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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

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

Chetelat et al. (2010) [180, 181]

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

Che ́telat et al. (2010) [180, 181]

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

Chiesa et al. (2019) [140, 185]

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

Chiesa et al. (2019) [140, 185]

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

  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