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Figure 1.

Resting state network maps.

Standard masks of the eight resting state networks (RSNs) as described in Beckmann et al. (2005) are freely available and were downloaded from http://www.fmrib.ox.ac.uk/analysis/royalsoc8/. Blue regions show brain regions included in the RSNs; the medial-visual system, the lateral-visual, auditory system, sensori-motor system, the default mode network, the executive control network, right dorsal visual system and left dorsal visual system.

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Table 1.

Subject characteristics for early-onset Alzheimer’s disease (AD) patients (disease onset <65 years), late-onset AD patients (disease onset ≥65 years), young (<65 years) - and old (≥65 years) healthy age-matched controls (HC).

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Figure 2.

Lowered functional connectivity in AD patients when compared to age-matched controls.

Upper panel shows lower functional connectivity in early-onset AD patients when compared to ‘young’ age-matched controls. Lower panel shows decreased functional connectivity in late-onset AD patients (EOAD) when compared to ‘old’ age-matched controls. Standard maps of the Resting State Networks (RSNs) are shown in transparent blue. Upper panel: Lower functional connectivity was found in early-onset AD patients when compared to aged-matched young controls within the medial-visual system, lateral-visual system, auditory system, sensory-motor system, default mode network, the executive control network and bilateral dorsal-visual stream. Lower panel: late-onset AD patients (LOAD) show lower functional connectivity when compared to old age-matched controls within the default mode network only. Results are displayed in radiological orientation on standard MNI space (MNI152 2 mm), after correction for multiple comparisons across space (p<0.05). Gender and voxel-wise gray matter maps were used as covariates. Brighter colors represent most significant results. Abbreviations: R = right. L = left.

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Table 2.

MNI-coordinates (MNI 152, 2 mm) of peak voxel and total number of voxels that showed significant lower functional connectivity within the resting-state networks (RSNs) when comparing early-onset AD (EOAD) patients with age-matched young healthy controls (HC), when comparing late-onset AD (LOAD) patients with age-matched old HC and in a direct comparison between early-onset AD and late-onset AD patients.

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Figure 3.

Functional connectivity in early-onset AD patients compared to late-onset AD patients.

Standard maps of the Resting State Networks (RSNs) are shown in transparent blue. Lower functional connectivity was found in early-onset AD (EOAD) patients when compared to late-onset AD (LOAD) patients within the default mode network, the auditory system, the sensory-motor system, and bilateral dorsal visual system. Results are displayed in radiological orientation on standard MNI space (MNI152 2 mm), after correction for multiple comparisons (p<0.05). Gender and voxel-wise gray matter maps were used as covariates. Brighter colors represent most significant results. Abbreviations: R = right. L = left.

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Figure 4.

Gray matter loss.

Regions of decreased gray matter volume in early-onset AD (EOAD) patients when compared to age-matched young controls (A). Regions of decreased gray matter volume in late-onset AD (LOAD) patients when compared to age-matched old controls (B). Regions of decreased gray matter volume in early-onset AD patients when compared to late-onset AD (C). Regions of decreased gray matter volume in late-onset AD patients when compared to early-onset AD (D). Results are corrected for multiple comparisons (p<0.05) and are shown in radiological orientation on standard MNI space (MNI152 2 mm). Brighter colors represent most significant results. R = Right. L = Left.

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Figure 4 Expand

Table 3.

Neuropsychological test performance of early-onset and late-onset Alzheimer’s disease (AD) patients.

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Table 3 Expand

Figure 5.

Significant correlations of functional connectivity with cognition in AD patients.

Scatterplots of significant Spearman correlations across AD patients are shown; mean z-scores representing functional connectivity within the resting state network (RSNs) are displayed on the y-axis. Mean z-scores composing the cognitive domains are displayed on the x-axis. Functional connectivity of the right dorsal visual stream (A) was associated with attention. Functional connectivity of the default mode network (B) was associated with visuo-construction. Black squares represent early-onset (EOAD), white squares represent late-onset AD patients (LOAD). Spearman correlation coefficients (ρ) are reported, with corresponding p-value and number of subjects included in the correlation analysis.

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Table 4.

Spearman correlation coefficients of functional connectivity (mean z-score) within significant clusters within the resting-state network (RSNs) maps with performance on 5 cognitive domains (mean z-score).

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