Table 2 Summary of structural and diffusion MRI studies
From: Neuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer’s disease
Authors | Definition of SCD | Modality | Design | Sample (mean age ± SD) | Main findings |
|---|---|---|---|---|---|
Jessen et al. (2006) [81] | Memory clinic consultation for < 5 y SCD | T1 MRI | Cross-sectional | NC: n = 14 (66.5 ± 6.4) SCD: n = 12 (66.1 ± 7.3) MCI: n = 15 (68.2 ± 5.5) AD: n = 13 (68.8 ± 9.7) | Atrophy in entorhinal cortex not in hippocampus. |
Saykin et al. (2006) [79] | Consensus evaluation using a composite index (multiple self and informant-based questionnaires) | T1 MRI | Cross-sectional | NC: n = 40 (71.0 ± 5.1) SCD: n = 40 (73.3 ± 6.0) MCI: n = 40 (72.9 ± 7.1) | Decreased gray matter in the MTL, frontotemporal and other neocortical regions in SCD and MCI. reduced hippocampal volumes only in MCI. |
Nunes et al. (2010) [75] | Memory clinic consultation | T1 MRI | Longitudinal (NC: 3.4 years SCD: 3.4 years MCI: 3.7 years) | NC: n = 11 (69.5 ± 5.5) SCD: n = 15 (65.9 ± 7.7) MCI: n = 17 (70.8 ± 6.4) | SCD had decreased hippocampal volume longitudinal. MCI had decrease both in total hippocampal and amygdala volumes. |
Shen et al. (2010) [80] | Consensus evaluation using a composite index (multiple self and informant-based questionnaires) | T1 MRI | Cross-sectional | NC: n = 38 (70.6 ± 5.2) SCD: n = 39 (72.8 ± 6.1) MCI: n = 37 (72.7 ± 7.1) AD: n = 11 (75.6 ± 6.8) | Both MCI group and the AD dementia group showed hippocampal volume reduction compared to NC and SCD. |
Striepens et al. (2010) | Memory clinic consultation for <10 y SCD, informant confirmed | T1 MRI | Cross-sectional | NC: n = 48 (66.3 ± 6.2) SCD: n = 21 (65 ± 7.2) | The SCD had reduced volume of bilateral hippocampus, the bilateral entorhinal cortex and the right amygdala compared to the NC. |
Stewart et al. (2011) [86] | 2 binary questions (SCD when both positive) | T1 MRI | Longitudinal (4 years) | Baseline SCD: n = 1793 (72.4 ± 4.1) Follow-up SCD: n = 1336 (72.0 ± 4.0) | SCD at baseline was associated with subsequent change in hippocampal volume and at follow-up impairment was associated with previous change in hippocampus, CSF and gray matter volume. |
Striepens et al. (2011) [84] | Memory clinic consultation for <10 y SCD, informant confirmed | T1 MRI | Cross-sectional | NC ApoE ɛ4+: n = 16 (65.9 ± 7.2) NC ApoE ɛ4-: n = 56 (67.4 ± 7.7) SCD ApoE ɛ4+: n = 11 (66.8 ± 6.8) SCD ApoE ɛ4-: n = 30 (68.5 ± 7.2) | ApoE ɛ4 carriers with SMI performed worse on the episodic memory and showed smaller left hippocampal volumes. The ApoE ɛ4 carriers without SMI performed better on episodic memory and had larger right hippocampal volumes. |
Scheef et al. (2012) [59] | Memory clinic consultation for <10 y SCD with worry, informant confirmed | T1 MRI; | Longitudinal (NC: 34.6 months SCD: 35.5 months) | Baseline NC: n = 56 (66.4 ± 7.2) SCD: n = 31 (67.6 ± 6.2) Follow-up NC: n = 48 (66.5 ± 7.2) SCD: n = 27 (67.4 ± 6.5) | SCD had reduced gray matter volume in the right hippocampus. |
Kim et al. (2013) [68] | Reason for seeking help: memory or health promotion? | T1 MRI | Cross-sectional | NC: n = 28 (70.7 ± 5.5) SCD: n = 90 (65.8 ± 8.5) | The SCD showed significantly smaller hippocampal and amygdala volumes. Association between lower GDS score and smaller hippocampal volume SCD, and association between higher GDS score and smaller amygdala volume NC. |
Peter et al. (2014) [95] | Memory clinic consultation for <10 y SCD with worry, informant confirmed | T1 MRI | Cross-sectional | NC: n = 53 (67.1 ± 6.1) SCD: n = 24 (66.0 ± 7.1) | SCD showed greater similarity to a dementia gray matter pattern compared with NC. Association between episodic memory decline and a dementia gray matter pattern in SCD. |
Cherbuin et al. (2015) [76] | 1 binary question | T1 MRI | Longitudinal (4 years) | NC: n = 218 (62.7 ± 1.32) W1 SCD: n = 70 (62.1 ± 1.4) W2 SCD: n = 56 (62.4 ± 1.5) W1 + W2 SCD: n = 39 (62.3 ± 1.4) | SCD at baseline was not associated with hippocampal atrophy. SCD at follow-up was associated with greater hippocampal atrophy. |
Meiberth et al. (2015) [91] | Memory clinic consultation for <10 y SCD, informant confirmed | T1 MRI | Cross-sectional | NC: n = 69 (66.1 ± 6.9) SCD: n = 41 (68.9 ± 7.2) | SCD showed thickness reduction in left entorhinal cortex compared to NC. |
Perrotin et al. (2015) [88] | Memory clinic consultation | T1 MRI | Cross-sectional | NC: n = 40 (69.4 ± 6.4) SCD: n = 17 (69.1 ± 8.5) AD: n = 21 (68.3 ± 9.5) | SCD showed TIV-normalized volume decrease in hippocampus compared to NC. |
Schultz et al. (2015) [92] | 1 binary question | T1 MRI | Cross-sectional | SCD: n = 77 (54.3 ± 6.1) NC: n =184 (54.4 ± 6.4) | SCD showed cortical thinning in the entorhinal, fusiform, posterior cingulate, and inferior parietal cortices and reduced amygdala volume compared with NC |
Cantero et al. (2016) [87] | Questionnaire, structured interview | T1 MRI | Cross-sectional | NC: n = 47 (68.1 ± 3.2) SCD: n = 48 (69.6 ± 4.3) | SCD showed decreased volumes of CA1, CA4, dentate gyrus and molecular layer compared to NC. Lower volume of the dentate gyres associates with poorer memory performance. |
Hong et al. (2016) [118] | Memory clinic consultation | T1 MRI DTI | Cross-sectional | Low risk: n = 27 (62.1 ± 7.1) High risk: n = 19 (67.1 ± 6.5) | The high-risk group showed lower FA in the hippocampus, parahippocampal gyrus, supramaiginal gyrus and parts of fronto-temporal lobes, but no gray matter atrophy. |
Jung et al. (2016) [121] | Memory clinic consultation | T1 MRI | Cross-sectional | SMI: n=612(64.9 ± 6.9) | Individuals with different subtype atrophy showed difference in age, gender, vascular risk factors and depression. Combination of these factors classified the temporal atrophy subtype and the minimal atrophy subtype with 73.2% and 76.0% accuracy. |
Lee et al. (2016) [117] | Memory clinic consultation | T1 MRI DTI | Cross-sectional | ApoE ɛ4+: n = 13 (66.4 ± 6.3) ApoE ɛ4-: n = 13 (66.2 ± 7.8) | ApoE ɛ4+ SCD showed gray matter atrophy and lower FA compared with ApoE ɛ4- SCD. |
Rogne et al. (2016) [69] | 1 binary question | T1 MRI | Cross-sectional | NC: n = 58 (70.6 ± 6.7) SCD: n = 25 (70.0 ± 9.1) MCI: n = 115 (74.5 ± 7.5) | SCD had larger lateral ventricles and smaller hippocampal volumes than NC. |
Sun et al. (2016) [122] | Memory clinic consultation | T1 MRI rs-fMRI | Cross-sectional | NC: n = 61 (64.1 ± 8.6) SCD: n = 25 (65.5 ± 6.1) | SCD showed higher ALFF but no differences in gray matter volume |
Verfaillie et al. (2016) [93] | Memory clinic consultation | T1 MRI | Cross-sectional | SCD stable: n = 253 (61 ± 9) SCD progression: n = 49 (69 ± 6) | Hippocampal volumes, thinner cortex of the AD-signature and various AD-signature subcomponents were associated with increased risk of clinical progression |
Lauriola et al. (2017) [123] | Subjective cognitive decline Questionnaire | T1 MRI | Cross-sectional | NC: n = 38 (64.0 ± 5.1) SCD: n = 32 (64.8 ± 6.3) | SCD showed increased nighttime wakefulness and reduced sleep efficiency. |
Norton et al. (2017) [124] | Memory Complaint Scald in Spanish | T1 MRI | Cross-sectional | Noncarriers: n = 26 (37.2 ± 6.5) Carriers: n = 26 (35.6 ± 7.7) | PSEN-1 E280A mutation carrier showed decreased hippocampal volume in SCD compared to noncarriers. |
Perrotin et al. (2017) [23] | Memory clinic consultation | 18F-florbetapir PET and T1 MRI | Cross-sectional | NC: n = 35 (65.8 ± 8.6) SCD community: n = 35 (70.8 ± 7.5) SCD clinic: n 28 (67.6 ± 7.7) | SCD showed increased amyloid deposition. Subclinical depression and hippocampal atrophy were associated with medical help seeking. |
Risacher et al. (2017) [125] | Cognitive change Index | 18F-florbetapir and T1 MRI | Cross-sectional | NC: n = 19 (68.5 ± 6.9) SCD: n = 10 (72.2 ± 6.4) MCI: n = 5 (75.7 ± 10.6) | Lower UPSIT scores were associated with increased temporal, parietal tau burden and temporal lobe atrophy in the full sample and in NC and SCD only. |
Hafkemeijer et al. (2013) [73] | Memory clinic consultation | T1 MRI | Cross-sectional | NC = 29 (71.3 ± 3.6) SCD: n = 25 (71.4 ± 9.2) | Reduced gray matter volume in DMN regions. |
Platero et al., (2019) [82] | SCD-I Working Group | T1 MRI | Cross-sectional | NC: n = 70 (70.3 ± 4.5) SCD: n = 87 (71.7 ± 5.1) MCI: n = 137 (73.9 ± 5.0) AD: n = 13 (75.6 ± 5.0) | No differences in hippocampal volumes between NC and SCD. |
Sanchez-Benavid et al., (2018) [72] | 1 binary question and SCD-Q questionnaire | T1 MRI | Cross-sectional | NC: n = 2098 (55.41 ± 6.62) SCD-: n = 319 (55.62 ± 6.22) SCD+: n = 253 (59.10 ± 7.12) | SCD+ subjects showed lower gray matter volumes. |
Sun et al., (2019) [85] | Memory clinic consultation for < 5 y SCD | T1 MRI | Cross-sectional | NC: n = 73 (64.55 ± 5.52) SCD: n = 65 (65.85 ± 4.85) | Decreased total cortical volumes and cortical surface area in SCD. SCD ApoE ɛ4 carriers showed additive reduction in the right cortical surface area. |
Tepest et al., (2018) [83] | Memory clinic consultation | T1 MRI | Cross-sectional | NC: n = 13 (67.5 ± 5.5) SCD: n = 14 (66.4 ± 7.3) MCI: n = 15 (68.2 ± 5.4) AD: n = 12 (69.2 ± 10.0) | No differences in hippocampal surface between SCD and NC. |
Tijms et al., (2018) [100] | Memory clinic consultation | T1 MRI | Cross-sectional | sSCD: n = 100 (67 ± 8) pSCD : n = 122 (68 ± 8) | Lower network parameter values related with increased risk for progression. |
Rooden et al., (2018) [74] | Memory clinic consultation | T1 MRI | Cross-sectional | NC: n = 42 (68 ± 9.2) SCD: n = 25 (68 ± 9.1) | SCD showed hippocampal atrophy. |
SCD-I Working Group | T1 MRI | Cross-sectional | NC: n = 42 (64.24 ± 6.16) SCD: n = 35 (64.53 ± 7.29) aMCI: n = 43 (67.47 ± 10.03) AD: n = 41 (68.88 ± 7.86) | No difference in hippocampal volume between NC and SCD. | |
Ryu et al. (2017) [78] | Memory clinic consultation | T1 MRI and DTI | Cross-sectional | NC: n = 27 (70.6 ± 6.1) SCD: n = 18 (69.9 ± 6.3) | SCD showed lower entorhinal cortical volumes and lower FA and higher MD in the hippocampal body and entorhinal WM compared with NC. |
Fan et al. (2018) [77] | Memory clinic consultation | T1 MRI and DTI | Cross-sectional | NC: n = 34 (67.8 ± 7.4) SCD: n = 43 (66.1 ± 7.0) aMCI: n = 44 (73.9 ± 8.0) | SCD showed cortical atrophy and decreased mean FA. |
Niemantsverdriet et al. (2018) [127] | Criteria by SCD-I | T1 MRI | Cross-sectional | NC: n = 93 (67.3 ± 8.5) SCD: n = 102 (68.6 ± 9.8) MCI: n = 379 (74.6 ± 8.0) AD: n = 313 (77.5 ± 8.0) | Baseline whole brain, gray matter, cortical gray matter and increased CSF volumes predicted cognitive impairment |
Referred by general practitioners or medical specialists | T1 MRI | Cross-sectional | SCD: n = 233 (52.8 ± 9.2) | SCD with faster subsequent memory loss was associated with thinner cortex of the frontal and occipital cortices. | |
Memory clinic consultation | T1 MRI | Cross-sectional | SCD: n = 231 (63.0 ± 9.2) | SCD with lower network size was associated with steeper decline in language. | |
Yue et al. (2018) [71] | 1 binary questions | T1 MRI | Cross-sectional | NC: n = 67 (67.7 ± 6.6) SCD: n =111 (69.8 ± 7.6) MCI: n = 30 (75.5 ± 7.6) | The SCD showed decreased right hippocampal and amygdala volume than NC. Right hippocampal and amygdala volume was correlated to MMSE and MoCA in SCD. |
Lee et al. (2016) [117] | Memory clinic consultation | T1 MRI DTI | Cross-sectional | ApoE ɛ4+: n = 13 (66.4 ± 6.3) ApoE ɛ4-: n = 13 (66.2 ± 7.8) | ApoE ɛ4+ SCD showed gray matter atrophy and lower FA compared with ApoE ɛ4- SCD. |
Brueggen et al., (2019) [111] | Memory clinic consultation | T1 MRI, DTI | Cross-sectional | NC: n = 93 (68.5 ± 5.1) SCD: n = 98 (71.3 ± 5.9) MCI: n = 45 (72.3 ± 5.7) AD: n = 35 (73.5 ± 6.8) | SCD showed higher MD, lower MO and FA. |
Kiuchi et al., (2014) [114] | Memory clinic consultation | T1 MRI, DTI | Cross-sectional | NC: n = 41 (75.2 ± 5.34) SCD: n = 28 (70.5 ± 7.30) MCI: n = 43 (74.6 ± 6.40) AD: n = 39 (73.2 ± 7.98) | No differences between NC and SCD. |
Li et al., (2016) [109] | SCD-I Working Group | DTI | Cross-sectional | NC: n = 37 (65.1 ± 6.8) SCD: n = 27 (65.3 ± 8.0) aMCI: n = 35 (69.2 ± 8.6) AD: n = 25 (68.3 ± 9.4) | SCD showed decreased FA, increased MD and RD. |
Ohlhauser et al., (2019) [112] | Cognitive Change Index test | Cross-sectional | NC: n = 44 (72.49 ± 6.37) SCD: n = 30 (72.94 ± 4.79) | SCD showed lower WM integrity and DTI metrics related with executive function in SCD. | |
Viviano et al., (2019) [115] | Memory clinic consultation | Cross-sectional | NC: n = 48 (66.96 ± 8.79) SCD: n = 35 (68.51 ± 7.66) | No differences in diffusion measures between SCD and NC | |
Yasuno et al., (2015) [113] | Memory clinic consultation | Cross-sectional | NC: n = 30 (72.2 ± 4.8) SCD: n = 23 (69.6 ± 8.0) | SCD showed reduced WM connections. | |
Selnes et al (2012) [116] | Memory clinic consultation | T1 MRI and DTI | Cross-sectional | NC: n = 21 (49 - 77) SCD: n = 16 (45 - 71) MCI: n = 50 (45 - 77) | SCD had higher DR and MD in posterior cingulate, retrosplenial and middle cortices. |
Shu et al (2018) [119] | Memory clinic consultation | DTI | Cross-sectional | NC: n = 51 (62.2 ± 9.1) SCD: n = 36 (63.5 ± 8.7) | SCD had lower global and local efficiency and reduced rich-club and local connections which were correlated with the impaired memory performance. |
Wang et al. (2012) [110] | Memory clinic consultation | DTI | Cross-sectional | NC: n = 35 (71.6 ± 5.2) SCD: n = 29 (73.4 ± 6.3) MCI: n = 28 (74.3 ± 5.8) | SCD had FA, DR, DA and MD values that were intermediate to the MCI and NC. |
Yan et al. (2018) [120] | Memory clinic consultation | DTI | Cross-sectional | NC: n = 62 (63.3 ± 8.1) SCD: n = 47 (65.3 ± 8.4) aMCI: n = 60 (67.3 ± 9.4) d-AD: n = 55 (70.9 ± 9.8) | SCD showed disrupted peripheral regions and reduced connectivity similar to MCI and dementia due to AD. The rich club organization remain stable in the earliest stage only in SCD |