Bora Yoon

Differences in Microstructural Alterations of the Hippocampus in Alzheimer Disease and Idiopathic Normal Pressure Hydrocephalus: A Diffusion Tensor Imaging Study

BACKGROUND AND PURPOSE: DTI can be used to assess the degradation of WM tracts by measuring the FA and MD. Decreased FA/increased MD values in the AD hippocampus have been reported by many studies. In contrast, only a few studies reported on hydrocephalus by using the DTI technique. In elderly patients with dementia and with dilated ventricles, it is often difficult to differentiate iNPH from AD with visual measurements on MR imaging. The aim of this study was to investigate the changes of microstructural integrity of the hippocampus in iNPH by using DTI and determining whether this method could be a new diagnostic tool to differentiate iNPH from AD. MATERIALS AND METHODS: We recruited 43 participants (15 healthy controls, 15 patients with AD, and 13 patients with iNPH). The FA and MD values were measured by using the region-of-interest method in the hippocampal head, body, and tail on both sides. Clinical history, neurologic examination, and neuropsychological assessment were included. RESULTS: The FA values were the lowest in the patients with AD, the patients with iNPH, and the healthy controls in this order. The MD values were the highest in the same order. These findings were consistent in the 3 subdivisions of the bilateral hippocampal regions. Hippocampal volume was not different between patients with iNPH and AD. CONCLUSIONS: The microstructural alterations of the hippocampus were more sensitive than the volumetric changes in AD and iNPH. DTI analysis might be a useful tool for discriminating AD from iNPH.

Microstructural changes in the hippocampus and posterior cingulate in mild cognitive impairment and Alzheimer’s disease: a diffusion tensor imaging study

Diffusion tensor imaging (DTI) is a sensitive MRI technique in the detection of white matter degeneration. We sought to demonstrate microstructural changes in normal controls, patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) and to determine which DTI parameters could be a reliable tool for the early diagnosis of AD. In total, 90 participants (35 normal, 20 aMCI, 35 AD) were recruited. We included early AD patients with clinical dementia rating scores of 0.5 and 1. The fractional anisotropy and mean diffusivity values, DTI parameter, were measured with the regions of interest method in the bilateral hippocampal body and posterior cingulate. Clinical history, neurological examination, and neuropsychological assessments were conducted. The DTI parameters in the bilateral hippocampus and posterior cingulate in aMCI and AD were different from those in normal controls. No difference was found in DTI parameters of the posterior cingulate between aMCI and AD. However, hippocampal DTI parameters were different between aMCI and AD. Cognitive summary measures were significantly correlated with DTI parameters, especially FA values in the hippocampus. The DTI analysis technique demonstrated significant microstructural alterations in the hippocampus and posterior cingulate already in prodromal stage of AD. DTI parameters in the hippocampus may be a more sensitive method to determine microstructural changes in early AD states and more correlated with cognition than DTI parameters in the posterior cingulate.

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.

Effect of literacy and education on the visuoconstructional ability of non-demented elderly individuals.

Learning to read and to write influences not only verbal skills but also global cognitive performance. Our study aimed to compare the visuoconstructional abilities of elderly illiterates with those of elderly literates. A total of 125 healthy subjects over 65 years old were recruited. Korean version of Mini-Mental State Examination (K-MMSE) and the Alzheimers Disease Assessment Scale-cognitive subscale (ADAS-cog) constructional praxis examination were used. We divided subjects into three groups (educated literate n = 53, uneducated literate n = 36 and uneducated illiterate n = 36). Interlocking pentagons drawing, a part of the K-MMSE, was scored using the 6-point hierarchical scale. The uneducated-illiterate group obtained significantly lower scores than did the other two groups. Scores on the ADAS-cog constructional praxis test were highest in the educated-literate group and those in the uneducated-illiterate group obtained the lowest scores. We demonstrated that illiteracy influences not only language performance but also visuoconstructional functioning.

Pattern of Voiding Dysfunction after Acute Brainstem Infarction

Background: The purpose of this study is to compare the patterns of voiding dysfunction according to the locations of brainstem lesions. Methods: Between November 2008 and December 2011, a total of 30 patients participated in this study. All 30 subjects, consisting of 16 men and 14 women, aged between 41 and 82 years (mean age, 63.0 ± 11.0 years) underwent a urodynamic study within 7 days after the onset of a stroke. Results: Twenty-one (70%) patients had a pontine lesion and 9 (30%) had a medullary lesion. Fourteen of these patients (46.7%) had bladder storage disorder, 7 patients (23.3%) had bladder emptying disorder, and 9 patients (30%) had a normal report. Five of the patients who had a medullary lesion (55.6%) had bladder emptying disorder, whereas only 2 patients who had a pontine lesion (9.5%) had bladder emptying disorder. Thirteen patients who had a pontine lesion (61.9%) showed bladder storage disorder. Discussion: The descending pathway from the midbrain tegmentum is inhibitory, and the pathway from the pontine tegmentum is stimulatory. Because of their location pontine lesions could disrupt the descending fibers of the midbrain tegmentum and medullary lesions could disrupt the descending fibers of the pontine tegmentum.

Early Pathological Changes in the Cerebellum of Patients with Pure Cerebellar Syndrome Demonstrated by Diffusion-Tensor Imaging

We evaluated the early pathological changes in patients with sporadic cerebellar ataxia by measuring fractional anisotropy (FA) values in diffusion tensor MRIs (DTI). FA and apparent diffusion coefficient (ADC) values were compared in the brain stem and cerebellum of 5 patients with idiopathic cerebellar ataxia-C and 7 age-matched controls. Patients with sporadic cerebellar ataxia had decreased FA values in the bilateral cerebellar peduncle and cerebellar hemisphere, but normal FA values in the basis pontes. Assuming that the loss in FA parallels neuronal changes, our results suggest that the derangement and altered fiber integrity of the cerebellum are present regardless of the presence of morphological alterations on conventional MRI. Therefore, DTI may be superior to conventional MRI in the evaluation of early pathological changes in patients with sporadic cerebellar ataxia.

Default Mode Network Functional Connectivity in Early and Late Mild Cognitive Impairment Results From the Alzheimer's Disease Neuroimaging Initiative

Background:Default mode network (DMN) functional connectivity is one of the neuroimaging candidate biomarkers of Alzheimer disease. However, no studies have investigated DMN connectivity at different stages of mild cognitive impairment (MCI). The aim of this study was to investigate patterns of DMN connectivity and its breakdown among cognitively normal (CN), early MCI (EMCI), and late MCI (LMCI) subjects. Methods:Magnetic resonance imaging data and neuropsychological test scores from 130 subjects (CN=43, EMCI=47, LMCI=40) were obtained from the Alzheimer’s Disease Neuroimaging Initiative. DMN functional connectivity was extracted using independent components analysis and compared between groups. Results:Functional connectivity in the precuneus, bilateral medial frontal, parahippocampal, middle temporal, right superior temporal, and left angular gyri was decreased in EMCI subjects compared with CN subjects. When the 2 MCI groups were directly compared, LMCI subjects exhibited decreased functional connectivity in the precuneus, bilateral medial frontal gyri, and left angular gyrus. There was no significant difference in gray matter volume among the 3 groups. Amyloid-positive EMCI subjects revealed more widespread breakdown of DMN connectivity than amyloid-negative EMCI subjects. A quantitative index of DMN connectivity correlated well with measures of cognitive performance. Conclusions:Our results suggest that the breakdown of DMN connectivity may occur in the early stage of MCI.

Hippocampal and entorhinal structures in subjective memory impairment: a combined MRI volumetric and DTI study

BACKGROUND Subjective memory impairment (SMI) is common among older adults. Increasing evidence suggests that SMI is a risk factor for future cognitive decline, as well as for mild cognitive impairment and dementia. Medial temporal lobe structures, including the hippocampus and entorhinal cortex, are affected in the early stages of Alzheimers disease. The current study examined the gray matter (GM) volume and microstructural changes of hippocampal and entorhinal regions in individuals with SMI, compared with elderly control participants without memory complaints. METHODS A total of 45 participants (mean age: 70.31 ± 6.07 years) took part in the study, including 18 participants with SMI and 27 elderly controls without memory complaints. We compared the GM volume and diffusion tensor imaging (DTI) measures in the hippocampal and entorhinal regions between SMI and control groups. RESULTS Individuals with SMI had lower entorhinal cortical volumes than control participants, but no differences in hippocampal volume were found between groups. In addition, SMI patients exhibited DTI changes (lower fractional anisotropy (FA) and higher mean diffusivity in SMI) in the hippocampal body and entorhinal white matter compared with controls. Combining entorhinal cortical volume and FA in the hippocampal body improved the accuracy of classification between SMI and control groups. CONCLUSIONS These findings suggest that the entorhinal region exhibits macrostructural as well as microstructural changes in individuals with SMI, whereas the hippocampus exhibits only microstructural alterations.

Cognitive Profiles and Neuropsychiatric Symptoms in Korean Early-Onset Alzheimer's Disease Patients: A CREDOS Study

BACKGROUND & OBJECTIVE Early-onset Alzheimers disease (EOAD, onset age < 65 years) may differ from late-onset Alzheimers disease (LOAD) in terms of cognitive profiles and neuropsychiatric symptoms. There have been few studies for Korean EOAD patients using well-structured databases. Previous studies focusing on cognitive profiles between the two groups had a variety of demographic data and comparability. The purpose of this study was to identify the unique profiles of cognitive functions and neuropsychiatric symptoms in Korean EOAD patients that differentiate from LOAD. METHODS Through propensity score matching, a total of 435 patients with EOAD and a total of 435 patients with LOAD were included in this nationwide, multicenter, hospital-based study. Each patient underwent comprehensive neurological examination, interview for caregiver, neuropsychological tests, and brain magnetic resonance imaging. RESULTS Neuropsychological test results showed worse performances on frontal/executive functions, visuospatial function, and visual memory in EOAD patients as compared to LOAD patients. In terms of neuropsychiatric symptoms, apathy was more common in EOAD patients, while delusions were more prevalent in LOAD patients. The differences in neuropsychiatric symptoms between the two groups were most pronounced in patients with the APOE ε4 allele, suggesting that neuropsychiatric symptoms in AD may be influenced by the APOE genotype. CONCLUSION Our results suggested that EOAD may be an important phenotype, fronto-parietal dysfunction, in the spectrum of AD, and this finding can provide for early diagnosis of EOAD patients.

Do Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD) progress differently?

Our study aimed to compare cognitive status and declines in AD with/without small vessel disease (SVD) and SIVD at baseline and 1-year follow-up. Patients with Alzheimers disease without small vessel disease (AD(-)SVD) (n=148), Alzheimers disease with small vessel disease (AD(+)SVD) (n=94) and SIVD (n=60) were recruited from database of multiple centers in Korea. Basic demographics and detailed neuropsychological results were compared. AD, regardless of SVD, showed worse memory and better executive function than SIVD at baseline. Mini-Mental State Examination scores and visual memory function declined more in AD than those in SIVD whereas Barthel Activities of Daily Living (B-ADL) scores declined more in SIVD. AD showed different patterns of cognitive impairment compared with SIVD. After 1 year, AD showed more rapid cognitive decline in some domains. Further investigations with longer follow-up duration may be needed to confirm the cumulative effects of SVD in AD and different patterns of decline between AD and SIVD.