The use of individual-based FDG-PET volume of interest in predicting conversion from mild cognitive impairment to dementia.

BACKGROUND: Based on a longitudinal cohort design, the aim of this study was to investigate whether individual-based 18F fluorodeoxyglucose positron emission tomography (18F-FDG-PET) regional signals can predict dementia conversion in patients with mild cognitive impairment (MCI). METHODS: We included 44 MCI converters (MCI-C), 38 non-converters (MCI-NC), 42 patients with Alzheimer's disease with dementia, and 40 cognitively normal controls. Data from annual cognitive measurements, 3D T1 magnetic resonance imaging (MRI) scans, and 18F-FDG-PET scans were used for outcome analysis. An individual-based FDG-PET approach was applied using seven volumes of interest (VOIs), Z transformed using a normal FDG-PET template. Hypometabolism was defined as a Z score < -2 of regional standard uptake value ratio. For the longitudinal cognitive test scores, generalized estimating equations were used. A linear mixed-effects model was used to compare the temporal impact of cortical hypometabolism and cortical thickness degeneration. RESULTS: The clinical follow-up period was 6.6 ± 3.8 years (range 3.1 to 16.0 years). The trend of cognitive decline could differentiate MCI-C from MCI-NC after 3 years of follow-up. In the baseline 18F-FDG-PET scan of the patients with MCI, medial temporal lobe (MTL; 94.7% sensitivity, 80.5% specificity) and posterior cingulate cortex (PCC; 89.5% sensitivity, 73.1% specificity) hypometabolism predicted conversion with high accuracy. 18F-FDG-PET hypometabolism preceded dementia conversion at an interval of 3.70 ± 1.68 years and was earlier than volumetric changes, with the exception of the MTL. CONCLUSIONS: Our finding supports the use of individual-based 18F-FDG-PET analysis to predict MCI conversion to dementia. Reduced FDG-PET metabolism in the MTL and PCC were strongly associated with future cognitive decline in the MCI-C group. Changes in 18F-FDG-PET occurred 1 to 8 years prior to conversion to dementia. Progressive hypometabolism in the PCC, precuneus and lateral temporal lobe, but not MTL, preceded MRI findings at the MCI stage.

Association of Cognition and Brain Reserve in Aging and Glymphatic Function Using Diffusion Tensor Image-along the Perivascular Space (DTI-ALPS).

The glymphatic system is a fluid-clearance pathway that clears cerebral waste products, and its dysfunction has been associated with protein aggregation diseases such as Alzheimer's disease. To understand how the glymphatic system changes with aging, we enrolled 433 cognitive unimpaired participants (236 women and 197 men, 13-88 years) and evaluated the glymphatic function by calculating diffusion tensor imaging analysis along the perivascular space (ALPS) index and explored how the ALPS index is associated with cortical atrophy and cognitive decline in older people. We found a significant inverse correlation between ALPS index and age (ρ = -0.45, p < 0.001), with a peak value in people in their thirties. A higher ALPS index indicated a better cortical reserve in regions coincided with the default mode network. Declines in mental manipulation and short-term memory performance in the older participants were associated with a lower ALPS index and cortical atrophy in the amygdala, anterior and posterior cingulate, thalamus and middle frontal regions. Our findings highlight that the ALPS index could be used to evaluate brain reserve and cognitive reserve in older people.

Clinical significance of fractional anisotropy in cerebral white matter regional vulnerability caused by carbon monoxide poisoning: A systematic review and meta-analysis.

Carbon monoxide poisoning (COP) can lead to various cerebral white matter (WM) lesions across different disease phases and clinical manifestations, and fractional anisotropy (FA) of diffusion tensor imaging has been widely applied to investigate WM injury in these patients. Here we conducted a systematic review and meta-analysis to investigate the utility of FA in evaluating the regional vulnerability of WM injury caused by COP and explore differences between different disease phases and patient subtypes. We systematically searched PubMed, Medline, Scopus and reference lists of appropriate publications to identify relevant studies. Eight studies with 217 patients with COP and 207 healthy controls (HCs) were included. Eight regions of interest were available to investigate regional vulnerability. The results showed the most significant decrease in FA in orbitofrontal subcortical regions. Comparisons of different disease phases revealed lower FA in the centrum semiovale and corpus callosum in the acute phase, while in the chronic phase, only FA in the centrum semiovale remained significantly decreased. Analysis of different patient subtypes showed that the FA values in the splenium of the corpus callosum were significantly decreased in the patients with delayed neurologic sequelae (DNS) but not in the mixed population (with and without DNS). In conclusion, this meta-analysis highlights the frontal-subcortical regional vulnerability in COP. FA changes in the corpus callosum across different disease phases reflect alterations in underlying microstructures. Extended corpus callosum injury involving the splenium could be an imaging biomarker of the occurrence of DNS.

Neuropsychiatric Symptoms and Caregiver Stress in Parkinson's Disease with Cognitive Impairment, Alzheimer's Disease, and Frontotemporal Dementia.

BACKGROUND: A better understanding of factors associated with caregiver burden might facilitate the construction of coping strategies to improve their clinical outcomes and the comprehensive care model for dementia. OBJECTIVE: To investigate the cognitive and neuropsychiatric domains that contribute to caregiver burden in three types of neurodegenerative disorders: Parkinson's disease (PD), Alzheimer's disease (AD), and frontotemporal disease (FTD). METHODS: Eight hundred and fourteen patients and their caregivers were invited to participate; among them, 235 had PD with cognitive impairment; 429 had AD, and 150 had FTD. The evaluation protocol included the Neuropsychiatric Inventory (NPI), the Mini-Mental State Examination, the Chinese Version Verbal Learning Test, the modified Trail Making Test B, semantic fluency, and a geriatric depression score. Statistical comparisons of the cognitive tests, NPI total scores, and caregiver burden among the three diagnosed types of dementia, matched for a Clinical Dementia Rating (CDR) of 0.5 or 1, were performed, and multivariate linear regression models were used to evaluate the parameter significance. RESULTS: Caregivers for patients with PD and FTD showed significant burden increments when the CDR scores changes from 0.5 to 1. For CDR = 0.5, the PD group had significantly lower caregiver burdens than the AD group, but the NPI total scores were significantly higher. Factors related to caregiver burden were the presence of delusion among all diagnosis groups, while the impact of NPI total scores related to caregiver burden was the highest in FTD, followed by AD and PD. CONCLUSIONS: At the mild to moderate stages, our results suggested different degrees of significance in terms of the cognitive test scores or NPI subdomains for predicting caregiver stress among the three types of dementia.

Impact of Amyloid Pathology in Mild Cognitive Impairment Subjects: The Longitudinal Cognition and Surface Morphometry Data.

The amyloid framework forms the central medical theory related to Alzheimer disease (AD), and the in vivo demonstration of amyloid positivity is essential for diagnosing AD. On the basis of a longitudinal cohort design, the study investigated clinical progressive patterns by obtaining cognitive and structural measurements from a group of patients with amnestic mild cognitive impairment (MCI); the measurements were classified by the positivity (Aß+) or absence (Aß-) of the amyloid biomarker. We enrolled 185 patients (64 controls, 121 patients with MCI). The patients with MCI were classified into two groups on the basis of their [18F]flubetaben or [18F]florbetapir amyloid positron-emission tomography scan (Aß+ vs. Aß-, 67 vs. 54 patients) results. Data from annual cognitive measurements and three-dimensional T1 magnetic resonance imaging scans were used for between-group comparisons. To obtain longitudinal cognitive test scores, generalized estimating equations were applied. A linear mixed effects model was used to compare the time effect of cortical thickness degeneration. The cognitive decline trajectory of the Aß+ group was obvious, whereas the Aß- and control groups did not exhibit a noticeable decline over time. The group effects of cortical thickness indicated decreased entorhinal cortex in the Aß+ group and supramarginal gyrus in the Aß- group. The topology of neurodegeneration in the Aß- group was emphasized in posterior cortical regions. A comparison of the changes in the Aß+ and Aß- groups over time revealed a higher rate of cortical thickness decline in the Aß+ group than in the Aß- group in the default mode network. The Aß+ and Aß- groups experienced different APOE ε4 effects. For cortical-cognitive correlations, the regions associated with cognitive decline in the Aß+ group were mainly localized in the perisylvian and anterior cingulate regions. By contrast, the degenerative topography of Aß- MCI was scattered. The memory learning curves, cognitive decline patterns, and cortical degeneration topographies of the two MCI groups were revealed to be different, suggesting a difference in pathophysiology. Longitudinal analysis may help to differentiate between these two MCI groups if biomarker access is unavailable in clinical settings.

Cognitive Decline Related to Diet Pattern and Nutritional Adequacy in Alzheimer's Disease Using Surface-Based Morphometry.

Dietary pattern (DP) results in nutrition adequacy and may influence cognitive decline and cortical atrophy in Alzheimer's disease (AD). The study explored DP in 248 patients with AD. Two neurobehavioral assessments (intervals 13.4 months) and two cortical thickness measurements derived from magnetic resonance images (intervals 26.5 months) were collected as outcome measures. Reduced rank regression was used to assess the groups of DPs and a linear mixed-effect model to explore the cortical neurodegenerative patterns. At screening, underweight body mass index (BMI) was related to significant higher lipid profile, impaired cognitive function, smaller cortical thickness, lower protein DP factor loading scores and the non-spouse caregiver status. Higher mini-mental state examination (MMSE) scores were related to the DP of coffee/tea, compared to the lipid/sugar or protein DP group. The underweighted-BMI group had faster cortical thickness atrophy in the pregenual and lateral temporal cortex, while the correlations between cortical thickness degeneration and high HbA1C or low B12 and folate levels were localized in the medial and lateral prefrontal cortex. The predictive model suggested that factors related to MMSE score were related to the caregiver status. In conclusion, normal or overweight BMI, coffee/tea DP group and living with a spouse were considered as protective factors for better cognitive outcomes in patients with AD. The influence of glucose, B12 and folate on the cortical degeneration was spatially distinct from the pattern of AD degeneration.

Functional MRI and ApoE4 genotype for predicting cognitive decline in amyloid-positive individuals.

Background: In light of advancements in machine learning techniques, many studies have implemented machine learning approaches combined with data measures to predict and classify Alzheimer's disease. Studies that predicted cognitive status with longitudinal follow-up of amyloid-positive individuals remain scarce, however. Objective: We developed models based on voxel-wise functional connectivity (FC) density mapping and the presence of the ApoE4 genotype to predict whether amyloid-positive individuals would experience cognitive decline after 1 year. Methods: We divided 122 participants into cognitive decline and stable cognition groups based on the participants' change rates in Mini-Mental State Examination scores. In addition, we included 68 participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) database as an external validation data set. Subsequently, we developed two classification models: the first model included 99 voxels, and the second model included 99 voxels and the ApoE4 genotype as features to train the models by Wide Neural Network algorithm with fivefold cross-validation and to predict the classes in the hold-out test and ADNI data sets. Results: The results revealed that both models demonstrated high accuracy in classifying the two groups in the hold-out test data set. The model for FC demonstrated good performance, with a mean F 1-score of 0.86. The model for FC combined with the ApoE4 genotype achieved superior performance, with a mean F 1-score of 0.90. In the ADNI data set, the two models demonstrated stable performances, with mean F 1-scores of 0.77 in the first and second models. Conclusion: Our findings suggest that the proposed models exhibited promising accuracy for predicting cognitive status after 1 year in amyloid-positive individuals. Notably, the combination of FC and the ApoE4 genotype increased prediction accuracy. These findings can assist clinicians in predicting changes in cognitive status in individuals with a high risk of Alzheimer's disease and can assist future studies in developing precise treatment and prevention strategies.

Functional Connectivity, Physical Activity, and Neurocognitive Performances in Patients with Vascular Cognitive Impairment, No Dementia.

BACKGROUND: Vascular Cognitive Impairment, No Dementia (VCIND) is a key stage at which early intervention will delay or prevent dementia. The pathophysiology of VCIND posits that a lesion in a single location in the brain has the ability to disrupt brain networks, and the subsequent abnormal Functional Connectivity (FC) of brain networks leads to deficits in corresponding neurobehavioral domains. In this study, we tested the hypothesis that disrupted anterior cingulate cortex and striatal networks mediated the effects of Physical Activity (PA) on neurobehavioral function. METHODS: In 27 patients with VCIND, FC within the brain networks and neurobehavioral dysfunction were assessed. The relationship between the cognitive scores, FC, and PA was studied. The Fitbit Charge 2 was used to measure step counts, distance, and calories burned. In patients with VCIND, a cross-sectional Spearman's correlation to analyze the relationship among patient-level measures of PA, cognitive function scores, and FC strength within the brain networks. RESULTS: Average step counts and average distance were associated with Trail Making Test B (TMB) time to completion (seconds) and Instrumental Activities of Daily Living (IADL) score (P < 0.05). The average calories burned were associated with IADL score (P = 0.009). The FC within the brain networks anchored by left caudal Anterior Cingulate Cortex (ACC) seeds (x= -5, y= 0, z= 36) and (x= -5, y= -10, z= 47) were positively correlated with average step counts and average distance, were negatively correlated with TMB time to completion (seconds), and were positively correlated with IADL score (P < 0.05). The FC within the brain networks anchored by left subgenual ACC seed (x= -5, y= 25, z= -10) were negatively correlated with average step counts and average distance were positively correlated with TMB time to completion (seconds), and were negatively correlated with IADL score (P < 0.05). The FC within the striatal networks was positively correlated with average calories burned and IADL score (P < 0.05). CONCLUSION: FC within the brain networks anchored by caudal ACC seeds was positively correlated with more average step counts/average distance and better IADL score; negatively correlated with longer TMB time to completion (seconds), whereas FC of subgenual ACC seed was negatively correlated with the same parameters. FC within the brain networks anchored by putamen rather than caudate or pallidum was positively correlated with average calories burned and IADL score.

Structural Covariance Network as an Endophenotype in Alzheimer's Disease-Susceptible Single-Nucleotide Polymorphisms and the Correlations With Cognitive Outcomes.

The cognitive manifestations of Alzheimer's disease (AD) are related to brain network degeneration, and genetic differences may mediate network degeneration. Several AD-susceptible loci have been reported to involve amyloid or tau cascades; however, their relationships with gray matter (GM) volume and cognitive outcomes have yet to be established. We hypothesized that single-nucleotide polymorphism genotype groups may interact with apolipoprotein E4 (ApoE4) status or independently exert an effect on cognitive outcomes. We also hypothesized that GM structural covariance networks (SCNs) may serve as an endophenotype of the genetic effect, which, in turn, may be related to neurobehavior test scores. Gray matter SCNs were constructed in 324 patients with AD using T1 magnetic resonance imaging with independent component analysis (ICA). We assessed the effects of 15 genetic loci (rs9349407, rs3865444, rs670139, rs744373, rs3851179, rs11136000, rs3764650, rs610932, rs6887649, rs7849530, rs4866650, rs3765728, rs34011, rs6656401, and rs597668) using additive, recessive, and dominant models on cognitive outcomes. Statistical analysis was performed to explore the independent role of each locus, interactions with ApoE4 status, and relationships to GM ICA network intensity score. For outcome measures, we used the Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI) total score, and short-term memory (STM) subscores, adjusted for the covariates of education, disease duration, and age. Clinically, the CD2AP G allele showed a protective role in MMSE, CASI total, and CASI-STM scores independently or via interactions with non-ApoE4 status, while the CR1 A genotype group was associated with lower STM subscores independent of ApoE4 status. Three loci showed synergic interactions with ApoE4: BIN 1, MS4A6A, and FTMT. Of the 15 meaningful ICA components, 5 SCNs (anterior and posterior hippocampus, right temporal, left thalamus, default mode network) showed relationships with general cognitive performance, in which only the ApoE4 and MS4A6A genotype groups were independently related to the hippocampus network. The genetic loci MS4A6A, BIN1, CLU, CR1, BIN1, PICALM, and FGF1 influenced the networks independently or in synergy. This study suggests that AD-susceptible loci may each exert clinical significance independently through interactions with ApoE4 status or through SCNs as an endophenotype and that this effect is associated with the cognitive outcomes.

Dynamic contrast-enhanced magnetic resonance imaging in correlation with tongue cancer stages.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) plays a significant role in tumor stage as it can be used to measure tissue perfusion and permeability of tumors. PURPOSE: To investigate the relationships between both quantitative and semi-quantitative variables obtained from DCE-MRI and tongue cancer stages. MATERIAL AND METHODS: Mean values of Ktrans, enhancement ratio (ER), wash-in slope (slope), and the 95th percentile (95%) values of the distribution for Ktrans, ER, and slope values (Ktrans (95%), ER (95%), and slope (95%), respectively) were calculated for 53 patients with tongue cancers (American Joint Committee on Cancer 8th Edition stage group: 10 in stages I and II, 14 in stage III, 21 in stage IVa, and eight in stage IVb as determined by histopathologic assessment). The relationship between tumor staging and each of the six DCE-MRI parameters was assessed separately using ordinal logistic regression. RESULTS: The logistic regression analysis revealed that both mean and 95th percentile values of Ktrans were significantly and positively correlated with tongue cancer stage (P < 0.01). More aggressive tumor stages had larger kinetic parameter. Moreover, the semi-quantitative parameters, such as ER (95%) and slope (95%), may be more significant predictors for evaluating tongue cancer stages than the mean ER and mean slope. CONCLUSION: Both quantitative and semi-quantitative imaging biomarkers are useful for evaluating the stages of tongue cancer, and the indices obtained from DCE-MRI were positively correlated with the tumor stages. These parameters have the potential to non-invasively evaluate the stages of tongue cancer in the clinical setting.

Functional connectivity in default mode network correlates with severity of hypoxemia in obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA)-associated hypoxemia, sleep fragmentation, and cerebral vascular dysfunction are implicated in cognitive dysfunction. Functional connectivity within default mode network (DMN) is a possible mechanism underlying the cognitive impairment. The aim of this study was to investigate the impact of hypoxemia and sleep fragmentation on functional connectivity and on cognitive performance in patients with OSA. METHODS: Twenty-eight patients with OSA were included (mean age = 58.0 ± 8.5 years). We correlated the functional connectivity in DMN with cognitive performances and further analyzed the relationship of functional connectivity in DMN with hypoxemia severity, as revealed by apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and nadir SaO2 (%), and with degree of sleep fragmentation, as shown by sleep efficiency and wake after sleep onset. RESULTS: Functional connectivity in DMN was associated with AHI, ODI, and nadir SaO2 (%) (p < .05) and was not associated with sleep fragmentation measures (p > .05). Functional connectivity that was associated with AHI, ODI, and nadir SaO2 (%) was in the areas of bilateral middle temporal gyri, bilateral frontal pole, and bilateral hippocampus and was positively correlated with Cognitive Abilities Screening Instrument (CASI) total score (ρ = 0.484; p = .012), CASI-List-generating, CASI-Attention, and composite score of CASI-List-generating plus CASI-Attention (p < .05). CONCLUSION: Functional connectivity in DMN is implicated in impairment of global cognitive function and of attention in OSA patients. The functional connectivity in the DMN is associated with hypoxemia rather than with sleep fragmentation.

Functional connectome and neuropsychiatric symptom clusters of Alzheimer's disease.

BACKGROUND: Neuropsychiatric symptoms (NPSs) are important aspects of Alzheimer's disease (AD). Investigation of the effect of functional network abnormalities on clustered NPSs may uncover loci of altered connectivity for more targeted pharmacological and behavioral interventions in AD. The study aimed to investigate functional connectivity in AD and the clustered NPSs, as assessed by the Neuropsychiatric Inventory (NPI). METHODS: In one hundred and fifty-nine patients with mild dementia stage of AD, graph metrics measuring functional connectivity at global network- and local network-level were assessed by closeness-centrality, betweenness-centrality, average-path-length, local-efficiency, and clustering-coefficient, respectively. The relationship between the NPI composite score and functional connectivity was assessed. RESULTS: In AD, an increase in behavioral composite score was associated with changes in functional connectivity at local network-level, and regions displayed the changes was left lingual gyrus, left sub-genual ACC nodes, and left supra-genual ACC nodes (P < 0.05). An increase in affective composite score was associated with changes in functional connectivity at global network-level, and regions displayed the change was right caudate (P = 0.014). An increase in psychotic composite score was associated with changes in functional connectivity at global network-level, and regions displayed the change was left precuneus and right dorsolateral superior frontal gyrus (P < 0.05). LIMITATIONS: Cognitively normal elderly subjects and longitudinal follow-up will be needed to see the evolution of NPS clusters and pathological changes in the functional connectivity at global or local network-level. CONCLUSIONS: Different NPS clusters corresponded to distinct changes in functional connectivity at global and local network-level.

Renal Damages in Deoxycorticosterone Acetate-Salt Hypertensive Rats: Assessment with Diffusion Tensor Imaging and T2-mapping.

PURPOSE: This study aimed to investigate the feasibility of diffusion tensor imaging (DTI) and T2-mapping to assess temporal renal damage in deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats and compare the results with histopathologic and immunohistochemical findings. PROCEDURES: After baseline renal magnetic resonance imaging (MRI), 24 out of 30 uninephrectomized Sprague-Dawley rats with DOCA-salt-induced hypertension were divided equally into four groups. Group 1 had renal MRI at weeks 2, 4, 6, and 8, and groups 2, 3, and 4 had MRI at weeks 2, 4, and 6, respectively. The remaining 6 rats were used as sham controls. The renal cortex and outer and inner stripes of the outer medulla were examined over time using fractional anisotropy (FA), apparent diffusion coefficient (ADC), and T2-mapping, and the results were compared with baseline values. The degree of glomerular and tubular injury, endothelial cell thickening, hyaline arteriolosclerosis, macrophage infiltration, microcyst formation, and fibrosis in different zones at different time points in the DOCA-salt rats were compared with controls. RESULTS: Compared with baseline values, DOCA-salt rats demonstrated a significant decrease in renal cortical FA from week 4 to week 8 (0.244 ± 0.015 vs 0.172 ± 0.014-0.150 ± 0.016, P = 0.018-0.002), corresponding to significantly more glomerular damage, arteriolosclerosis, macrophage infiltration, and fibrosis. The DOCA-salt rats had significantly increased cortical ADC and T2 values at weeks 6 and 8 (1.778 ± 0.051 × 10-3 mm2/s vs 1.872 ± 0.058-1.917 ± 0.066 × 10-3 mm2/s; 93.7 ± 4.9 ms vs 98.0 ± 2.9-100.7 ± 4.0 ms, respectively, all P < 0.05), consistent with excessively fluid-filled microcysts (aquaporin-2+). Despite DOCA-salt rats harbored markedly increased fibrosis in outer and inner stripes of the outer medulla at weeks 6 and 8, only nonsignificant decreases in FA were observed in comparison with the controls suggesting that only limited microstructural changes were present. CONCLUSIONS: Renal cortical FA is useful for the early detection and monitoring of renal damage in DOCA-salt hypertensive rats.

ABCA7 polymorphisms correlate with memory impairment and default mode network in patients with APOEε4-associated Alzheimer's disease.

BACKGROUND: Since both APOE and ABCA7 protein expression may independently reduce neuritic plaque burden and reorganize fibrillar amyloid burden-mediated disruption of functional connectivity in the default mode network, we aimed to investigate the effect of the APOE-ABCA7 interaction on default mode network in Alzheimer's disease. METHODS: Two hundred and eighty-seven individuals with a diagnosis of typical Alzheimer's disease were included in this study. Memory was characterized and compared between APOE-ε4+ carriers and APOE-ε4 non-carriers within ABCA7 rs3764650T allele homozygous carriers and ABCA7 rs3764650G allele carriers, respectively. Two-way analysis of variance was used to identify a significant interaction effect between APOE (APOE-ε4+ carriers versus APOE-ε4 non-carriers) and ABCA7 (ABCA7 rs3764650T allele homozygous versus ABCA7 rs3764650G allele carriers) on memory scores and functional connectivity in each default mode network subsystem. RESULTS: In ABCA7 rs3764650G allele carriers, APOE-ε4+ carriers had lower memory scores (t (159) = - 4.879; P < 0.001) compared to APOE-ε4 non-carriers, but APOE-ε4+ carriers and APOE-ε4 non-carriers did not have differences in memory (P > 0.05) within ABCA7 rs3764650T allele homozygous carriers. There was a significant APOE-ABCA7 interaction effect on the memory (F3, 283 = 4.755, P = 0.030). In the default mode network anchored by the entorhinal seed, the peak neural activity of the cluster that was significantly associated with APOE-ABCA7 interaction effects (P = 0.00002) was correlated with the memory (ρ = 0.129, P = 0.030). CONCLUSIONS: Genetic-biological systems may impact disease presentation and therapy. Clarifying the effect of APOE-ABCA7 interactions on the default mode network and memory is critical to exploring the complex pathogenesis of Alzheimer's disease and refining a potential therapy.

MAOA-VNTR Genotype Effects on Ventral Striatum-Hippocampus Network in Alzheimer's Disease: Analysis Using Structural Covariance Network and Correlation with Neurobehavior Performance.

Functional polymorphisms in the promoter region of the monoamine oxidase A (MAOA) gene are associated with brain MAOA activity and transcriptional efficiency in patients with Alzheimer's disease (AD). This study investigated structural covariance networks mediated by MAOA-variable number tandem repeat (VNTR) genotypes in patients with AD, and assessed whether this effect was associated with sex. A total of 193 patients with AD were classified into four genotype groups based on MAOA transcriptional efficiency (female low [L], low-high + high activity groups [LH + H]; male L, male H groups). Structural covariance networks were constructed focusing on triple-network and striatal networks. Covariance strength was analyzed in the four groups, and the genotype and sex main effects and their interactions were analyzed. Significant peak cluster volumes were correlated with neurobehavioral scores to establish the clinical significance. MAOA genotypes mediated the structural covariance strength on the dorsolateral prefrontal cortex (dLPFC)-caudate axis in both sexes, but a higher covariance strength was shown in the female L group and male H group. The independent effect of male sex was related to higher covariance strength in the frontal medial superior region in the dLPFC, dorsal caudate (DC), and ventral superior striatum (VSs) seeds. In contrast, female sex had higher covariance strength in the frontal opercular areas anchored by the dLPFC, DC, and VSs seeds. Topographies showing higher covariance strength with sex interactions were found in the male H group and female L group in the dLPFC supplementary motor axis, DC-SMA, and DC-precentral axis. In our patients with AD, MAOA-VNTR polymorphisms and sex had independent and interactive effects on structural covariance networks, of which the dLPFC-, VSs-, and DC-anchored networks represented major endophenotypes that determined cognitive outcomes. The sex-genotype interaction model suggested that male high activity and female low activity may modulate brain morphometric connectivity and determine cognitive scores.

Diffusion kurtosis imaging as a neuroimaging biomarker in patients with carbon monoxide intoxication.

Attempting suicide by burning charcoal can lead to carbon monoxide (CO) intoxication and cognitive deficits. Changes in white matter (WM) quantified by diffusion tensor imaging (DTI)-derived parameters have been validated to reflect cognitive test scores. As diffusion kurtosis imaging (DKI) measures biological microstructures using non-Gaussian diffusivity, we assessed the added-information of DKI with neuropsychological test scores as the major outcome measure. A total of 45 patients were enrolled and compared with 30 age-matched controls. The patients were stratified into acute or chronic phase according to the intervals of intoxication and assessments. WM status was assessed using tract-based spatial statistics for DKI and DTI topographies, and the sensitivity/specificity of either model was tested using area under the curve (AUC) analysis. To evaluate their clinical significance, values of DKI- and DTI-derived parameters were extracted from seven regions of interest (ROI) and correlated with neuropsychiatric scores. The kurtosis parameters were lower in the patients than in the controls but none of the parameters provided differentiations between the acute or chronic phase. Kurtosis fractional anisotropy (KFA) had a higher AUC than fractional anisotropy while the other 3 DTI parameters had higher AUC than the corresponding DKI ones. In clinical correlations, KFA value of right posterior WM correlated with visual memory (r = 0.326, p = 0.029), and KFA values of bilateral posterior WM correlated with the digit forward score (right: r = 0.302, p = 0.043; left: r = 0.314, p = 0.036). Although DTI was more sensitive in reflecting disease status, KFA may be more sensitive and specific than fractional anisotropy in cognitive test score predictions.

Apparent Diffusion Coefficient is a Useful Biomarker for Monitoring Adipose-Derived Mesenchymal Stem Cell Therapy of Renal Ischemic-Reperfusion Injury.

PURPOSE: This study aimed to investigate the potential of apparent diffusion coefficient (ADC) for monitoring adipose-derived mesenchymal stem cell (ADMSC) therapy of renal ischemic-reperfusion injury (IRI). PROCEDURES: After baseline magnetic resonance imaging (MRI), 36 Sprague-Dawley rats with bilateral renal IRI were divided equally as groups 1, 2, and 3 (non-treated rats) and groups 4, 5, and 6 (ADMSC-treated rats, with 2 million ADMSCs injected via the tail vein at 6 h after IRI). Groups 1 and 4, 2 and 5, and 3 and 6 were euthanized at days 1, 3, and 7, respectively, after renal MRI. The ratios of ADC at different time points to baseline values in the cortex, outer, and inner stripes of outer medulla (OSOM/ISOM), assessments of monocyte chemoattractant protein-1 (MCP-1), CD68+ cells, tubular cast formation, and degree of fibrosis in three zones over time were compared between the non-treated and ADMSC-treated rats. RESULTS: Among three zones, the differences in cortical ADC and immunohistochemical changes between the non-treated and ADMSC-treated IRI rats over time were less obvious. Compared with the non-treated rats, the ADMSC-treated rats exhibited significantly higher ADC ratios of OSOM and ISOM at days 1 and 3 corresponding to significantly less MCP-1 staining, CD68+ cells, and tubular casts. From day 3 to day 7, coupling with the decrement of MCP-1 and CD68+ cells in IRI kidneys, the effect of cell density on ADC declined. By day 7, the ADMSC-treated rats showed significantly higher ADC ratios of ISOM than the non-treated IRI rats, indicating better recovery, which could be related to significantly fewer tubular casts and marked amelioration of fibrosis. CONCLUSIONS: We suggest ADC is a useful in vivo biomarker for monitoring ADMSC therapy of renal IRI.

Gestational age, not transient hyperthyrotropinemia impacts brain white matter diffusion tensor imaging in premature infants.

Transient hypothyroidism is common in premature infants and increases the risk of adverse neurodevelopmental outcomes. Thyroid hormone (TH) is involved in oligodendrocyte development and myelination, however, whether transient hypothyroidism is associated with oligodendrocyte dysplasia and abnormal myelination is unclear. The aim of the present study was to investigate correlations among TH levels, neurodevelopmental outcomes and white matter (WM) microstructure in premature infants. The authors designed a cohort study recruiting 81 premature infants (age, 23-35 weeks). A total of 17 were born with a gestational age (GA) <30 weeks (early preterm group) and 64 of them were born with a GA ≥30 weeks (late preterm group). For outcome measurement, thyroid stimulating hormone (TSH) levels at 0, 18, and 24 h of admission were measured. Neurodevelopmental outcomes were assessed using Bayley III test. Diffusion tensor imaging was used to explore the characterization of WM microstructure. The data demonstrated that GA, however not TSH level was associated with neurodevelopmental outcomes in the following 2 years. Fractional anisotrophy (FA) increased with TSH0 levels over anterior limb of internal capsule, while axial diffusivity decreased with TSH0 levels over splenium of corpus callosum (CC). The late preterm group had more intact WM integrity over the internal and external capsule (EC) in FA compared with the early preterm group. Infants with motor dysfunction had significantly increased mean diffusivity (MD) values at regions of interest in the genu and splenium of CC. The results of the present study demonstrated that GA, however not transient hypothyroidism influenced neurodevelopmental outcomes in the premature infants. FA increased with age in a regionally-specific manner over regions of the internal capsule and EC. MD may act as a potential predictor for motor function in premature babies.

Associations of Bcl-2 rs956572 genotype groups in the structural covariance network in early-stage Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a complex neurodegenerative disease, and genetic differences may mediate neuronal degeneration. In humans, a single-nucleotide polymorphism in the B-cell chronic lymphocytic leukemia/lymphoma-2 (Bcl-2) gene, rs956572, has been found to significantly modulate Bcl-2 protein expression in the brain. The Bcl-2 AA genotype has been associated with reduced Bcl-2 levels and lower gray matter volume in healthy populations. We hypothesized that different Bcl-2 genotype groups may modulate large-scale brain networks that determine neurobehavioral test scores. METHODS: Gray matter structural covariance networks (SCNs) were constructed in 104 patients with AD using T1-weighted magnetic resonance imaging with seed-based correlation analysis. The patients were stratified into two genotype groups on the basis of Bcl-2 expression (G carriers, n = 76; A homozygotes, n = 28). Four SCNs characteristic of AD were constructed from seeds in the default mode network, salience network, and executive control network, and cognitive test scores served as the major outcome factor. RESULTS: For the G carriers, influences of the SCNs were observed mostly in the default mode network, of which the peak clusters anchored by the posterior cingulate cortex seed determined the cognitive test scores. In contrast, genetic influences in the A homozygotes were found mainly in the executive control network, and both the dorsolateral prefrontal cortex seed and the interconnected peak clusters were correlated with the clinical scores. Despite a small number of cases, the A homozygotes showed greater covariance strength than the G carriers among all four SCNs. CONCLUSIONS: Our results suggest that the Bcl-2 rs956572 polymorphism is associated with different strengths of structural covariance in AD that determine clinical outcomes. The greater covariance strength in the four SCNs shown in the A homozygotes suggests that different Bcl-2 polymorphisms play different modulatory roles.

Cerebral Perfusion Insufficiency and Relationships with Cognitive Deficits in Alzheimer's Disease: A Multiparametric Neuroimaging Study.

Micro- or macro-circulatory insufficiency has a negative impact in patients with Alzheimer's disease (AD). This study used arterial spin-labeled magnetic resonance imaging (ASL-MRI) and ethylcysteinate dimer single-photon emission computed tomography (ECD-SPECT) in 50 patients with AD and 30 age-matched controls to investigate how hypoperfusion patterns were associated with gray matter atrophy and clinical data. All participants completed 3DT1-MRI, ECD-SPECT and ASL-MRI examinations. Medial temporal cortex (MTC) volumes were correlated with regional signals showing significantly lower relative cerebral blood flow (rCBF) in ASL-MRI or perfusion index (PI) in ECD-SPECT. Neurobehavioral scores served as the outcome measures. Regions with lower PI showed spatial similarities with atrophy in the medial, anterior and superior temporal lobes, posterior cingulate cortex and angular gyrus, while regions showing lower rCBF were localized to the distal branches of posterior cerebral artery territories (posterior parietal and inferior temporal lobe) and watershed areas (angular gyrus, precuneus, posterior cingulate gyrus and middle frontal cortex). rCBF values in watershed areas correlated with MTC volumes and language composite scores. Precuneus and angular gyrus hypoperfusion were associated with the corresponding cortical atrophy. Macro- or micro-vasculature perfusion integrities and cortical atrophy determined the overall perfusion imaging topography and contributed differently to the clinical outcomes.