From: White matter microstructure is altered in cognitively normal middle-aged APOE-ε4 homozygotes
Reference (year) | Methods | Measures | Sample size | Age (years) | Genotype groups | Homozygotes (no.) | Results |
---|---|---|---|---|---|---|---|
Nierenberg et al. (2005) [16] | ROI | FA, AxD, RD | 29 | 67.1 (6.5) | 14 ε4 carriers 15 ε4 noncarriers | 2 | ε4 carriers: ↓ FA and ↑ RD in L parahippocampal gyrus (p = 0.015) |
Persson et al. (2006) [17] | ROI, SPM-VBM | FA | 60 | 66.3 (7.7) | Two analyses: 10 ε4/ε4–10 ε3/ε4–10 ε3/ε3 30 ε4 carriers, 30 ε3/ε3 | 10 | ↓ FA in ε4 carriers: Posterior corpus callosum and fronto-occipital fasciculus No evidence of dose-dependent effect, but not enough data |
Honea et al. (2009) [15] | TBSS | FA | 53 | 73.4 (6.3) > 60 | 39 ε3/ε3 12 ε3/ε4 2 ε4/ε4 | 2 | ↓ FA in ε4 carriers: L parahippocampal gyrus (p < 0.001 uncorrected) |
Smith et al. (2010) [51] | TBSS | FA | 65 | 62.9 (1.3) | 42 ε4 carriers 23 ε4 noncarriers | n/a | ↓ FA in LOAD risk group in many regions (e.g., bilateral inferior fronto-occipital fasciculus, cingulum bundle, splenium) (p < 0.01) |
Gold et al. (2010) [42] | TBSS | MD, FA, RD, AxD | 57 | 58.9 (5.8) | 37 ε4 carriers with FH 20 ε4 noncarriers without FH | n/a | Significant for LOAD risk group only: ↓ FA ↑ RD: inferior longitudinal fasciculus, inferior fronto-occipital fasciculus/uncinate fasciculus (p < 0.001) ↓ FA: Fornix, ↑ MD: Genu and R inferior fronto-occipital fasciculus/inferior longitudinal fasciculus, ↓ AD: Cingulum |
Bendlin et al. (2010) [30] | SPM-VBM | FA, MD | 136 | 69.2 (10.2) | 56 ε4 carriers 80 ε4 noncarriers | n/a | No significant interactions between genotype and age were observed ε4 allele: not significant Family history LOAD + ε4: ↓ FA in multiple brain regions |
Heise et al. (2011) [14] | TBSS | MD, FA, RD, AxD | 73 | (1) Young 28.6 (4.2) (2) Older: 64.9 (7.19) | 17 ε4 carriers, 17 ε4 noncarriers (younger) 16 ε4 carriers, 21 ε4 noncarriers (older) | n/a | ε4 carriers: ↑ MD (older) and ↓ FA (younger) in many regions (e.g., cingulum, corpus callosum) (p < 0.05) |
Ryan et al. (2011) [12] | ROI | FA, ADC | 126 | CN (52–92) | 88 ε4 noncarriers 32 ε4 heterozygotes 6 ε4/ε4 | 6 | ε4 carriers: ↑ ADC with ↑ age in all regions (p < 0.0001) ↓ FA with ↑ age: Frontal, and temporal WM, genu (p < 0.05) |
Westlye et al. (2012) [18] | TBSS | MD, FA, RD, AxD | 203 | 47.6 (14.9) 21.1–69.9 | 30 ε2/ε3 113 ε3/ε3 60 ε3/ε4 | 0 | ε4 carriers: widespread increases in MD and RD no interaction between age and genotype no significant differences between ε2/ε3 and ε3/ε4 |
Adluru et al. (2014) [20] | ROI | MD, FA, RD, AxD | 343 | 61.03 (6.72) 47–76 | 14 ε4/ε4 109 ε4 heterozygotes 220 ε4 noncarriers | 14 | Subjects with FH: higher AxD in ε4 carriers, lower AxD in ε4 non-carriers, both in the uncinate fasciculus ε4 carriers: higher MD in the SLF (older) and in the portion of the cingulum bundle running adjacent to the cingulate cortex, also higher RD in the genu |
Kljajevic et al. (2014) [62] | ROI | FA, MD | 56 | 67.7 (5.9) | 28 ε4 carriers, 28 ε4 noncarriers | n/a | ε4 carriers: higher MD in healthy controls but not in AD (p < 0.001, uncorrected) |
Lyall et al. (2014) [63] | ROI | FA | 645 | 72.70 (0.74) | 2 ε2/ε2 77 ε2/ε3 14 ε2/ε4 376 ε3/ε3 160 ε3/ε4 13 ε4/ε4 | 13 | ε4 carriers: lower FA in right ventral cingulum and left inferior longitudinal fasciculus |
Laukka et al. (2015) [64] | TBSS | FA, MD | 89 | 81.41 (3.01) | 23 ε4 carriers, 66 ε4 noncarriers | n/a | ε4 carriers: lower FA in forceps major and higher MD in corticospinal tract |
Cavedo et al. (2017) [19] | TBSS | MD, FA, RD, AxD | 74 | 68.95 (6.85) | 31 ε4 carriers, 43 ε4 noncarriers | n/a | ε4 carriers: lower FA and higher RD in the cingulum, corpus callosum, inferior fronto-occipital and in the inferior longitudinal fasciculi, also higher MD in the genu, right internal capsule, superior longitudinal fasciculus and corona radiata. |