Alterations in Gut Microbiota and Their Correlation with Brain Beta-Amyloid Burden Measured by 18F-Florbetaben PET in Mild Cognitive Impairment Due to Alzheimer's Disease.

(1) Background: This study investigated changes in the gut microbial composition of individuals with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and their relationship with positron emission tomography (PET) amyloid accumulation. (2) Methods: In total, 17 cognitively normal individuals without amyloid-beta (Aß) accumulation (Aß-NC) and 24 with Aß-positive mild cognitive impairment (Aß+MCI) who underwent 18F-florbetaben PET and fecal bacterial 16S ribosomal RNA gene sequencing were enrolled. The taxonomic compositions of the Aß-NC and Aß+MCI groups were compared. The abundance of taxa was correlated with the standardized uptake value ratio (SUVR), using generalized linear models. (3) Results: There were significant differences in microbiome richness (ACE, p = 0.034 and Chao1, p = 0.024), alpha diversity (Shannon, p = 0.039), and beta diversity (Bray-Curtis, p = 0.018 and Generalized UniFrac, p = 0.034) between the Aß-NC and Aß+MCI groups. The global SUVR was positively correlated with the genus Intestinibacter (q = 0.006) and negatively correlated with the genera Roseburia (q = 0.008) and Agathobaculum (q = 0.029). (4) Conclusions: In this study, we identified significant changes in the gut microbiota composition that occur in individuals with MCI due to AD. In particular, the correlation analysis results between PET amyloid burden and gut microbial abundance showed that amyloid deposition is associated with a reduction in specific taxa involved in butyrate production.

Predicting superagers by machine learning classification based on the functional brain connectome using resting-state functional magnetic resonance imaging.

Superagers are defined as older adults who have youthful memory performance comparable to that of middle-aged adults. Classifying superagers based on the brain connectome using machine learning modeling can provide important insights on the physiology underlying successful aging. We aimed to investigate the unique patterns of functional brain connectome of superagers and develop predictive models to differentiate superagers from typical agers based on machine learning methods. We obtained resting-state functional magnetic resonance imaging (rsfMRI) data and cognitive measures from 32 superagers and 58 typical agers. The accuracies of three machine learning methods including the linear support vector machine classifier (SV), the random forest classifier (RF), and the logistic regression classifier (LR) in predicting superagers were comparable (SV = 0.944, RF = 0.944, LR = 0.944); however, RF achieved the highest area under the curve (AUC; 0.979). An ensemble learning method combining the three classifiers achieved the highest AUC (0.986). The most discriminative nodes for predicting superagers encompassed areas in the precuneus; posterior cingulate gyrus; insular cortex; and superior, middle, and inferior frontal gyrus, which were located in default, salient, and multiple-demand networks. Thus, rsfMRI data can provide high accuracy for predicting superagers, thereby capturing and describing the unique characteristics of their functional brain connectome.

The Moderating Role of Sleep Quality on the Association between Neuroticism and Frontal Executive Function in Older Adults.

OBJECTIVE/BACKGROUND: Personality traits are regarded as risk factors for cognitive impairment in older adults, while sleep disturbance and physical inactivity are also considered as modifiable risk factors. Therefore, it could be beneficial to investigate the effects of those modifiable risk factors on the relationship between personality traits and cognitive functions, to prepare appropriate strategies for mitigating cognitive impairment. PARTICIPANTS: A total of 155 cognitively unimpaired older adults were included. METHODS: All participants underwent cognitive function tests using the Seoul Neuropsychological Screening Battery and examinations for personality traits using the Big Five Inventory. Individual physical activity and sleep quality were assessed using the International Physical Activity Questionnaire and Pittsburgh Sleep Quality Index, respectively. A hierarchical linear multiple regression analysis was performed to demonstrate the direct association between personality traits and cognitive functions, and the multiple moderator analysis was used to analyze the moderating effects of lifestyle factors on this association. RESULTS: Among the five personality traits, only neuroticism was negatively associated with the frontal executive and visuospatial functions after controlling age, sex, and years of education. Interestingly, the negative relationship between neuroticism and frontal executive function was alleviated in older adults with higher sleep quality. CONCLUSIONS: Our findings demonstrated that higher sleep quality has significant moderating effects on the negative association between neuroticism and frontal executive functions in older adults, which suggests intervention for improving sleep quality such as cognitive behavioral therapy can be considered in older adults who have personality traits associated with a high risk of cognitive impairment.

Aberrantly higher functional connectivity in the salience network is associated with transient global amnesia.

Triple intrinsic brain networks including the salience network (SN), default mode network (DMN), and central executive network (CEN), are known to be important in human cognition. Therefore, investigating those intrinsic brain networks in transient global amnesia (TGA) may offer novel insight useful for the pathophysiology of TGA. Fifty TGA patients underwent the resting state functional magnetic resonance imaging (rsfMRI) within 24 h, at 72 h, and 3 months after TGA onset. Twenty-five age, gender matched controls also underwent rsfMRI. Within 24 h of TGA onset, TGA patients showed greater functional connectivity in the SN and lower functional connectivity in the DMN, while relatively preserved functional connectivity was observed in the CEN. Interestingly, TGA patients continued to show decreased connectivity in the DMN, while no alterations were shown in the SN 72 h after illness onset. Three months after TGA onset, alterations of functional connectivity in the SN or the DMN were normalized. Our findings suggest that TGA is associated with transient greater functional connectivity in the SN and lower connectivity in the DMN.

White Matter Integrity Is Associated With the Amount of Physical Activity in Older Adults With Super-aging.

Previous studies have introduced the concept of "SuperAgers," defined as older adults with youthful memory performance associated with the increased cortical thickness of the anterior cingulate cortex. Given that age-related structural brain changes are observed earlier in the white matter (WM) than in the cortical areas, we investigated whether WM integrity is different between the SuperAgers (SA) and typical agers (TA) and whether it is associated with superior memory performance as well as a healthy lifestyle. A total of 35 SA and 55 TA were recruited for this study. Further, 3.0-T magnetic resonance imaging (MRI), neuropsychological tests, and lifestyle factors related to cognitive function, such as physical activity and duration of sleep, were evaluated in all participants. SA was defined as individuals demonstrating the youthful performance of verbal and visual memory, as measured by the Seoul Verbal Learning Test (SVLT) and the Rey-Osterrieth Complex Figure Test (RCFT), respectively. Tract-based spatial statistics (TBSS) analysis was used to compare the diffusion values such as fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) between the SA and TA. SA exhibited better performance in memory, attention, visuospatial, and frontal executive functions than the TA did. SA also exhibited greater amounts of physical activity than the TA did. As compared to TA, SA demonstrated higher FA with lower MD, RD, and AD in the corpus callosum and higher FA and lower RD in the right superior longitudinal fasciculus (SLF), which is significantly associated with memory function. Interestingly, FA values of the body of corpus callosum were correlated with the amount of physical activity. Our findings suggest that WM integrity of the corpus callosum is associated with superior memory function and a higher level of physical activities in SA compared to TA.

Four-Week, Home-Based, Robot Cognitive Intervention for Patients with Mild Cognitive Impairment: a Pilot Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Previous studies suggest that cognitive intervention can mitigate the development of dementia in patients with mild cognitive impairment (MCI). However, the previous cognitive intervention was mostly provided as a group session, in which MCI patients sometimes had difficulty in regularly attending sessions or were reluctant to participate in group-based classes. Additionally, experienced instructors for traditional cognitive intervention may be unavailable in some chronic-care facilities or community centers. Considering these reasons, we have developed 5 programs for home-based cognitive intervention using a personal robot for MCI patients. In this preliminary study, we aimed to demonstrate the effects of our newly developed home-based cognitive intervention with robots on cognitive function in MCI patients. METHODS: We conducted a single-blind randomized controlled trial enrolling 46 MCI patients. Participants were randomized into 2 groups: the robot cognitive intervention (robot) (n=24) group and without cognitive intervention (control) (n=22) group. The interventions comprised 60-min sessions per day for 4 weeks. The primary outcome was the change in cognitive function measured using the Cambridge Neuropsychological Test Automated Battery. RESULTS: There were no significant baseline demographic or clinical differences between the robot and control groups. After the 4-week cognitive intervention, the robot group showed greater improvement in working memory than did the control group. CONCLUSIONS: Our home-based cognitive intervention with a personal robot improved the working memory in MCI patients. Further studies with larger samples and longer study periods are required to demonstrate the effects of these programs in other cognitive domains in MCI patients.

Alterations in structural rich-club connectivity of the precuneus are associated with depressive symptoms among individuals with subjective memory complaints.

The association between subjective memory complaints (SMCs) and depressive symptoms has been widely reported and both have been regarded as risk factors for dementia, such as Alzheimer's disease (AD). Although SMCs arise as early as in middle age, the exact neural correlates of comorbid depressive symptoms among individuals who are middle-aged and with SMCs have not yet been well investigated. Because rich-club organization of the brain plays a key role in the pathophysiology of various neuropsychiatric disorders, the investigation of rich club organization may provide insight regarding the neurobiological mechanisms of depressive symptoms in SMCs. In the current study, we compared the rich-club organization in the structural brain connectivity between individuals who have SMCs along with depressive symptoms (SMCD) and individuals with SMCs but without depressive symptoms (SMCO). A total of 53 individuals with SMCD and 91 individuals with SMCO participated in the study. For all participants, high-resolution, T1-weighted images and diffusion tensor images were obtained, and the network analysis was performed. Individuals with SMCD had lower connectivity strength between the precuneus and other rich-club nodes than those with SMCO, which was significant after adjusting for potential confounders. Our findings suggest that disruptions of rich-club connectivity strength of the precuenus are associated with depressive symptoms in middle-aged individuals with SMCs. Given that the precuneus is one of the commonly affected regions in the early stages of AD, our findings may imply that the concomitant depressive symptoms in middle-aged individuals with SMCs could reflect structural alterations related to AD.

Recovery from Posttraumatic Stress Requires Dynamic and Sequential Shifts in Amygdalar Connectivities.

The neural mechanisms underlying the development and maintenance of posttraumatic stress disorder (PTSD) have long been studied. However, little is known about the neural correlates of the recovery process from PTSD. A 5-year longitudinal study was conducted to investigate the trajectory of structural connectivities of the amygdala in disaster survivors with PTSD. Thirty disaster survivors, who were diagnosed with PTSD, and 29 healthy individuals, who were not exposed to trauma, underwent three waves of assessments including neuroimaging scanning over a 5-year period from the time of the disaster at approximately 1.3-year intervals. All disaster survivors showed significant improvements in PTSD symptoms over time. Using diffusion tensor imaging analysis, a 5-year trajectory of amygdalar structural connectivities with key brain regions was assessed. The amygdala-insula connection was initially strengthened and then normalized during recovery, while the amygdala-prefrontal cortex (PFC) connection was at first unaffected, then strengthened, and eventually normalized. The lower tract strength of the amygdala-thalamus connection normalized during recovery, while that of amygdala-hippocampus connection remained low. The greater amygdala-PFC connectivity was associated with less PTSD symptom severity. The present longitudinal study revealed that recovery from PTSD parallels dynamic and sequential shifts in amygdalar connectivities with multiple brain regions, suggesting the expanded view of fear circuitry including the insula and thalamus, beyond the traditional model which primarily involves the amygdala, PFC, and hippocampus.

Subregional Shape Alterations in the Amygdala in Patients with Panic Disorder.

BACKGROUND: The amygdala has been known to play a pivotal role in mediating fear-related responses including panic attacks. Given the functionally distinct role of the amygdalar subregions, morphometric measurements of the amygdala may point to the pathophysiological mechanisms underlying panic disorder. The current study aimed to determine the global and local morphometric alterations of the amygdala related to panic disorder. METHODS: Volumetric and surface-based morphometric approach to high-resolution three-dimensional T1-weighted images was used to examine the structural variations of the amygdala, with respect to extent and location, in 23 patients with panic disorder and 31 matched healthy individuals. RESULTS: There were no significant differences in bilateral amygdalar volumes between patients with panic disorder and healthy individuals despite a trend-level right amygdalar volume reduction related to panic disorder (right, ß = -0.23, p = 0.09, Cohen's d = 0.51; left, ß = -0.18, p = 0.19, Cohen's d = 0.45). Amygdalar subregions were localized into three groups including the superficial, centromedial, and laterobasal groups based on the cytoarchitectonically defined probability map. Surface-based morphometric analysis revealed shape alterations in the laterobasal and centromedial groups of the right amygdala in patients with panic disorder (false discovery rate corrected p < 0.05). CONCLUSIONS: The current findings suggest that subregion-specific shape alterations in the right amygdala may be involved in the development and maintenance of panic disorder, which may be attributed to the cause or effects of amygdalar hyperactivation.

Effects of Ganglioside on Working Memory and the Default Mode Network in Individuals with Subjective Cognitive Impairment: A Randomized Controlled Trial.

This randomized, double-blind, placebo-controlled trial examined whether the administration of ganglioside, an active ingredient of deer bone extract, can improve working memory performance by increasing gray matter volume and functional connectivity in the default mode network (DMN) in individuals with subjective cognitive impairment. Seventy-five individuals with subjective cognitive impairment were chosen to receive either ganglioside (330[Formula: see text][Formula: see text]g/day or 660[Formula: see text][Formula: see text]g/day) or a placebo for 8 weeks. Changes in working memory performance with treatment of either ganglioside or placebo were assessed as cognitive outcome measures. Using voxel-based morphometry and functional connectivity analyses, changes in gray matter volume and functional connectivity in the DMN were also assessed as brain outcome measures. Improvement in working memory performance was greater in the ganglioside group than in the placebo group. The ganglioside group, relative to the placebo group, showed greater increases in gray matter volume and functional connectivity in the DMN. A significant relationship between increased functional connectivity of the precuneus and improved working memory performance was observed in the ganglioside group. The current findings suggest that ganglioside has cognitive-enhancing effects in individuals with subjective cognitive impairment. Ganglioside-induced increases in gray matter volume and functional connectivity in the DMN may partly be responsible for the potential nootropic effects of ganglioside. The clinical trial was registered with ClinicalTrials.gov (identifier: NCT02379481).