Xinfeng Yu

Abnormal amygdala function in Parkinson's disease patients and its relationship to depression.

Depression is a common occurrence in patients with Parkinsons disease (PD). Thus, there may be a common neural mechanism underlying the two diseases. Lewy body accumulation in specific brain areas of PD patients may damage emotion-related functions, leading to depression. Among these areas, the amygdala may present with the earliest to be damaged in PD. However, it is still unclear whether amygdala structural and functional changes are related to depression in PD. We enrolled 19 depressed PD patients, 19 non-depressed PD patients, and 28 normal control subjects. Clinical assessment, including the Unified Parkinsons Disease Rating Scale, the Hamilton Rating Scale for Depression, and the Mini-Mental State Examination, was carried out on all the patients. Structural and resting-state functional brain images were also acquired to assess volumetric and functional changes of the amygdala in the patients. Results showed that although there is no significant volume change, left amygdala activity increased in the PD group compared with the normal control group, and it correlated with Hamilton Rating Scale for Depression scores. Furthermore, functional connectivity between the right amygdala and fronto-parietal areas was found to be decreased in the depressed PD patients compared with non-depressed PD patients. These results suggest that abnormal amygdala function may underlie the occurrence of depression in PD.

Disrupted white matter integrity in depressed versus non-depressed Parkinson's disease patients: A tract-based spatial statistics study

Depression is a common occurrence in patients with Parkinsons disease (PD), however, its pathophysiology still remains unclear. With increasing evidence suggesting that depression is a disconnection syndrome, we hypothesized that depression in PD is caused by degenerated fiber connections in the brain. We examined whole brain white matter integrity in 15 depressed PD patients and 15 non-depressed PD patients. All the patients were assessed with the Unified Parkinsons Disease Rating Scale, the Hamilton Rating Scale for Depression, and the Mini-Mental State Examination. White matter difference between the two groups and its correlation with disease severity was calculated. In depressed PD patients, decreased fractional anisotropy was found in the left uncinate fasciculus, superior longitudinal fasciculus, anterior thalamic radiation, forceps minor, and the inferior longitudinal fasciculus. Fractional anisotropy in the left deep temporal cortex was negatively correlated with severity of depression (r = -0.671, p = 0.034). Our results suggest that disrupted fiber connections in the anterior part of the left hemisphere may contribute to depression in PD patients.

Blood Brain Barrier Disruption in Diabetic Stroke Related to Unfavorable Outcome

Background: Diabetes mellitus (DM) is associated with a wide range of microvascular abnormalities in the brain. These include the dysfunction of the blood brain barrier (BBB). In this study, we test the hypotheses that disruption of the BBB in patients presenting with acute stroke is common in patients with DM and is related to outcome. Methods: Sixty-two consecutive patients with ischemic stroke in the middle cerebral artery territory were enrolled within 3-7 days after onset. In ischemic lesion, BBB disruption was detected by parenchymal enhancement (PE) on 5 min delayed post-contrast T1 weighted imaging. National Institute of Health Stroke Score (NIHSS) assessed neurologic impairment on admission. Clinical outcome at 3 months was classified as unfavorable if the modified Rankin scale was >1. The independent factors associated with clinical outcome were analyzed using multivariate logistic regression analysis and OR with its 95% CIs were estimated. Results: An unfavorable stroke outcome was found in 19 diabetic patients and 21 non-diabetic patients. Diabetic patients had a significantly higher frequency of PE than non-diabetic patients (58.6 vs. 27.3%, p = 0.013) and DM was independently associated with PE (OR 4.40; 95% CI 1.22-15.83; p = 0.023). PE was significantly more common in diabetic patients with unfavorable stroke outcome (73.7%) than in other 3 subgroups: diabetic patients with favorable stroke outcome (30.0%), non-diabetic patients with favorable stroke outcome (38.1%) and unfavorable stroke outcome (8.3%; p = 0.002). PE was independently associated with unfavorable outcome (UO) in diabetic stroke (DS; OR 7.04; 95% CI 1.20-41.52; p = 0.031). Admission NIHSS score was associated with UO in non-DS (NDS) (OR 1.71; 95% CI 1.10-2.66; p = 0.017). Conclusions: Compared with NDS, DS had increased BBB disruption defined by the presence of PE. A different form of the relationship between admission NIHSS and UO in NDS, BBB disruption was related with UO in diabetic patients after stroke.

Associations between APOE genotype and cerebral small-vessel disease: a longitudinal study

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

Decreased Inter-Hemispheric Functional Connectivity in Cognitively Intact Elderly APOE ɛ4 Carriers: A Preliminary Study

The apolipoprotein E (APOE) ɛ4 allele is the best-known genetic risk factor for developing sporadic Alzheimers disease (AD). According to neuroimaging studies, the APOE ɛ4 allele is associated with localized altered brain function. However, in long-range circuitry, APOE ɛ4 allele-related alterations in functional communication between hemispheres have rarely been directly investigated. We examined the alteration of resting-state functional connectivity (RSFC) between inter-hemispheric homotopic regions in cognitively intact, elderly APOE ɛ4 carriers. The voxel-mirrored homotopic connectivity method was used to assess the inter-hemispheric RSFC. The current study included 13 cognitively intact, elderly APOE ɛ4 carriers (with at least one copy of APOE ɛ4 allele) and 22 well-matched ɛ3 homozygotes. Comparisons between the two groups were conducted, and subsequently, the correlation between the differential inter-hemispheric RSFC and cognitive ability was analyzed. Compared with ɛ3 homozygotes, APOE ɛ4 carriers showed decreased inter-hemispheric RSFC in the bilateral medial temporal lobe (MTL) and orbital frontal cortex (OFC). Moreover, in APOE ɛ4 carriers, the inter-hemispheric RSFC of the MTL correlated with the Wechsler Memory Scale-Logical Memory (WMS-LM) (immediate and delayed performance, r = 0.64, p <  0.05; r = 0.65, p <  0.05, respectively), and the inter-hemispheric RSFC of the OFC correlated with the WMS-LM delayed performance (r = 0.71, p <  0.05). In our study, the presence of the APOE ɛ4 allele was linked with decreased inter-hemispheric RSFC, which was attributed to memory performance in carriers.

Altered spontaneous activity of posterior cingulate cortex and superior temporal gyrus are associated with a smoking cessation treatment outcome using varenicline revealed by regional homogeneity

Compared to nonsmokers, smokers exhibit a number of potentially important differences in regional brain function. However, little is known about the associations between the local spontaneous brain activity and smoking cessation treatment outcomes. In the present analysis, we aimed to evaluate whether the local features of spontaneous brain activity prior to the target quit date was associated with the smoking cessation outcomes. All the participants underwent magnetic resonance imaging scans and smoking-related behavioral assessments. After a 12-week treatment with varenicline, 23 smokers succeeded in quitting smoking and 32 failed. Smokers underwent functional magnetic resonance imaging (fMRI) scanning prior to an open label smoking cessation treatment trial. Regional homogeneity (ReHo) was used to measure spontaneous brain activity, and whole-brain voxel-wise comparisons of ReHo were performed to detect brain regions with altered spontaneous brain activity between relapser and quitter groups. After controlling for potentially confounding factors including years of education, years smoked, cigarettes smoked per day and FTND score as covariates, compared to quitters, relapsers displayed significantly decreased ReHo in bilateral posterior cingulate cortex (PCC), as well as increased ReHo in left superior temporal gyrus (STG). These preliminary results suggest that regional brain function variables may be promising predictors of smoking relapse. This study provided novel insights into the neurobiological mechanisms underlying smoking relapse. A deeper understanding of the neurobiological mechanisms associated with relapse may result in novel pharmacological and behavioral interventions.

Affect of APOE on information processing speed in non-demented elderly population: a preliminary structural MRI study

APOE is one of the strongest genetic factors associated with information processing speed (IPS). Herein, we explored the neural substrates underlying APOE-related IPS alteration by measuring lobar distribution of white matter hyperintensities (WMH), cortical grey matter volume (GMV) and thickness. Using the ADNI database, we evaluated 178 cognitively normal elderly individuals including 34 APOE ε2 carriers, 54 APOE ε4 carriers and 90 ε3 homozygotes. IPS was determined using Trail Making Tests (TMT). We quantified lobar distribution of WMH, cortical GM lobar volume, cortical thickness among three groups. Finally, we used Pearson’s correlation and general linear models to examine structural MRI markers in relation to IPS. There were significant differences of IPS among groups, with ε4 carriers displaying the worst performance. Across groups, significant differences in frontal and parietal WMH load were observed (the highest in ε4 carriers); however, no significant differences in cortical GMV and thickness were found. Pearson’s correlation analysis showed parietal WMH volume was significantly related with IPS, especially in ε4 carriers. Subsequently a general linear model demonstrated that parietal WMH volume, age and the interaction between parietal WMH volume and age, was significantly associated with IPS, even after adjusting total intracranial volume (TIV), gender and vascular risk factors. Disruption of WM structure, rather than atrophy of GM, plays a more critical role in APOE ε4 allele-specific IPS. Moreover, specific WMH loci are closely associated with IPS; increased parietal WMH volume, especially in ε4 carriers, was independently contributed to slower IPS.

Better Correlation of Cognitive Function to White Matter Integrity than to Blood Supply in Subjects with Leukoaraiosis

Leukoaraiosis is associated with increased risk of cognitive impairment, but its pathophysiological pathway is unclear. The aim of the present study was to determine whether brain structural damage or cerebral blood supply better correlated with the global cognitive outcome in subjects with leukoaraiosis. Seventy-five subjects with leukoaraiosis were included in present study, with age ranged from 43 to 85 years, with mean white matter hyperintensities (WMH) volume 30.69 ± 24.35 mL. Among them, 19(25.33%) subjects presented with cerebral microbleeds (CMB) and 40 (53.33%) subjects presented with lacunes. These participants received arterial spin labeling perfusion MRI, diffusion-tensor imaging (DTI) and diffusion Kurtosis imaging. We analyzed the cerebral blood flow (CBF) by dividing the brain tissue into three regions: WMH, normal appearing white matter (NAWM) and cortex. After adjusting for age and gender, the CBF of NAWM was significantly correlated with fractional anisotropy (FA) (r = 0.336, p = 0.004) and mean diffusion (MD) (r = -0.271, p = 0.020) of NAWM, while there lacked of association between CBF of cortex and mean kurtosis (MK) of cortex (r = -0.015, p = 0.912). Meanwhile, both NAWM-FA (r = -0.443, p < 0.001) and NAWM-MD (r = 0.293, p = 0.012), as well as cortex-MK (r = -0.341, p = 0.012) was significantly correlated with WMH volume. Univariate regression analysis demonstrated that global cognitive function was significantly associated with mean FA or MD of both WMH and NAWM, and cortex-CBF, but neither with the cortex-MK, nor the presences of CMB or lacunes. Finally, multiple linear regression analysis revealed that global cognitive function was independently associated with NAWM-FA (standardized β = 0.403, p < 0.001) and WMH-FA (Standardized β = 0.211, p = 0.017), but not with the cortex-CBF. A model that contained NAWM-FA, WMH-FA and years of education explained 49% of the variance of global cognitive function. Cerebral perfusion status might have a significant impact on the maintenance of white matter integrity in subjects with leukoaraiosis. Global cognitive function was more strongly associated with white matter integrity than with blood supply. DTI parameters, especially FA could serve as a potent imaging indicator for detecting the invisible alteration of white matter integrity and implying its potential cognitive relevance.

White matter injury induced by diabetes in acute stroke is clinically relevant: A preliminary study

The importance of white matter injury induced by diabetes in stroke severity and prognosis is largely unknown. We aimed to investigate the relationship between diabetes-related white matter injury beyond stroke lesions with acute neurological deficits and clinical outcome after stroke. In total, 36 stroke patients within 3–7 days after onset were enrolled. Neurological deficits on admission were assessed by National Institute of Health Stroke Score, and poor outcome at 3 months was defined as modified Rankin score >2. White matter tracts were compared between patients with diabetic and non-diabetic stroke using fractional anisotropy from diffusion tensor imaging. Regional white matter abnormality with decreased fractional anisotropy was observed in diabetic patients (n = 18) when compared to non-diabetic patients (n = 18). Decreased fractional anisotropy in ipsilesional distal corticospinal tract was independently associated with higher National Institute of Health Stroke Score motor component score (β = −0.444, p = 0.005), and decreased fractional anisotropy in contralesional superior longitudinal fasciculus I was independently related to poor outcome (odds ratio, 0.900; p = 0.033). Our findings suggested that only white matter injury induced by diabetes in specific tracts like corticospinal tract and superior longitudinal fasciculus beyond stroke lesions has clinically relevant, providing insight into the mechanism of stroke recovery under the diabetic condition.

Quantitative susceptibility mapping as a biomarker for evaluating white matter alterations in Parkinson’s disease

Myelinated white matter showing diamagnetic susceptibility is important for information transfer in the brain. In Parkinson’s disease (PD), the white matter is also suffering degenerative alterations. Quantitative susceptibility mapping (QSM) is a novel technique for noninvasive assessment of regional white matter ultrastructure, and provides different information of white matter in addition to standard diffusion tensor imaging (DTI). In this study, we used QSM to detect spatial white matter alterations in PD patients (n = 65) and age- and sex-matched normal controls (n = 46). Voxel-wise tract-based spatial statistics were performed to analyze QSM and DTI data. QSM showed extensive white matter involvement—including regions adjacent to the frontal, parietal, and temporal lobes—in PD patients, which was more widespread than that observed using DTI. Both QSM and DTI showed similar alterations in the left inferior longitudinal fasciculus and right cerebellar hemisphere. Further, alterations in the white matter were correlated with motor impairment and global disease severity in PD patients. We suggest that QSM may provide a novel approach for detecting white matter alterations and underlying network disruptions in PD. Further, the combination of QSM and DTI would provide a more complete evaluation of the diseased brain by analyzing different biological tissue properties.