ DS (n = 19) 5.29 yrs.; PiB- (n = 27) 0.52 yrs. Cognitive subgroups (i.e., stable, declining/dementia) comparable (NS)

None

[84]

Community dwelling adults recruited at university medical center (Germany)

n = 34, 68.8 ± 5.3 (61–80) yrs., 20♀

MRI (T1[3T])

Voxel-wise WB volume

RVR

APOE e4

E4 carriers brainAGE (0.07 yrs) comparable to non-carriers (− 0.67 yrs.; NS)

None

[33]

ADNI study (Longitudinal; US & Canada)

HC: e4+: n = 26, 75.0 ± −5.1 yrs.; e4-: n = 81, 75.9 ± 4.9 yrs.; sMCI: e4+: n = 14, 77.3 ± 5.6 yrs.; e4-: n = 22, 76.8 ± 6.5 yrs.; pMCI: e4+: n = 78, 74.1 ± 6.5 yrs.; e4-: n = 34, 75.5 ± 9.3 yrs.; AD: e4+: n = 101, 74.1 ± 6.8 yrs.; e4-: n = 49, 75.7 ± 8.9 yrs.; 595-1197 days FU; Sex unknown

MRI (T1[1.5 T])

Voxel-wise GM volume

RVR

APOE e4 carrier status; cognitive function (CDR, ADAS, MMSE)

BrainAGE NS with e4 status at b/line, or FU. Correlates with pMCI cognition at b/line (e4+: CDR & ADAS) & FU (e4+: CDR & ADAS; e4-: ADAS; all p <  0.05). AD cognition at b/line (e4+: MMSE; e4-: MMSE, CDR & ADAS) & FU (e4+/−: MMSE, CDR, ADAS; all p < 0.05). cRate differs between e4 groups (~ − 0.01 to 1.68 yrs. per FU yr; p <  0.05)

bAge, gender

[32]

UK Biobank

Discovery: n = 12,378, 46-79 yrs.; Replication: n = 4456, 47-80 yrs.; Sex unknown

MRI (T1[3T])

Voxel-based MNI, Jacobian map, GM and WM volume

CNN [Data splitting]

Genetic variance

GAP associated with 2 genetic variants in Discovery (rs2435204-G: ß = 0.11; rs1452628-T: ß = -0.08) & Replication (rs2435204-G: ß = 0.08; rs1452628-T: ß = -0.07; all p < 0.01)

aAge, age2, gender, TICV, 40 PCs, head motion, genotyping, study site

  1. aBrain age adjustment; bModel adjustment; cCalculated by regressing time on brain age; AD Alzheimer’s Disease; ADAS Alzheimer’s; Disease Assessment Score [73]; ADNI Alzheimer’s Disease Neuroimaging Initiative; APOE Apolipoprotein E genotype; B/line Baseline; BMI Body mass index; CDR Clinical Dementia Rating [75]; CNN Convolutional neural networks; DS Down Syndrome; e4+/− APOE e4 carriers/non-carriers; FU Follow-up; GM Grey matter; GPR Gaussian process regression; HC Healthy controls; IQ Intellectual quotient; MMSE Mini-Mental State Examination [78]; MNI Montreal Neurological Institute; MRI Magnetic resonance imaging; NS Not significant; NSPN U Change NEuroScience in Psychiatry Network U-Change project; PC Principal-component analysis; PiB+/− [11C]-Pittsburgh compound B positive/negative uptake across the brain; pMCI Progressive mild cognitive impairment; PWS Prader-Willi Syndrome; RVR Relevance vector regression; sMCI Stable mild cognitive impairment; SNORD116 Microdelection of SNORD116 gene cluster; TICV Total intracranial volume; WM White matter; WB Whole brain