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Table 5 Summary of multimodal 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
Buckley et al. (2017) [190] SCD composite questions PiB-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
Chetelat et al. (2010) [180, 181] 1 binary question PiB-PET
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
Che ́telat et al. (2010) [180, 181] 1 binary question PiB-PET
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
Chiesa et al. (2019) [140, 185] 2 binary questions 18F-florbetapir PET
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
Chiesa et al. (2019) [140, 185] 2 binary questions 18F-florbetapir PET
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
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
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
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
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
18F-florbetapir PET
(15-43 months)
HC: n=28 (72.25±6.33)
SCD-community: n = 23 (71.70±6.60)
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
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
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
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
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
Cross-sectional All: n=318(76 74±78)
n = 230 (76 73±78)
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
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
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
  1. SCC Subjective cognitive complaints, ND Neurodegeneration, FDG 18F-Fluorodeoxyglucose, EEG Electroencephalography, WM White matter, SMD Subjective memory decline, FTP Flortaucipir, SCD Subjective cognitive decline, CDR Clinical dementia rating, E-Cog Everyday Cognition Scale, 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, IP Isoprostane, SUVR Standardized uptake value ratio, SCI Subjective cognitive impairment, MCI Mild cognitive impairment, aMCI Amnestic MCI, naMCI Non-amnestic MCI, NC Normal control, PET Positron emission tomography, PiB Pittsburgh compound B. ADNI: Alzheimer’s Disease Neuroimaging Initiative, MRI Magnetic resonance imaging, WMLs White matter lesions, rs-fMRI Resting-state functional MRI, DMN Default mode network, RSFC Resting-state functional connectivity, FC Functional connectivity, DC Degree centrality