scholarly journals IN VIVO ASSESSMENT OF AMYLOID AND GLUCOSE SIGNATURES IN SUBJECTIVE COGNITIVE DECLINE SUBJECTS

2021 ◽  
pp. 2140018
Author(s):  
XIAOFENG YU ◽  
ZHILONG ZHU ◽  
SHUZHAN ZHENG ◽  
JIAN JIANG ◽  
JUANJUAN JIANG ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Characteristic Curve ◽  
Standardized Uptake Value ◽  
Brain Regions ◽  
Middle Temporal Gyrus ◽  
Subjective Cognitive Decline ◽  
Middle Temporal ◽  
Main Effect ◽  
Heschl Gyrus

Subjective cognitive decline (SCD), characterized by self-perceived subtle cognitive impairment ahead of the appearance of explicit and measurable cognitive deficits, is regarded as the preclinical manifestation of the pathological change continuum of Alzheimer’s disease (AD). We were committed to exploring the amyloid and glucose metabolic signatures related to imminent brain metabolic changes in SCD subjects. This study included 39 subjects (mean age = 71.9 years; 14 males and 25 females) diagnosed with SCD disease and 39 gender-matched healthy controls (HCs) (mean age = 75.2; 16 males and 23 females) with brain [18F] fluorodeoxyglucose positron emission tomography (PET) images and [18F] florbetapir PET images. The standardized uptake value ratios (SUVRs) of PET images within the regions of interest (ROIs) were calculated. Inter-group SUVR differences were assessed by two-sample [Formula: see text]-testing and receiver operating characteristic curve (ROC) analyses. A generalized linear model (GLM) was employed to evaluate the correlations between amyloid and FDG uptake. Compared with HCs, SCD subjects showed significantly increased amyloid SUVR, as well as significantly increased glucose SUVR in the olfactory, amygdala, thalamus, heschl gyrus, superior and middle temporal gyrus and temporal pole (all [Formula: see text]). The amyloid SUVR of thalamus was found to have a better ROC result (area under the curve (AUC): 0.77, 95% confidence interval (CI): 0.66–0.86) in the HC group, as was the case with the glucose SUVR of the middle temporal gyrus (AUC: 0.83, 95% CI: 0.73–0.91). There were significant positive correlations between amyloid and glucose SUVRs ([Formula: see text]). The amyloid SUVR of the thalamus showed a significantly better main effect (odd ratio [Formula: see text] 2.91, 95% CI: 1.44–6.7, [Formula: see text]), and the glucose SUVR of the heschl gyrus indicated an enhanced main effect (odd ratio [Formula: see text] 5.08, 95% CI: 1.86–18.15, [Formula: see text]). SCD subjects demonstrated significant amyloid accumulation and glucose hypermetabolism in specific brain regions, and amyloid pathology overlapped with regions of glucose abnormality. These findings may advance the understanding of imminent pathological changes in the SCD stage and help to provide clinical guidelines for interventional management.

Difference in Amyloid Load Between Single Memory Domain and Multidomain Subjective Cognitive Decline: A Study from the SILCODE

2021 ◽  
pp. 1-10
Author(s):  
Xiaoqi Wang ◽  
Qiuhui Bi ◽  
Jie Lu ◽  
Piu Chan ◽  
Xiaochen Hu ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Memory Function ◽  
Verbal Learning ◽  
Linear Regression Analysis ◽  
Brain Regions ◽  
Middle Temporal Gyrus ◽  
Subjective Cognitive Decline ◽  
Amyloid Load ◽  
Relationship Of ◽  
The Relationship

Background: Subjective cognitive decline (SCD), an at-risk condition of Alzheimer’s disease (AD), can involve various cognitive domains, such as memory, language, planning, and attention. Objective: We aims to explore the differences in amyloid load between the single memory domain SCD (sd-SCD) and the multidomain SCD (md-SCD) and assess the relationship of amyloid pathology with quantitative SCD scores and objective cognition. Methods: A total of 63 SCD participants from the SILCODE study underwent the clinical evaluation, neuropsychological assessment, and 18F-florbetapir PET scan. Global amyloid standard uptake value ratio (SUVr) was calculated. Additionally, regional amyloid SUVr was quantified in 12 brain regions of interests. A nonparametric rank ANCOVA was used to compare the global and regional amyloid SUVr between the md-SCD (n = 34) and sd-SCD (n = 29) groups. A multiple linear regression analysis was conducted to test the relationship of amyloid SUVr with quantitative SCD scores and objective cognition. Results: Compared with individuals with sd-SCD, individuals with md-SCD had increased global amyloid SUVr (F = 5.033, p = 0.029) and regional amyloid SUVr in the left middle temporal gyrus (F = 12.309, p = 0.001; Bonferroni corrected), after controlling for the effects of age, sex, and education. When pooling all SCD participants together, the increased global amyloid SUVr was related with higher SCD-plus sum scores and lower Auditory Verbal Learning Test-delayed recall scores. Conclusion: According to our findings, individuals with md-SCD showed higher amyloid accumulation than individuals with sd-SCD, suggesting that md-SCD may experience a more advanced stage of SCD. Additionally, increased global amyloid load was predictive of a poorer episodic memory function in SCD individuals.

scholarly journals Subjective Cognitive Decline Modifies the Relationship Between Cerebral Blood Flow and Memory Function in Cognitively Normal Older Adults

2017 ◽  
Vol 24 (3) ◽  
pp. 213-223 ◽  
Author(s):  
Chelsea C. Hays ◽  
Zvinka Z. Zlatar ◽  
Laura Campbell ◽  
M.J. Meloy ◽  
Christina E. Wierenga
Keyword(s):  
Cognitive Decline ◽  
Verbal Memory ◽  
Memory Performance ◽  
Inferior Frontal Gyrus ◽  
Memory Function ◽  
Posterior Cingulate Cortex ◽  
Middle Temporal Gyrus ◽  
Subjective Cognitive Decline ◽  
Cognitively Normal ◽  
Middle Temporal

AbstractObjectives: Subjective cognitive decline (SCD), or self-reported cognitive decline despite normal neuropsychological test performance, is a risk factor for objective cognitive decline and Alzheimer’s disease (AD). While brain mechanisms contributing to SCD are not well defined, studies show associations with vascular risk factors and altered cerebral blood flow (CBF), raising the hypothesis that those with SCD might be experiencing vascular dysregulation, or a disruption in the normal relationship between CBF and cognition. We examined whether the association between CBF and verbal memory performance differs between those with SCD (SCD+) and those without SCD (SCD-). Methods: Linear mixed-effects models were used to investigate whether the voxel-wise relationship between arterial spin labeling (ASL) MRI-measured CBF and verbal memory performance was modified by SCD among a group of 70 cognitively normal older adults (35 SCD+, 35 SCD-; mean age=72) matched on age, gender, and symptoms of depression. Results: Results indicated that the SCD- group exhibited positive associations between verbal memory and CBF within the posterior cingulate cortex, middle temporal gyrus, and inferior frontal gyrus, whereas the SCD+ group displayed negative associations between verbal memory and CBF within the posterior cingulate cortex, middle temporal gyrus, hippocampus, fusiform gyrus, and inferior frontal gyrus. Conclusions: Findings suggest that, while higher CBF is supportive of memory function in those without SCD, higher CBF may no longer support memory function in those presenting with SCD, perhaps reflecting neurovascular dysregulation. (JINS, 2018, 24, 213–223)

scholarly journals Glucose metabolism in the right middle temporal gyrus could be a potential biomarker for subjective cognitive decline: a study of a Han population

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Qiu-Yue Dong ◽  
Tao-Ran Li ◽  
Xue-Yan Jiang ◽  
Xiao-Ni Wang ◽  
Ying Han ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Amyloid Deposition ◽  
Middle Temporal Gyrus ◽  
Subjective Cognitive Decline ◽  
Amyloid Pet ◽  
Middle Temporal ◽  
Potential Biomarker ◽  
Increased Risk ◽  
The Right ◽  
Metabolic Biomarkers

Abstract Introduction Subjective cognitive decline (SCD) represents a cognitively normal state but at an increased risk for developing Alzheimer’s disease (AD). Recognizing the glucose metabolic biomarkers of SCD could facilitate the location of areas with metabolic changes at an ultra-early stage. The objective of this study was to explore glucose metabolic biomarkers of SCD at the region of interest (ROI) level. Methods This study was based on cohorts from two tertiary medical centers, and it was part of the SILCODE project (NCT03370744). Twenty-six normal control (NC) cases and 32 SCD cases were in cohort 1; 36 NCs, 23 cases of SCD, 32 cases of amnestic mild cognitive impairment (aMCIs), 32 cases of AD dementia (ADDs), and 22 cases of dementia with Lewy bodies (DLBs) were in cohort 2. Each subject underwent [18F]fluoro-2-deoxyglucose positron emission tomography (PET) imaging and magnetic resonance imaging (MRI), and subjects from cohort 1 additionally underwent amyloid-PET scanning. The ROI analysis was based on the Anatomical Automatic Labeling (AAL) template; multiple permutation tests and repeated cross-validations were conducted to determine the metabolic differences between NC and SCD cases. In addition, receiver operating characteristic curves were used to evaluate the capabilities of potential glucose metabolic biomarkers in distinguishing different groups. Pearson correlation analysis was also performed to explore the correlation between glucose metabolic biomarkers and neuropsychological scales or amyloid deposition. Results Only the right middle temporal gyrus (RMTG) passed the methodological verification, and its metabolic levels were correlated with the degrees of complaints (R = − 0.239, p = 0.009), depression (R = − 0.200, p = 0.030), and abilities of delayed memory (R = 0.207, p = 0.025), and were weakly correlated with cortical amyloid deposition (R = − 0.246, p = 0.066). Furthermore, RMTG metabolism gradually decreased across the cognitive continuum, and its diagnostic efficiency was comparable (NC vs. ADD, aMCI, or DLB) or even superior (NC vs. SCD) to that of the metabolism of the posterior cingulate cortex or precuneus. Conclusions These findings suggest that the hypometabolism of RMTG could be a typical feature of SCD, and the large-scale hypometabolism in patients with symptomatic stages of AD may start from the RMTG, which gradually progresses starting in the preclinical stage. The specificity of identifying SCD from the perspective of self-perceived symptoms is likely to be increased by the detection of RMTG metabolism.

Changes in synaptic density in the subacute phase after ischemic stroke: A 11C-UCB-J PET/MR study

2021 ◽  
pp. 0271678X2110477
Author(s):  
Laura Michiels ◽  
Nathalie Mertens ◽  
Liselot Thijs ◽  
Ahmed Radwan ◽  
Stefan Sunaert ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Standardized Uptake Value ◽  
Brain Regions ◽  
Asymmetry Index ◽  
Cerebellar Hemisphere ◽  
Future Research ◽  
Stroke Patients ◽  
Synaptic Density ◽  
Positron Emission

Functional alterations after ischemic stroke have been described with Magnetic Resonance Imaging (MRI) and perfusion Positron Emission Tomography (PET), but no data on in vivo synaptic changes exist. Recently, imaging of synaptic density became available by targeting synaptic vesicle protein 2 A, a protein ubiquitously expressed in all presynaptic nerve terminals. We hypothesized that in subacute ischemic stroke loss of synaptic density can be evaluated with 11C-UCB-J PET in the ischemic tissue and that alterations in synaptic density can be present in brain regions beyond the ischemic core. We recruited ischemic stroke patients to undergo 11C-UCB-J PET/MR imaging 21 ± 8 days after stroke onset to investigate regional 11C-UCB-J SUVR (standardized uptake value ratio). There was a decrease (but residual signal) of 11C-UCB-J SUVR within the lesion of 16 stroke patients compared to 40 healthy controls (ratiolesion/controls = 0.67 ± 0.28, p = 0.00023). Moreover, 11C-UCB-J SUVR was lower in the non-lesioned tissue of the affected hemisphere compared to the unaffected hemisphere (ΔSUVR = −0.17, p = 0.0035). The contralesional cerebellar hemisphere showed a lower 11C-UCB-J SUVR compared to the ipsilesional cerebellar hemisphere (ΔSUVR = −0.14, p = 0.0048). In 8 out of 16 patients, the asymmetry index suggested crossed cerebellar diaschisis. Future research is required to longitudinally study these changes in synaptic density and their association with outcome.

scholarly journals Imagining Sounds and Images: Decoding the Contribution of Unimodal and Transmodal Brain Regions to Semantic Retrieval in the Absence of Meaningful Input

2019 ◽  
Vol 31 (11) ◽  
pp. 1599-1616 ◽  
Author(s):  
Charlotte Murphy ◽  
Shirley-Ann Rueschemeyer ◽  
Jonathan Smallwood ◽  
Elizabeth Jefferies
Keyword(s):  
Sensory Information ◽  
Brain Regions ◽  
External Input ◽  
Neural Systems ◽  
Middle Temporal Gyrus ◽  
Connectivity Analysis ◽  
Semantic Retrieval ◽  
Middle Temporal ◽  
Auditory Features

In the absence of sensory information, we can generate meaningful images and sounds from representations in memory. However, it remains unclear which neural systems underpin this process and whether tasks requiring the top–down generation of different kinds of features recruit similar or different neural networks. We asked people to internally generate the visual and auditory features of objects, either in isolation (car, dog) or in specific and complex meaning-based contexts (car/dog race). Using an fMRI decoding approach, in conjunction with functional connectivity analysis, we examined the role of auditory/visual cortex and transmodal brain regions. Conceptual retrieval in the absence of external input recruited sensory and transmodal cortex. The response in transmodal regions—including anterior middle temporal gyrus—was of equal magnitude for visual and auditory features yet nevertheless captured modality information in the pattern of response across voxels. In contrast, sensory regions showed greater activation for modality-relevant features in imagination (even when external inputs did not differ). These data are consistent with the view that transmodal regions support internally generated experiences and that they play a role in integrating perceptual features encoded in memory.

Exploration of the Mechanism Underlying the Association of Incident Microinfarct and Motor Deficit: A Preliminary Functional MRI Study

2021 ◽  
pp. 1-10
Author(s):  
Xiao Luo ◽  
Hui Hong ◽  
Shuyue Wang ◽  
Kaicheng Li ◽  
Qingze Zeng ◽  
...  
Keyword(s):  
Motor Function ◽  
Inferior Frontal Gyrus ◽  
Motor Impairment ◽  
Motor Dysfunction ◽  
Motor Deficit ◽  
Middle Temporal Gyrus ◽  
Eigenvector Centrality ◽  
Middle Temporal ◽  
Mri Study

Background: Cerebral microinfarcts (CMIs) might cause measurable disruption to brain connections and are associated with cognitive decline, but the association between CMIs and motor impairment is still unclear. Objective: To assess the CMIs effect on motor function in vivo and explore the potential neuropathological mechanism based on graph-based network method. Methods: We identified 133 non-demented middle-aged and elderly participants who underwent MRI scanning, cognitive, and motor assessment. The short physical performance battery (SPPB) assessed motor function, including balance, walking speed, and chair stand. We grouped participants into 34 incident CMIs carriers and 99 non-CMIs carriers as controls, depending on diffusion-weighted imaging. Then we assessed the independent CMIs effects on motor function and explored neural mechanisms of CMIs on motor impairment via mapping of degree centrality (DC) and eigenvector centrality (EC). Results: CMIs carriers had worse motor function than non-carriers. Linear regression analyses showed that CMIs independently contributed to motor function. CMIs carriers had decreased EC in the precuneus, while increased DC and EC in the middle temporal gyrus and increased DC in the inferior frontal gyrus compared to controls (p < 0.05, corrected). Correlation analyses showed that EC of precuneus was related to SPPB (r = 0.25) and balance (r = 0.27); however, DC (r = –0.25) and EC (r = –0.25) of middle temporal gyrus was related with SPPB in all participants (p < 0.05, corrected). Conclusion: CMIs represent an independent risk factor for motor dysfunction. The relationship between CMIs and motor function may be attributed to suppression of functional hub region and compensatory activation of motor-related regions.

scholarly journals Aging-related cerebral microvascular changes visualized using ultrasound localization microscopy in the living mouse

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Matthew R. Lowerison ◽  
Nathiya Vaithiyalingam Chandra Sekaran ◽  
Wei Zhang ◽  
Zhijie Dong ◽  
Xi Chen ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Super Resolution ◽  
Brain Regions ◽  
Blood Velocity ◽  
Aging Brain ◽  
Health Crisis ◽  
Localization Microscopy ◽  
Ultrasound Localization ◽  
Microvascular Changes

AbstractAging-related cognitive decline is an emerging health crisis; however, no established unifying mechanism has been identified for the cognitive impairments seen in an aging population. A vascular hypothesis of cognitive decline has been proposed but is difficult to test given the requirement of high-fidelity microvascular imaging resolution with a broad and deep brain imaging field of view, which is restricted by the fundamental trade-off of imaging penetration depth and resolution. Super-resolution ultrasound localization microscopy (ULM) offers a potential solution by exploiting circulating microbubbles to achieve a vascular resolution approaching the capillary scale without sacrificing imaging depth. In this report, we apply ULM imaging to a mouse model of aging and quantify differences in cerebral vascularity, blood velocity, and vessel tortuosity across several brain regions. We found significant decreases in blood velocity, and significant increases in vascular tortuosity, across all brain regions in the aged cohort, and significant decreases in blood volume in the cerebral cortex. These data provide the first-ever ULM measurements of subcortical microvascular dynamics in vivo within the context of the aging brain and reveal that aging has a major impact on these measurements.

scholarly journals Lexical selection with competing distractors: Evidence from left temporal lobe lesions

2016 ◽  
Author(s):  
Vitória Piai ◽  
Robert T. Knight
Keyword(s):  
Interference Effect ◽  
Temporal Cortex ◽  
Brain Regions ◽  
Error Rates ◽  
Middle Temporal Gyrus ◽  
Lexical Selection ◽  
Semantic Interference ◽  
Middle Temporal ◽  
Relative Contribution ◽  
Unrelated Condition

AbstractAccording to the competition account of lexical selection in word production, conceptually driven word retrieval involves the activation of a set of candidate words in left temporal cortex, and competitive selection of the intended word from this set, regulated by frontal cortical mechanisms. However, the relative contribution of these brain regions to competitive lexical selection is uncertain. In the present study, five patients with left prefrontal cortex lesions (overlapping in ventral and dorsal lateral cortex), eight patients with left lateral temporal cortex lesions (overlapping in middle temporal gyrus), and 13 matched controls performed a picture-word interference task. Distractor words were semantically related or unrelated to the picture, or the name of the picture (congruent condition). Semantic interference (related vs unrelated), tapping into competitive lexical selection, was examined. An overall semantic interference effect was observed for the control and left-temporal groups separately. The left-frontal patients did not show a reliable semantic interference effect as a group. The left-temporal patients had increased semantic interference in the error rates relative to controls. Error distribution analyses indicated that these patients had more hesitant responses for the related than for the unrelated condition. We propose that left middle temporal lesions affect the lexical activation component, making lexical selection more susceptible to errors.

Tactile Angle Discrimination Decreases due to Subjective Cognitive Decline in Alzheimer’s Disease

2020 ◽  
Vol 17 (2) ◽  
pp. 168-176
Author(s):  
Zhilin Zhang ◽  
Guanqun Chen ◽  
Jian Zhang ◽  
Tianyi Yan ◽  
Ritsu Go ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Characteristic Curve ◽  
Subjective Cognitive Decline ◽  
Elderly Subjects ◽  
Older Individuals ◽  
Angle Discrimination

Background: Subjective Cognitive Decline (SCD) is the early preclinical stage of Alzheimer's Disease (AD). Previous study provided an invaluable contribution by showing that a tactile angle discrimination system can be used to distinguish between healthy older individuals and patients with mild cognitive impairment and AD. However, that study paid little attention to the relationship between tactile angle discrimination and SCD. Therefore, a means of differentiating Normal Controls (NCs), elderly subjects with SCD, patients with amnestic Mild Cognitive Impairment (aMCI), and AD is urgently needed. Methods: In the present study, we developed a novel tactile discrimination device that uses angle stimulation applied to the index finger pad to identify very small differences in angle discrimination between the NC (n = 30), SCD (n = 30), aMCI (n = 30), and AD (n = 30) groups. Using a three-alternative forced-choice and staircase method, we analyzed the average accuracy and threshold of angle discrimination. Results: We found that accuracy significantly decreased while thresholds of angle discrimination increased in the groups in the following order: NC, SCD, aMCI, and AD. The area under the receiver operating characteristic curve also indicated that the tactile angle discrimination threshold was better than Mini-Mental State Examination scores in distinguishing NC individuals and SCD patients. Conclusion: These findings emphasize the importance of tactile working memory dysfunction in explaining the cognitive decline in angle discrimination that occurs in SCD to AD patients and offer further insight into the very early detection of subjects with AD.

scholarly journals Indirect White Matter Pathways Are Associated With Treated Naming Improvement in Aphasia

2021 ◽  
pp. 154596832199905
Author(s):  
Janina Wilmskoetter ◽  
Julius Fridriksson ◽  
Alexandra Basilakos ◽  
Lorelei Phillip Johnson ◽  
Barbara Marebwa ◽  
...  
Keyword(s):  
White Matter ◽  
Treatment Outcomes ◽  
Inferior Frontal Gyrus ◽  
Brain Regions ◽  
Angular Gyrus ◽  
Middle Temporal Gyrus ◽  
Middle Temporal ◽  
Pars Opercularis ◽  
Left Hemisphere Stroke ◽  
Linear Regressions

Background White matter disconnection of language-specific brain regions associates with worse aphasia recovery. Despite a loss of direct connections, many stroke survivors may maintain indirect connections between brain regions. Objective To determine (1) whether preserved direct connections between language-specific brain regions relate to better poststroke naming treatment outcomes compared to no direct connections and (2) whether for individuals with a loss of direct connections, preserved indirect connections are associated with better treatment outcomes compared to individuals with no connections. Methods We computed structural whole-brain connectomes from 69 individuals with chronic left-hemisphere stroke and aphasia who completed a 3-week-long language treatment that was supplemented by either anodal transcranial direct current stimulation (A-tDCS) or sham stimulation (S-tDCS). We determined differences in naming improvement between individuals with direct, indirect, and no connections using 1-way analyses of covariance and multivariable linear regressions. Results Independently of tDCS modality, direct or indirect connections between the inferior frontal gyrus pars opercularis and angular gyrus were both associated with a greater increase in correct naming compared to no connections ( P = .027 and P = .039, respectively). Participants with direct connections between the inferior frontal gyrus pars opercularis and middle temporal gyrus who received S-tDCS and participants with indirect connections who received A-tDCS significantly improved in naming accuracy. Conclusions Poststroke preservation of indirect white matter connections is associated with better treated naming improvement in aphasia even when direct connections are damaged. This mechanistic information can be used to stratify and predict treated naming recovery in individuals with aphasia.

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