Highlights
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The main imaging features and neuroimaging advances in individuals with SCD related to AD are summarized.
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The symptoms of SCD are associated with specific and distinctive underlying pathological events.
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A preferential vulnerability of AD-signature regions in individuals with SCD are described.
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The risk factors for dementia due to AD may interact with SCD and aggregate brain alterations.
Background
Methods
Standard terminology and diagnostic criteria
Positron emission tomography
β-amyloid deposition
Tau burden
Cerebral glucose metabolism
Authors | Definition of SCD | Modality | Design | Sample (mean age ± SD) | Main findings |
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Amariglio et al. (2012) [29] | E-Cog; MFQ; Composite of 7 questions | PiB-PET | Cross-sectional | SCC: n=131(73.5±6.0) amyloid-: n=97(72.7±5.9) amyloid+: n=34(75.5±6.9) | SCC score relate to cortical PiB binding |
Amariglio et al. (2018) [39] | Composite of 7 questions | PiB-PET | Cross-sectional | All: n=279(73.4±6.1) amyloid-: n=209(72.9±6.0) amyloid+: n=70(70.0±5.7) | Amyloid positivity individuals have pronounced progression of SCD |
Buckley et al. (2016) [41] | MAC-Q scale | PiB-PET 18F-florbetapir PET 18F-flutematamol-PET MRI | Cross-sectional | NC: n=288 amyloid-: n=230(69±5.9) amyloid+: n=58(72±7.2) | High SMD related to greater rates of clinical progression, greater depressive symptom and smaller left hippocampal volume |
Cacciamani et al. (2017) [31] | Composite of 15 questions IQCD ASC AD-NOS | 18F-florbetapir PET MRI FDG-PET | Cross-sectional | High awareness: n=86(76.08±0.36) Low awareness: n=19(76.11±0.82) | No relationship between SCD score and neuroimaging markers; higher amyloid burden and lower cortical metabolism in “high awareness” group |
Chen et al. (2019) [27] | Metamemory in Adulthood questionnaire | 18F-florbetapir PET MRI | Cross-sectional | Total: n=85(66.97±15.11) Negative: n=53(61.25±14.86) Positive: n=32(76.46±9.96) | Poor memory performance mediates the relationship between amyloid and SCD |
Hollands et al. (2015) [37] | MAC-Q Composite of 16 questions | PiB-PET | Cross-sectional | Low Aß: n=224(68.37±5.88) High Aß: n=65(73.46±7.33) | High Aß group show moderate decline in learning and working memory over 18 months. |
McCluskey.et al. (2018) [32] | MAC-Q 1 binary question | 18F-florbetaben PET | Cross-sectional | All: n=112(69.2, 2.5) | Self-reported confusion predicted higher global amyloid burden and regional amyloid in the prefrontal, posterior cingulate, precuneus and the lateral temporal. |
Moreno–Grau et al. (2018) [42] | Cognitive complaints | 18F-florbetaben PET 18F-florbetapir PET | Cross-sectional | ADNI_NC: n=182(73.4±6.3) ADNI_SMC: n=103(72.2±5.6) ADNI_EMCI: n=303(71.3±7.4) ADNI_LMCI: n=157(72.2±7.5) ADNI_AD: n=144(74.4±8.1) FACEHBI_SCD: n=200(65.8±7.1) ADNI_NC: n=182(73.4±6.3) | Higher ApoE ɛ4 carrier in SCD and ApoE ɛ4 dosage explained 9% and 11% cerebral amyloid variation. |
Perrotin et al. (2017) [23] | Composite of 26 questions | 18F-florbetapir PET MRI | Cross-sectional | Controls: n=35(65.6±8.6) SCDcommunity: n=35(70.8±7.5) SCDclinic: n=28(67.6±7.7) | Both groups with high self-reported difficulties has higher amyloid deposition |
Perrotin et al. (2012) [25] | 2 questions | PiB-PET MRI | Cross-sectional | High PiB uptake: n=11(75.73±6.05) Low PiB uptake: n=28(71.89±5.45) | Correlation between memory self-reports and regional PiB uptake in right medial prefrontal, anterior cingulate, right precuneus and posterior cingulate. |
Risacher et al. (2015) [43] | CCI E-Cog | 18F-florbetapir PET FDG-PET MRI | Cross-sectional | NC ApoE ɛ4-: n=132(73.7±6.1) NC ApoE ɛ4+: n=53(71.8±6.4) SMC ApoE ɛ4-: n=71(72.5±5.7) SMC ApoE ɛ4+: n=33(70.3±5.2) EMCI ApoE ɛ4-: n=174(71.6±7.3) EMCI ApoE ɛ4+: n=131(70.0±7.5) | SMC ApoE ɛ4+ show greater amyloid deposition than SMC ApoE ɛ4- |
Rodda et al. (2010) [30] | Memory complain | PiB-PET | Cross-sectional | No presented | No difference in amyloid load between SCI and controls |
Rowe et al. (2010) [28] | 1 binary question | PiB-PET MRI | HC: n=177(71.6±7.4) MCI: n=57(75.5±7.5) AD: n=53(72.6±8.9) HC nMC: n=81(72.0±7.5) HC SMC: n=96(71.2±7.4) | SMC related to elevated PiB in ApoE ɛ4 carriers | |
MFQ CFQ SCCS | PiB-PET | Cross-sectional | SCD: n=14(68.1±4.0) NC: n=84(73.6±5.8) | 57% of SCD and 31% of NC were PiB-positive. SCD had higher PiB retention in frontal cortex, lateral temporal cortex, and parietal cortex. | |
MFQ CFQ SCCS | PiB-PET | Cross-sectional | Total: n=92(81.2±8.4) | MFQ score relate to global PiB retention | |
Timmers et al. (2019) [38] | Memory clinic consultation Intact cognition | 18F-florbetapir PET | Cross-sectional | Total: n=107(64±8) | Higher 18F-florbetapir BPND relates to steeper rate of decline on memory, attention/executive and language |
Verfaillie et al. (2019) [33] | CCI SCF Composite of 4 questions | 18F-florbetapir PET | Cross-sectional | Total: n=106(63.83±7.65) | Higher cortical amyloid deposition relates to SCD-related worries and higher memory deficit awareness but not to SCD questionnaires |
Zwan et al. (2016) [44] | MAC-Q IQCODE-S | PiB-PET 18F-flutematamol PET | Cross-sectional | Low amyloid burden: n=229(71.9±6.5) High amyloid burden: n=78(75.0±7.2) | SMC with younger age and ApoE ɛ4 carriers had higher amyloid burden. |
Swinford et al. (2018) [50] | E-Cog | 18F-flortaucipir PET | Cross-sectional | CN: n=40(76.48±7.211) SMC: n=11(71.55±5.11) EMCI: n=31(75.32±7.29) | Memory concern and the self-perception relate to tau aggregation. |
Cavedo et al. (2018) [60] | Memory complaints | 18F-flortaucipir -PET FDG-PET MRI | Cross-sectional | Women: n=201(76.02±3.24) Men: n=117(76.05±3.85) | Men had higher amyloid load glucose hypometabolism and lower RSFC. |
Gardener et al. (2016) [58] | 1 binary question | FDG-PET | Cross-sectional | All: n=43(66±10.1) Non-SMC: n=23(66±8.9) SMC: n=20 (68±11.4) | Positive association between memory immediate recall and FDG-PET SUVR in the right amygdala in SMC individuals. |
Matias-Guiu et al. (2017) [61] | Memory complaint | FDG-PET | Cross-sectional | HC: n=20(65.0±10.6) SMC: n=9(72.4±10.6) | FCSRT positively correlate with metabolism in the medial and anterior temporal region bilaterally, the left precuneus, and posterior cingulate; BNT results correlate with metabolism in the middle temporal, superior, fusiform, and frontal medial gyri bilaterally; VOSP results relate to the occipital and parietotemporal regions bilaterally; ToL scores correlate to metabolism in the right temporoparietal and frontal regions |
Mosconi et al. (2008) [55] | Structured interview | FDG-PET | Cross-sectional | SMC- ApoE ɛ4-: n=7(63±5) SMC+ ApoE ɛ4-: n=8(60±9) SMC- ApoE ɛ4+: n=7(54±9) SMC+ ApoE ɛ4+: n=6(59±7) | ApoE ɛ4+ carriers had decreased CMRglc and higher CSF IP, P-Tau, T-Tau, and P-Tau/Amyloid42 levels. SMC had reduced CMRglc. ApoE genotype and SMC interacted on lowest PHG CMRglc and the highest CSF IP, P-Tau, and P-Tau/Amyloid42 levels. |
Scheef et al. (2012) [59] | Memory clinic consultation 1 binary question | FDG-PET MRI | Cross-sectional | NC: n=56(66.4±7.2) SMI: n=31(67.6±6.2) | SMI had hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe and gray matter atrophy in the right hippocampus. Association between longitudinal memory decline and reduced glucose metabolism in the right precuneus at baseline. |
Song et al. (2016) [56] | Memory complaint | FDG-PET MRI | Cross-sectional | HC: n=42(68.02±5.44) SMI: n=31(69.94±6.44) MCI: n=47(69.55±6.65) | SMI had hypometabolism in the periventricular regions. SMI had hypometabolism in the parietal, precentral frontal, and periventricular regions. |
Vannini et al. (2017) [57] | MFQ | PiB-PET FDG-PET | Cross-sectional | All: n=251(73.3±6.2) amyloid-: n=190(72.8±6.1) amyloid+: n=61(74.9±6.2) | Correlation between SMCs and FDG metabolism. SMCs interacted with amyloid burden on FDG metabolism in the bilateral medial temporal lobes. |
Structural MRI and diffusion MRI
Gray matter
White matter
Authors | Definition of SCD | Modality | Design | Sample (mean age ± SD) | Main findings |
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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 |
Functional MRI
Resting-state fMRI
Task-based fMRI
Arterial spin labeling
Authors | Definition of SCD | Modality | Design | Sample (mean age ± SD) | Main findings |
---|---|---|---|---|---|
Dummas et al. (2013) [145] | Endorsed more than 20% of the items on the complaint inventory | Task-fMRI | Cross-sectional | NC: n = 11 (56.8 ± 1.9) SCD: n = 12 (57.1 ± 2.3) | SCD had increased activations in middle frontal gyrus, precuneus and cingulate gyrus compared to NC. |
Erk et al. (2011) [146] | Memory clinic consultation | Task-fMRI | Cross-sectional | NC: n = 20 (66.8 ± 5.4) SCD: n = 19 (68.4 ± 5.7) | SCD was associated with a reduction in right hippocampal activation during episodic memory recall in the absence of performance deficits and increased activation of the right dorsolateral prefrontal cortex. |
Rodda et al. (2009) [147] | Self-perceived memory difficulties persistent and severe enough to seek advice despite normal cognition | Task-fMRI | Cross-sectional | NC: n = 10 (68.0 ± 13.5) SCD: n = 10 (64.2 ± 5.6) | SCD exhibited increased activation in left during the divided attention task. |
Hu et al. (2017) [150] | Criteria by SCD-I | Task-fMRI | Cross-sectional | NC: n = 24 (66.5 ± 7.2) SCD: n = 20 (68.3 ± 7.9) | Subtle neuronal network disruptions in SCD. |
Hayes et al. (2017) [149] | Worrisome decline in memory | Task-fMRI | Cross-sectional | NC: n = 41 (67.5 ± 9.1) SCD: n = 23 (68.6 ± 8.2) | SCD showed a more negative subsequent memory effects in the default mode network. |
Dillen et al. (2017) [138] | A cut-off value of≥25 on the memory complaint questionnaire but average scores on neuropsychological tests | rs-fMRI | Cross-sectional | NC: n = 25 (62.4 ± 7.0) SCD: n = 28 (65.8 ± 7.8) Prodromal AD: n = 25 (70.8 ± 6.2) | SCD showed decreased connectivity between DMN and hippocampus. |
Hafkemeijer et al. (2013) [73] | Memory complaints but normal cognition | T1 MRI and rs-fMRI | Cross-sectional | NC: n = 29 (71.3 ± 3.4) SCD: n = 25 (71.4 ± 9.2) | SMC showed increased FC in the default mode network. |
Sun et al. (2016) [122] | Self-reported persistent decline in memory compared with a previous state but normal cognition | T1 MRI and rs-fMRI | Cross-sectional | NC: n = 61 (64.1 ± 8.6) SCD: n = 25 (65.5 ± 6.1) | SCD had higher ALFF values in the left inferior parietal lobule and right middle occipital gyrus than control subjects, which were correlated with verbal episodic memory scores. |
Verfaillie et al. (2018) [128] | 1 binary question | rs-fMRI | Longitudinal (one year) | Baseline NC: n = 56 (64 ± 5) Baseline SCD: n = 68 (64 ± 5) Follow-up NC: n = 29 (65 ± 6) Follow-up SCD: n = 30 (65 ± 6) | SCD showed increased pDMN–MTMS connectivity. Higher connectivity between MTMS and the rest of brain was associated with better baseline immediate memory, attention, and global cognition. Higher MTMS and pDMN–MTMS connectivity were associated with lower immediate memory over time. |
Wang et al. (2013) [139] | Endorsed more than 20% of the items on the Cognitive Complaint Index | rs-fMRI | Cross-sectional | NC: n = 16 (70.7 ± 6.0) SCD: n = 23 (70.1 ± 7.3) MCI: n = 18 (73.7 ± 9.1) | SCD showed decreased DMN connectivity in the right hippocampus compared to NC and higher connectivity compared to MCI. |
Yasuno et al. (2015) [113] | Reisberg criteria | rs-fMRI | Cross-sectional | NC: n = 30 (72.2 ± 4.8) SCD: n = 23 (69.6 ± 8.0) | SCD showed reduced FC in cortical midline structures |
Cavedo et al. (2018) | subjective memory complaints | 18F-florbetapir-PET FDG-PET MRI | Cross-sectional | Women: n=201 (76.02±3.24) Men: n = 117(76.05±3.85) | Men had lower resting-state FC. |
Chiesa et al., (2019) [140] | 2 binary questions | rs-fMRI | Cross-sectional | ApoE ɛ4+: 44 (75.6 ± 3.5) ApoE ɛ4-: 180 (75.5 ± 3.4) | ApoE ɛ4+ showed slower increase in FC in frontal lobes. |
Dillen et al., (2016) [136] | Structural questionnaire | rs-fMRI | Cross-sectional | NC: n = 25 (62.4 ± 7.0) SCD: n = 27 (65.7 ± 7.9) AD: n = 24 (71.0 ± 6.2) | Higher FC from RSC to frontal cortex in SCD. |
Dong et al., (2018) [137] | Memory clinic consultation | rs-fMRI | Cross-sectional | NC: n = 39 (82.89 ± 4.13) SCD: n = 39 (83 ± 4.43) | Lower aFCS in SCD. |
Viviano et al., (2019) [115] | 2 binary questions | rs-fMRI | Cross-sectional | NC: n = 48 (66.96 ± 8.79) SCD: n = 35 (68.51 ± 7.66) | SCD showed lower average FC. |
Eulate el al., (2017) [163] | Memory clinic consultation | ASL | Cross-sectional | NC: n = 32 (72.3 ± 5.6) SCD: n = 28 (67.3 ± 7.8) MCI: n = 34 (73.7 ± 7.5) AD: n = 21 (75.8 ± 6.2) | No differences in CBF between SCD and HC. |
Hays et al., (2018) [162] | Memory clinic consultation | ASL | Cross-sectional | NC: n = 35 (73 ± 6.25) SCD: n = 35 (72.54 ± 5.07) | SCD showed negative associations between verbal memory and CBF. |
Leeuwis et a., (2017) [164] | Memory clinic consultation | ASL | Cross-sectional | SCD: n = 143 (56.69 ± 8.69) MCI: n = 95 (65.24 ± 7.28) AD: n = 161 (65.93 ± 7.04) | No correlation between CBF and cognition. |
Yang et al., (2019) [165] | SCD-I Working Group | rs-fMRI | Cross-sectional | NC: n = 55 (63.41 ± 7.97) SCD: n = 43 (65.09 ± 8.66) aMCI: n = 52 (68.06 ± 9.32) AD: n = 44 (70.98 ± 10.02) | SCD showed lower fALFF. |
EEG/MEG
Authors | Definition of SCD | Modality | Design | Sample (mean age ± SD) | Main findings |
---|---|---|---|---|---|
Alexander et al. (2006) [171] | Memory clinic consultation | EEG | Cross-sectional | NC: n = 79 (63.1 ± 7.9) SCD: n = 100 (64.9 ± 8.7) | SCD showed higher alpha power and changes in wave activity both related to decreased memory. |
Babiloni et al. (2010) [172] | Memory clinic consultation | EEG | Cross-sectional | NC: n = 79 (69.7 ± 0.9) SCD: n = 53 (69.0 ± 1.0) aMCI: n = 92 (72.0 ±) naMCI: n = 51 (73.0 ± 1.1) | SCD showed greater frontal delta sources and lower parietal and occipital theta sources in amplitude. |
Gouw et al. (2017) [173] | Criteria by SCD-I | EEG | Cross-sectional | SCD: n = 63 (66.2 ± 8.2) MCI: n = 142 (68.3 ± 7.4) | In SCD, higher delta and theta power and lower alpha power and peak frequency were associated with clinical progression |
Teipel et al. (2018) [178] | 2 binary questions | EEG and 18F-florbetapir-PET | Cross-sectional | SCD amyloid-: n = 255 (75.9 ± 3.5) SCD amyloid +: n = 63 (76.7 ± 3.5) | Amyloid accumulation does not impair cortical FC in SCD. |
Lopez-Sanz et al. (2016) [175] | Self-reported cognitive concerns, older than 60 | MEG and T1 MRI | Cross-sectional | NC: n = 39 (70.4 ± 3.7) SCD: n = 41 (71.6 ± 4.5) MCI: n = 51 (73 ± 3.7) | SCD and MCI exhibited a similar reduction in alpha band activity compared with NC. MCI showed a slowing in alpha peak frequency compared with both SCD and NC. |
Lopez-Sanz et al. (2017) [168] | Self-reported cognitive concerns, older than 60 | MEG and T1 MRI | Cross-sectional | NC: n = 39 (70.4 ± 3.7) SCD: n = 41 (71.6 ± 4.5) MCI: n = 51 (73 ± 3.7) | SCD and MCI showed lower FC in a hyper-synchronized anterior network and a posterior network. |
Lopez-Sanz et al. (2017) [168] | Self-reported cognitive concerns, older than 60 | MEG and T1 MRI | Cross-sectional | NC: n = 63 (70.7 ± 4.5) SCD: n = 55 (71.0 ± 5.0) MCI: n = 69 (71.9 ± 4.2) | SCD showed decreased clustering and transitivity in theta and beta bands but increased modularity and transitivity in alpha band. |
Maestu et al. (2011) [176] | Patient stating that their memory function has deteriorated compared to earlier stages in life | MEG | Cross-sectional | NC: n = 6 (72 ± 8) SCD: n = 12 (72 ± 6) MCI: n = 21 (75 ± 3) | The SCD showed higher activation than the control group in posterior ventral regions and in the dorsal pathway. MCI patients showed higher activation than the control group in the posterior part of the ventral pathway. |
Prichep et al., (2006) [174] | Memory clinic consultation | EEG | Cross-sectional | Nondecliners: n = 17 (70.0 ± 4.1) Decliners: n =27 (73.5 ± 4.9) | Decliners showed increase in theta power. |
Multimodal neuroimaging studies
Authors | Definition of SCD | Modality | Design | Sample (mean age ± SD) | Main findings |
---|---|---|---|---|---|
Buckley et al. (2017) [190] | SCD composite questions | PiB-PET FTP-PET | Cross-sectional | All: n = 133 (75.9±7.0) Aß negative: n = 94 (74.9±7.2) Aß positive: n = 39 (78.4±5.7) | Greater SCD relate to increased entorhinal tau burden and Aß burden |
1 binary question | PiB-PET MRI | Cross-sectional | NC: n = 45 (74.9±7.1) SCI: n = 49 (73.9±7.2) MCI:n = 34 (75.4±7.2) AD: n = 35 (75.1±7.9) | Relation between global and regional atrophy and Aβ-amyloid load in SCI individuals but not in MCI or AD dementia | |
1 binary question | PiB-PET MRI | Cross-sectional | HC-: n = 32 (73.1±7.1) HC+: n = 13 (78.9±5.5) SCI-: n = 30 (72.1±7.1) SCI+: n = 19 (76.7±6.5) MCI+: n = 22 (75.8±7.1) AD+: n = 34 (75±7.9) | Larger temporal gray matter volume in HC with high amyloid load; gray matter atrophy in SCI with high amyloid load and MCI compared to HC | |
2 binary questions | 18F-florbetapir PET Rs-fMRI | Cross-sectional | Overall: n = 267 (75.8±3.5) ApoE ɛ4 noncarriers: n = 192 (75.7±3.6) ApoE ɛ4 carriers: n = 53 (76.1±3.6) | Higher SUVR values related to lower posterior basal forebrain RSFC in the hippocampus and the thalamus, impacted by sex and ApoE genotype | |
2 binary questions | 18F-florbetapir PET Rs-fMRI | Cross-sectional | All: n = 224 (75.5±3.4) ApoE ɛ4 noncarriers: n = 180 (75.5±3.4) ApoE ɛ4 carriers: n = 44 (75.6±3.5) | DMN changes in frontal and posterior areas and right hippocampus. No impact of brain amyloid load status on longitudinal RSFC. | |
Eliassen et al. (2017) [193] | Cognitive complaints | FDG-PET MRI | Cross-sectional | aMCI: n = 53(61.9±7.8) naMCI: n = 27(60.7±7.8) SCD: n = 38(59±8.3) | Lower cortical glucose metabolism in aMCI than SCD and controls. Thinner entorhinal cortex in SCD and aMCI |
Ferreira et al. (2017) [183] | 1 binary question | PiB-PET MRI | Cross-sectional | HC-like SMD: n = 75 (72.5±6.8) AD-like SMD: n = 11 (75.3±8.8) | The disease severity index identified eleven (13%) SCD with AD-like pattern of brain atrophy, who show lower cognitive performance, higher amyloid deposition, and worse clinical progression |
Gaubert et al. (2019) [189] | Memory complaint | 18F-florbetapir PET EEG | Cross-sectional | All: n = 314 (76.07±3.47) A-N-: n = 175 (75.62±3.39) A+N-: n = 63 (76.81±3.19) A+N+: n = 25 (76.88±4.01) | EEG metrics of fronto-central regions correlate with neurodegeneration. A U-shape or inverted U-shape relationships between amyloid burden and EEG metrics in neurodegeneration positive subjects |
Kramberger et al. (2017) [188] | Memory clinic consultation | EEG MRI | Cross-sectional | SCI: n = 194 (57.7±7.5) MCI: n = 141 (61.7±8.3) AD: n = 58 (63.6±7.0) | WMLs and medial temporal atrophy relate to slower BA in all diagnoses |
Kuhn et al. (2019) [192] | Composite of 10 questions CDS | 18F-florbetapir PET FDG-PET MRI | Longitudinal (15-43 months) | HC: n=28 (72.25±6.33) SCD-community: n = 23 (71.70±6.60) SCD-clinic: n = 27 (68.30±7,99) | Higher self-reported SCD relate to lower gray matter volume and higher anxiety in SCD-community, to greater informant-reported SCD in SCD-clinic and to lower glucose metabolism in both SCD groups |
Li et al. (2018) [187] | CCI | 18F-florbetapir PET MRI | Cross-sectional | NC: n = 40 (75.10±5.39) SMC: n = 44 (73.78±5.81) | Higher DC in the bilateral hippocampus and left fusiform gyrus and lower DC in inferior parietal in SMC. DC in bilateral hippocampus and left fusiform relate to total tau and phosphorylated tau, but not to amyloid deposition |
Scheef et al. (2012) [59] | Memory clinic consultation 2 binary questions | FDG-PET MRI | Cross-sectional | Controls: n = 56 (66.4±7.2) SMI: n = 31 (67.6±6.2) | Hypometabolism in right precuneus and hypermetabolism in right medial temporal and reduced gray matter volume in hippocampus in SMI group. Longitudinal memory decline relates to reduced glucose metabolism in right precuneus in SMI |
Shokouhi et al. (2019) [191] | E-Cog | 18F-flortaucipir PET 18F-florbetapir PET | Cross-sectional | All: n = 86 (78±8) | Tau pathology predict everyday planning in SCD, and amyloid pathology relate to everyday organization and memory in SCD |
Teipel et al. (2018) [178] | 2 binary questions | 18F-florbetapir PET MRI EEG | Cross-sectional | Amyloid negative: n = 63 (75.9±3.5) Amyloid positive: n = 255 (76.7±3.5) | No significant relationship between amyloid load and phase-lag index in any frequency band |
Teipel et al. (2017) [182] | 2 binary questions | 18F-florbetapir PET MRI | Cross-sectional | All: n = 318 (76.1±3.5) | Association between amyloid uptake and reduced gray matter structural integrity and poorer objective cognitive performance |
Ten Kate et al. (2018) [101] | 2 binary questions | 18F-florbetapir PET MRI | Cross-sectional | All: n=318(76 74±78) Amyloid-: n = 230 (76 73±78) Amyloid+: n = 88 (77 75±79) | Association between higher global SUVR and lower clustering, and small world values in orbito-and dorsolateral frontal and parietooccipital regions. |
Wirth et al. (2018) [184] | Memory clinic consultation | 18F-florbetapir PET MRI FDG-PET | Cross-sectional | HC: n=41 (66.1 ±7.7) ApoE ɛ4+: n = 17 (63.9±8.6) SCD: n=16 (68.9±7.3) MCI: n=30 (73.4±7.2) AD: n=22 (68.7±9.4) | (1) in medial-temporal regions, local gray matter volume reduction exceeded hypometabolism, (2) in temporoparietal regions, hypometabolism predominated over gray matter volume reduction, and (3) in frontal regions, Aβ deposition exceeded gray matter volume reduction and hypometabolism. Three distinct biomarker patterns in MCI, only pattern 1 in SCD, only pattern 3 in ApoE ɛ4 carriers |
Yasuno et al. (2015) [113] | EMC | PiB-PET MRI | Cross-sectional | nSCI: n = 30 (72.2±4.8) SCI: n = 23 (69.6±8.0) | Reduced FC in cortical midline structure in SCI. reduced WM connections relate to reduced FC. No amyloid deposition in SCI |