Xuanyu Li

Abnormal Resting-State Functional Connectivity Strength in Mild Cognitive Impairment and Its Conversion to Alzheimer’s Disease

Individuals diagnosed with mild cognitive impairment (MCI) are at high risk of transition to Alzheimers disease (AD). However, little is known about functional characteristics of the conversion from MCI to AD. Resting-state functional magnetic resonance imaging was performed in 25 AD patients, 31 MCI patients, and 42 well-matched normal controls at baseline. Twenty-one of the 31 MCI patients converted to AD at approximately 24 months of follow-up. Functional connectivity strength (FCS) and seed-based functional connectivity analyses were used to assess the functional differences among the groups. Compared to controls, subjects with MCI and AD showed decreased FCS in the default-mode network and the occipital cortex. Importantly, the FCS of the left angular gyrus and middle occipital gyrus was significantly lower in MCI-converters as compared with MCI-nonconverters. Significantly decreased functional connectivity was found in MCI-converters compared to nonconverters between the left angular gyrus and bilateral inferior parietal lobules, dorsolateral prefrontal and lateral temporal cortices, and the left middle occipital gyrus and right middle occipital gyri. We demonstrated gradual but progressive functional changes during a median 2-year interval in patients converting from MCI to AD, which might serve as early indicators for the dysfunction and progression in the early stage of AD.

White matter degeneration in subjective cognitive decline: a diffusion tensor imaging study

Subjective cognitive decline (SCD) may be an at-risk stage of Alzheimers disease (AD) occurring prior to amnestic mild cognitive impairment (aMCI). To examine white matter (WM) defects in SCD, diffusion images from 27 SCD (age=65.3±8.0), 35 aMCI (age=69.2±8.6) and 25 AD patients (age=68.3±9.4) and 37 normal controls (NC) (age=65.1±6.8) were compared using Tract-Based Spatial Statistics (TBSS). WM impairments common to the three patient groups were extracted, and fractional anisotropy (FA) values were averaged in each group. As compared to NC subjects, SCD patients displayed widespread WM alterations represented by decreased FA (p<0.05), increased mean diffusivity (MD; p<0.05), and increased radial diffusivity (RD; p<0.05). In addition, localized WM alterations showed increased axial diffusivity (AxD; p<0.05) similar to what was observed in aMCI and AD patients (p<0.05). In the shared WM impairment tracts, SCD patients had FA values between the NC group and the other two patient groups. In the NC and SCD groups, the AVLT-delayed recall score correlated with higher AxD (r=−0.333, p=0.045), MD (r=−0.351, p=0.03) and RD (r=−0.353, p=0.025). In both the aMCI and AD groups the diffusion parameters were highly correlated with cognitive scores. Our study suggests that SCD patients present with widespread WM changes, which may contribute to the early memory decline they experience.

Abnormal organization of white matter networks in patients with subjective cognitive decline and mild cognitive impairment

Network analysis has been widely used in studying Alzheimers disease (AD). However, how the white matter network changes in cognitive impaired patients with subjective cognitive decline (SCD) (a symptom emerging during early stage of AD) and amnestic mild cognitive impairment (aMCI) (a pre-dementia stage of AD) is still unclear. Here, structural networks were constructed respectively based on FA and FN for 36 normal controls, 21 SCD patients, and 33 aMCI patients by diffusion tensor imaging and graph theory. Significantly lower efficiency was found in aMCI patients than normal controls (NC). Though not significant, the values in those with SCD were intermediate between aMCI and NC. In addition, our results showed significantly altered betweenness centrality located in right precuneus, calcarine, putamen, and left anterior cingulate in aMCI patients. Furthermore, association was found between network metrics and cognitive impairment. Our study suggests that the structural network properties might be preserved in SCD stage and disrupted in aMCI stage, which may provide novel insights into pathological mechanisms of AD.

Decreased resting-state brain signal complexity in patients with mild cognitive impairment and Alzheimer’s disease: a multi-scale entropy analysis

Multiscale entropy (MSE) analysis is a novel entropy-based analysis method for quantifying the complexity of dynamic neural signals and physiological systems across multiple temporal scales. This approach may assist in elucidating the pathophysiologic mechanisms of amnestic mild cognitive impairment (aMCI) and Alzheimers disease (AD). Using resting-state fNIRS imaging, we recorded spontaneous brain activity from 31 healthy controls (HC), 27 patients with aMCI, and 24 patients with AD. The quantitative analysis of MSE revealed that reduced brain signal complexity in AD patients in several networks, namely, the default, frontoparietal, ventral and dorsal attention networks. For the default and ventral attention networks, the MSE values also showed significant positive correlations with cognitive performances. These findings demonstrated that the MSE-based analysis method could serve as a novel tool for fNIRS study in characterizing and understanding the complexity of abnormal cortical signals in AD cohorts.

INTRINSIC BRAIN NETWORKS OF COGNITIVE COMPONENTS IN SUBJECTIVE COGNITIVE DECLINE

unspecific brain activity. Secondly, a mixed design allows for contrasts of sustained and transient activity [1]. Thirdly, a subsequent recognition test allows for contrasts between remembered versus forgotten items, known as encoding success activity (ESA). Results: Pilot data in 60 participants (mean age 24.2 years, 36 female) showed excellent recognition memory (d’ 1⁄4 1.19, SE 1⁄4 0.05). In the auditory and visual cortex, we found sensory-specific ESA. In both sensory regions, positive ESA (remembered > forgotten) was driven by transient activations that coincided with sustained activity. In the hippocampus and default-network, we found sensoryunspecific ESA. In the hippocampus, positive ESA was driven by transient deactivations that coincided with sustained activity. In the default-network, negative ESA (forgotten > remembered) was driven by transient activations that coincided with sustained deactivations. Conclusions:These results demonstrate the feasibility to map multisensory and memory-related fMRI activity in a largescale population study. Our findings also expose some issues regarding the ambiguity of the fMRI baseline [2]. Within our mixed design, transient ESA (remembered vs. forgotten) was relatively independent from sustained activity (task vs. rest). Thus, future studies can use our paradigm to clarify the influences of age and Alzheimer’s pathology on both sustained and transient activity. [1] Visscher KM, et al. Mixed blocked/event-related designs separate transient and sustained activity in fMRI. NeuroImage 2003;19:1694–708 [2] Stark CE, Squire LR. When zero is not zero: the problem of ambiguous baseline conditions in fMRI. PNAS, 2001;98:12760–6.

ABNORMAL BRAIN CONNECTIVITY DYNAMICS AND BRAIN ACTIVITY STATES IN ALZHEIMER’S DISEASE

infarcts were detected (12 patients (13%); 20 cavitated, 1 non-cavitated; mean size 5.2mm), compared to 48 primary care patients not selected on disease status (1 patient (2%); 1 cavitated; p1⁄40.031; Figure 1). Conclusions: We established reliable imaging criteria for the detection of small infarcts in the caudate nucleus on 7t MRI that can be used in future studies to provide new insights into the pathophysiology of CSVD.

HOW DOES WHITE MATTER CONNECTIVITY DIFFER BETWEEN VASCULAR AND DEGENERATIVE PRE-DEMENTIA?

tients (76% in AD, 75% in FTD, 50% in DLB, and 89% in Others). Among 29 patients with negative [C]PiB-PET scan, 11 patients were evaluated as even not having any progressive neurological disorders and the result lead to drastic change of prognostic view. Conclusions: [C]PiB-PET imaging has high clinical impact on the diagnosis of young onset neurodegenerative dementias. Further studies are required to evaluate the total impact of amyloid imaging in young onset dementias not only on the medical diagnosis but also on social issues such as occupational and familial activities.

DIFFUSION TENSOR IMAGING STUDY IN THE DETECTION OF WHITE MATTER DEGENERATION IN SUBJECTIVE COGNITIVE DECLINE

Background: Subjective cognitive decline (SCD) refers to the selfexperiencedworsening of the cognitive capacity in elderlies,who still perform within normal range on standardized neuropsychological tests (Jessen et al., 2014). Abnormal functional connectivity within default mode network (DMN), which is important for many higher cognitive functions such as episodicmemory and self-referential process, has been observed inSCDbyusing the resting state fMRI.DMN can be further segregated into several sub-networks. It is unclear, whether the functional connectivity within these sub-networks is impaired in the SCD subjects. Methods: 17 SCD subjects and 28 healthy controls (HC) underwent the standardized neuropsychological tests and the resting state fMRImeasurements. The preprocessing of the fMRI images was accomplished by SPM12 by using standard procedure including DARTEL normalization and field map correction. Then, the decomposed independent components (ICs) corresponding to all interested DMN sub-networks of a particular subject were extracted by using a spatial constrained independent component analysis (ICA) with the predefined spatial references of the DMN sub-networks. Group differences between the SCD and HC subjects in each individual IC were carried out by using the two-sample t tests implemented in SPM12. Results: Both groups were not different in the demographic data and neuropsychological performance. Using the spatial constrained ICA technique, three independent components of DMN subnetworks were extracted for each subject, including the midline core network, the dorsal medial prefrontal subnetwork, and the medial temporal lobe subnetwork. Compared to the HC group, the SCD group showed decreased functional connectivity between the dorsal medial prefrontal subnetwork and the right hippocampus, but an increased functional connectivity between themidline core network and the superiormedial frontal cortex (pFWE<0.05; Figure 1). Conclusions: The finding of decreased functional connectivity within the DMN in the right hippocampus in SCD subjects is consistent with a previous resting state functional connectivity study, andmay indicate subtle disruption of the episodic memory system. SCD subjects showed increased connectivity between the midline core subsystem of DMN network and the superior medial frontal cortex,which is a componentof the self-referential system. This result may correspond to self-awareness of cognitive deficits in the SCD subjects.