3 J. MAGN. RESON. IMAGING 2017;45:1335-1342.

No abstract

BackgroundIndividuals with subjective memory complaints (SMC) feature a higher risk of cognitive decline and clinical progression of Alzheimer’s disease (AD). However, the pathological mechanism underlying SMC remains unclear. We aimed to assess the intrinsic connectivity network and its relationship with AD-related pathologies in SMC individuals.MethodsWe included 44 SMC individuals and 40 normal controls who underwent both resting-state functional MRI and positron emission tomography (PET). Based on graph theory approaches, we detected local and global functional connectivity across the whole brain by using degree centrality (DC) and eigenvector centrality (EC) respectively. Additionally, we analyzed amyloid deposition and tauopathy via florbetapir-PET imaging and cerebrospinal fluid (CSF) data. The voxel-wise two-sample T-test analysis was used to examine between-group differences in the intrinsic functional network and cerebral amyloid deposition. Then, we correlated these network metrics with pathological results.ResultsThe SMC individuals showed higher DC in the bilateral hippocampus (HP) and left fusiform gyrus and lower DC in the inferior parietal region than controls. Across all subjects, the DC of the bilateral HP and left fusiform gyrus was positively associated with total tau and phosphorylated tau181. However, no significant between-group difference existed in EC and cerebral amyloid deposition.ConclusionWe found impaired local, but not global, intrinsic connectivity networks in SMC individuals. Given the relationships between DC value and tau level, we hypothesized that functional changes in SMC individuals might relate to pathological biomarkers.Electronic supplementary materialThe online version of this article (10.1186/s40035-018-0130-z) contains supplementary material, which is available to authorized users.

ObjectiveIt remains unclear if and how the interactions between APOE genotypes and cerebral small-vessel diseases (CSVD) lead to cognitive decline in the long term. Based on ADNI cohort, this longitudinal study aimed to clarify the potential relationship among APOE genotype, CSVD and cognition by integrating multi-level data.MethodThere were 135 healthy elderly (including ε2, ε4 allele carriers and ε3 homozygotes) who had completed two years’ follow-up. MRI markers of CSVD, including white matter hyperintensities (WMH), dilated perivascular space (dPVS), microbleeds and lacune, were assessed. Besides, neuropathological factors including Alzheimer's disease-related pathology measured by CSF and PiB-PET were assessed. Repeated measurements ANOVAs were performed to test impact of different APOE genotypes on CSVD.ResultsWe found that APOE ε4 carriers had significantly more frontal WMH burden and basal ganglia dPVS at baseline and faster progression of frontal WMH burden during follow-up. Furthermore, our results showed that APOE ε4 carriers had significantly decreased Aβ1-42 level, and its level was negatively related with baseline and progressive total WMH burden. Then, general linear modals indicated interaction between basal frontal WMH burden and ε4 allele was related with declining trend of cognition.ConclusionOur findings suggested APOE ε4 allele was associated with increased Aβ deposition, which may lead to the formation and progression of WMH, especially in frontal lobe. Besides, interaction between the increased frontal WMH burden and ε4 allele can exert long-term detrimental effects on individual's trajectory of cognition.

Alzheimer's disease (AD) has a long neuropathological accumulation phase before the onset of dementia. Such AD neuropathological deposition between neurons impairs the synaptic communication, resulting in networks disorganization. Our study aimed to explore the evolution patterns of gray matter structural covariance networks (SCNs) along AD continuum. Based on the AT(N) (i.e., Amyloid/Tau/Neurodegeneration) pathological classification system, we classified subjects into four groups using cerebrospinal fluid amyloid-beta 1–42 (A) and phosphorylated tau protein 181 (T). We identified 101 subjects with normal AD biomarkers (A-T-), 40 subjects with Alzheimer's pathologic change (A + T−), 101 subjects with biological AD (A + T+) and 91 AD with dementia (demented subjects with A + T+). We used four regions of interest to anchor default mode network (DMN, medial temporal subsystem and midline core subsystem), salience network (SN) and executive control network (ECN). Finally, we used a multi-regression model-based linear-interaction analysis to assess the SCN changes. Along the disease progression, DMN and SN showed increased structural association at the early stage while decreased structural association at the late stage. Moreover, ECN showed progressively increased structural association as AD neuropathological profiles progress. In conclusion, this study found the dynamic trajectory of SCNs changes along the AD continuum and support the network disconnection hypothesis underlying AD neuropathological progression. Further, SCN may potentially serve as an effective AD biomarker.