Dong-Won Yang

Association of cognitive dysfunction with neurocirculatory abnormalities in early Parkinson disease

Objective: Cognitive impairment and neurocirculatory abnormalities such as orthostatic hypotension (OH), supine hypertension (SH), and failure to decrease blood pressure at night (nondipping) occur relatively commonly in Parkinson disease (PD); however, whether cognitive dysfunction in early PD is related to neurocirculatory abnormalities has not been established. Cognitive dysfunction in PD is associated with white matter hyperintensities on MRI. We report results of an analysis of neuropsychological and hemodynamic parameters in patients with early PD. Methods: Among 87 patients, 25 had normal cognition, 48 had mild cognitive impairment, and 14 had dementia, based on comprehensive neuropsychological tests. Orthostatic vital signs and ambulatory 24-hour blood pressure monitoring were recorded, and brain magnetic resonance scans were obtained for all patients. Results: Cognitive impairment was associated with OH, SH, and white matter hyperintensities but not with nondipping. Dementia and white matter hyperintensities were common in SH. Of 13 patients with OH + SH, every one had mild cognitive impairment or dementia. Conclusions: Cognitive dysfunction is related to neurocirculatory abnormalities, especially OH + SH, in early PD, raising the possibility that early detection and effective treatment of those abnormalities might slow the rate of cognitive decline.

Influence of white matter hyperintensities on the cognition of patients with Parkinson disease.

BackgroundWhite matter hyperintensities (WMH) have been associated with cognitive impairment in elderly persons and in patients with Alzheimer disease. However, the role of WMH in Parkinson disease (PD) dementia remains to be elucidated. MethodsThe cohort for this study comprised 71 consecutive patients with PD, all of whom completed a clinical assessment, neuropsychologic investigation, and magnetic resonance imaging of brain. WMH were rated using the semiquantitative visual rating system proposed by Scheltens et al. ResultsThe PD dementia group had significantly more WMH than the PD without dementia group in the evaluated brain regions except for the infratentorial area. The WMH showed a significant correlation with age, Unified Parkinsons Disease Rating Scale, Mini-Mental State Examination, sum of the box of Clinical Dementia Rating, and many of the cognitive domains. The linear regression model showed that the WMH was independently associated with cognitive impairment in patients with PD, regardless of age, sex, duration or severity of PD symptoms, and vascular risk factors. ConclusionsThese findings confirm that WMH might be associated with cognitive decline in patients with PD, regardless of age, sex, education status, duration or severity of PD symptoms, and vascular risk factors. This result suggests that other nonvascular factors contribute to the progression of dementia in patients with PD.

The prevalence and patterns of pharyngoesophageal dysmotility in patients with early stage Parkinson's disease†

Dysphagia occurs in the majority of patients with Parkinsons disease (PD) and is known to correlate with abnormalities of oropharyngeal function. The aim of this study was to evaluate pharyngoesophageal activity in patients with early‐stage PD. Newly diagnosed PD patients with a symptom duration not exceeding 3 years were included. All PD patients were questioned about symptoms of dysphagia and underwent combined multichannel intraluminal impedance manometry and multiple rapid swallow tests. Fifty‐four patients (22 men and 32 women, 67.1 ± 10.3 years) were enrolled. The duration of Parkinsonian motor symptoms was 11.5 ± 8.8 months, the Hoehn and Yahr stage was 1.6 ± 0.4, and the total Unified Parkinsons Disease Rating Scale was 25.1 ± 18.6. Esophageal manometry in the liquid swallow and viscous swallow tests was abnormal in 22 (40.7%) and 31 (67.4%) patients, respectively. Although manometric abnormalities were more common in patients with more severe dysphagia symptoms, many patients with no or minimal symptoms also had manometric abnormalities. Repetitive deglutition significantly correlated with failed peristalsis and incomplete bolus transit. Abnormal responses to multiple rapid swallow tests were found in 33 out of 54 patients; 29 with incomplete inhibition (repetitive contraction) and 4 with failed peristalsis. These results suggest that the majority of patients with early‐stage PD showed pharyngeal and esophageal dysfunction even before clinical manifestations of dysphagia, which may reflect selective involvement of either the brain stem or the esophageal myenteric plexus in early‐stage PD.

Difference of the hippocampal and white matter microalterations in MCI patients according to the severity of subcortical vascular changes: neuropsychological correlates of diffusion tensor imaging.

OBJECTIVESnMost imaging studies of mild cognitive impairment (MCI) have focused on gray matter alterations, although many MCI patients demonstrate subcortical vascular changes. We investigated the changes of the hippocampal area and various white matter areas in MCI patients with using diffusion tensor imaging (DTI), according to the severity of subcortical vascular changes, and we then correlated the DTI findings with the neuropsychological results.nnnPATIENTS AND METHODSnAmong the 40 MCI patients, the 21 non-vascular MCI (nvMCI) and 19 vascular MCI (vMCI) patients were subdivided according to Erkinjunttis imaging criteria. The mean diffusivity (MD) and fractional anisotropy (FA) were compared in the bilateral temporal, frontal, parietal and occipital white matter regions, as well as in the bilateral hippocampi, centrum semiovale, and the midline genu and splenum of the corpus callosum among the nvMCI and vMCI patients and the 17 controls. The neuropsychological findings were also compared between the subgroups.nnnRESULTSnAll the MCI patients showed decreased FA and increased MD in all the regions except the occipital areas. In the parietal regions and centrum semiovale, the vMCI patients had a greater FA decrease than the nvMCI patients and controls. In the hippocampi, the FA was lowest in the nvMCI patients. The memory function in the nvMCI patients was more impaired than that in the vMCI patients. The vMCI patients showed impairment of the visuospatial and frontal executive functions.nnnCONCLUSIONnWe were able to correlate the microstructural alterations with the neuropsychological findings in the MCI subgroups.

Analysis of cerebral blood flow of subcortical vascular dementia with single photon emission computed tomography: Adaptation of statistical parametric mapping

BACKGROUND AND OBJECTIVESnSubcortical vascular dementia (VaD) is a relatively homogeneous subtype of VaD, but the mechanisms of cognitive dysfunction of subcortical VaD are not fully understood. This study investigates the changes of cerebral blood flow (CBF) in patients with subcortical VaD and the contribution of the white matter hyperintensity (WMHI) and clinical severity to CBF changes.nnnMETHODSn99mTc-ethyl cysteinate dimer single photon emission computed tomography (SPECT) was performed to measure the regional CBF and statistical parametric mapping SPM99 software was applied to automated and objective analysis of the SPECT image data. Twenty-three patients (12 male, 11 female) with mild to moderate dementia who met both the criteria of the DSM-IV and probable and possible NINDS-AIREN for VaD and had subcortical white matter changes and lacunar infarctions in brain MRI were evaluated against 17 normal control subjects (7 male, 10 female). The severity of the WMHI was measured by the semi-quantitative scale method proposed by Mäntyla. The Clinical Dementia Rating scale measured the severity of dementia.nnnRESULTSnSPM analysis of the SPECT image reveals significantly reduced regional CBF in the right thalamus, left caudate nucleus, cingulate, bilateral superior temporal, and left ventral subcallosal gyri in subcortical VaD patients compared to the normal controls (corrected P<0.001). Of four WMHIs, only the deep WMHI was associated with the small CBF reduction in the left superior temporal gyrus (uncorrected P<0.01). The reduction of the CBF according to the severity of dementia was noted in the anterior and posterior association areas (uncorrected P<0.01).nnnCONCLUSIONSnOur study suggests that cognitive dysfunction of subcortical VaD may be related to the reduction of the CBF in the brain areas mentioned, which are probably not associated with the severity of periventricular WMHI and dementia.

Voxel based comparison of glucose metabolism in the differential diagnosis of the multiple system atrophy using statistical parametric mapping

OBJECTIVEnA differential diagnosis of idiopathic parkinsonian disease (IPD) and multiple system atrophy (MSA) is difficult due to their common signs and symptoms. The aim of this 18F-2-fluoro-2 deoxyglucose (18F-FDG) positron emission tomography (PET) study was to compare the regional cerebral glucose metabolism in MSA with that in IPD by statistical parametric mapping (SPM) and image registration.nnnMETHODSnThe 18F-FDG PET images of MSA and IPD patients were assessed by SPM and image registration to determine metabolic patterns that may be useful in differentiating between the two groups. Eleven patients with MSA, eight patients with IPD and 22 healthy controls participated in the study.nnnRESULTSnThe IPD patients were found to have a significant glucose hypometabolism in comparison with the healthy controls in the prefrontal, lateral frontal, and parietotemporal cortices, and the cingulate and caudate areas (p< or =0.01, 100 voxel-level). In patients with MSA, hypometabolism was observed in the putamen, pons, and cerebellum in comparison with the healthy controls and IPD patients.nnnCONCLUSIONnThe voxel-based analysis of 18F-FDG PET images showed detailed differences between IPD and MSA, which may be useful in differentiating the two disease entities, as evidenced by the correlation of glucose metabolism with disease severity and dopamine agonist medication. The mapping analysis of 18F-FDG PET images might be a useful adjunctive method of a differential diagnosis for parkinsonism in a clinical setting.

Diffusion weighted MR imaging of acute Wernicke's encephalopathy

We report a case of Wernickes encephalopathy in which diffusion-weighted MR images demonstrated symmetrical hyperintense lesions in the paraventricular area of the third ventricles and medial thalami. Apparent diffusion coefficient mapping showed isointensity in the aforementioned areas. Diffusion-weighted MR images may provide evidence of vasogenic edema associated with thiamine deficiency, proven in the histopathology of experimental animals. In addition, diffusion-weighted MRI has many advantages over T2 or FLARE-weighted brain MRI in detecting structural and functional abnormalities in Wernickes encephalopathy.

Comparison of regional cerebral blood flow in two subsets of subcortical ischemic vascular dementia: statistical parametric mapping analysis of SPECT.

BACKGROUNDnThe brain imaging criteria for subcortical ischemic vascular dementia (SIVD), as proposed by Erkinjuntti, incorporated two clinical entities, the lacunar state and Binswangers disease. However it has not been proven whether these two subtypes of SIVD have common pathophysiological features. This study investigated the changes of regional cerebral blood flow (CBF) in the two subsets of SIVD to establish whether these two subtypes could be incorporated into the same group for the purpose of conducting clinical trials.nnnMETHODSnTwelve SIVD patients with predominant white matter lesions, 13 patients with predominant lacunar infarctions and 17 controls were evaluated. Single photon emission computed tomography (SPECT) was performed to measure the regional CBF, and statistical parametric mapping (SPM) was applied to the analysis of the SPECT data.nnnRESULTSnThe normalized CBF (nCBF) in the bilateral thalami, the anterior cingulate gyri, the superior temporal gyri, the caudate heads and the left parahippocampal gyrus was significantly decreased in the SIVD patients compared to the controls. This pattern of nCBF reduction was same in both the two subtypes of SIVD patients.nnnCONCLUSIONnOur study suggests that the two subsets of SIVD may have a common nCBF abnormality, and Erkinjunttis criteria offer a solution for researchers to identify the more homogeneous group of vascular dementia patients.

Nighttime Blood Pressure and White Matter Hyperintensities in Patients With Parkinson Disease

Increasing evidence indicates that nocturnal blood pressure level and/or loss of nocturnal blood pressure dips are sensitive markers of cardiovascular morbidity and mortality. Several studies have suggested that blunted heart rate variability and nocturnal decline in heart rate are also associated with target organ damage. These phenomena occur relatively commonly in patients with Parkinson disease (PD); however, few studies have assessed the consequences of these abnormalities in patients with PD. We investigated the influence of circadian changes in blood pressure and heart rate on white matter hyperintensities (WMHs) in patients with PD. The presence of nocturnal hypertension was associated with increased WMH score, and nighttime systolic pressure was closely related with white matter changes. Blunted heart rate variability and nocturnal decline in heart rate were also related to increasing WMH scores. The non-dipping phenomenon did not influence WMHs. These findings suggest that white matter changes are related to circadian autonomic dysfunction, particularly nocturnal hypertension in patients with PD. Therefore, it is important to monitor nocturnal blood pressure status, because modifying these circadian regulatory disturbances can be beneficial to protect against vascular brain damage in patients with PD. (Author correspondence: neuronet@catholic.ac.kr)

Comparison of diffusion tensor imaging and voxel-based morphometry to detect white matter damage in Alzheimer's disease.

Regional atrophy of gray matter (GM) in Alzheimers disease (AD) is well known; however, the relationship between macroscopic and microscopic changes of cerebral white matter (WM) is uncertain. The aim of this study was to investigate the pattern of GM, WM atrophy, and microscopic WM changes in the same individuals with AD. All subjects (10AD and 15 healthy controls [HC]) underwent a MRI scanning at 1.5 T, including a 3-dimensional volumetric scan and diffusion tensor imaging (DTI). We performed statistical parametric mapping (SPM) with DTI to evaluate the patterns of the microscopic WM changes, as well as voxel-based morphometry (VBM) for GM and WM volume changes between patients with AD and HC. GM atrophy was detected, mainly in posterior regions, and WM atrophy was similarly distributed, but less involved on VBM analysis. Unlike WM atrophy on VBM analysis, microscopic WM changes were shown in the medial frontal, orbitofrontal, splenium of the corpus callosum, and cingulum on DTI analysis with SPM. We demonstrated that the pattern of macroscopic WM atrophy was similar to GM atrophy, while microscopic WM changes had a different pattern and distribution. Our findings suggest that WM atrophy may preferentially reflect the secondary changes of GM atrophy, while microscopic WM changes start earlier in frontal areas before GM and WM atrophy can be detected macroscopically.