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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.
Zhao et al., (2019) [89, 126] 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
Verfaillie et al. (2018) [94, 99, 128] 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.
Verfaillie et al. (2018) [94, 99, 128] 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
  1. SCC Subjective cognitive complaints, ND Neurodegeneration, SMD Subjective memory decline, FTP Flortaucipir, SCD Subjective cognitive decline, CDR Clinical dementia rating, AD Alzheimer’s disease, SMI Subjective memory impairment, CMRglc Cerebral metabolic rates for glucose, ApoE Apolipoprotein E, FCSRT Free and cued selective reminding test, BNT Boston naming test, VOSP Visual object and space perception battery, ToL Tower of London test, CSF Cerebrospinal fluid, IP Isoprostane, SUVR Standardized uptake value ratio, SCI Subjective cognitive impairment, MCI Mild cognitive impairment, aMCI Amnestic MCI, NC Normal control, PET Positron emission tomography, ADNI Alzheimer’s Disease Neuroimaging Initiative, MRI Magnetic resonance imaging, DTI Diffusion tensor imaging, WM White matter, FA Fractional anisotropy, MD Mean diffusivity, RD Radial diffusivity, rs-fMRI Resting-state functional MRI, DMN Default mode network