Parahippocampal Atrophy is Associated with Depressive Symptoms in Alzheimer's Disease.

Background Alzheimer's disease (AD) patients frequently show depressive symptoms, yet the pathological background remains unclear. The voxel-based specific regional analysis system for AD (VSRAD) allows quantification of atrophy in the medial temporal structures. We measured the degree of parahippocampal atrophy in AD patients using VSRAD, and investigated the association between imaging analysis results and the severity of depressive symptoms. Methods Brain magnetic resonance imaging (MRI) was conducted in 39 AD outpatients, and all MRI data were analyzed using VSRAD. The target region of interest (ROI) mainly consisted of the parahippocampal gyrus. The degree of atrophy in the ROI was obtained from the averaged positive z score (Z-score) of the ROT. AD patients were divided into two groups based on the severity of their depressive symptoms using the Geriatric Depression Scale (GDS), the depressive group (D group: 20 patients) and non- depressive group (ND group: 19 patients), and the clinical characteristics and VSRAD results of both groups were compared. Results There were no significant differences in demographics or cognitive function between the two groups. The Z-scores of the D group were significantly higher than those of the ND group (p<0.05). Additionally, there was a significant positive correlation between the GDS score and Z-scores in the parahippocampal gyrus. Conclusions Our findings suggested that the severity of depressive symptoms is associated with the severity of parahippocampal atrophy in AD patients.

The Relationship Between Medial Temporal Lobe Atrophy and Cognitive Impairment in Patients With Dementia With Lewy Bodies.

BACKGROUND: The relationship between medial temporal lobe atrophy (MTA) and cognitive impairment in patients with dementia with Lewy bodies (DLB) remains unclear. We examined this relationship using voxel-based specific regional analysis system for Alzheimer disease (VSRAD) advance software, which allowed us to quantify the degree of MTA on images obtained from magnetic resonance imaging (MRI) scans. METHODS: Thirty-seven patients diagnosed with DLB were recruited and scanned with a 1.5 Tesla MRI scanner. All MRI data were analyzed using VSRAD advance. The target volume of interest (VOI) included the entire region of the entorhinal cortex, hippocampus, and amygdala. The degree of MTA was obtained from the averaged positive z-score (Z score) on the target VOI, with higher scores indicating more severe MTA. Mini-Mental State Examination (MMSE) and the Revised Hasegawa Dementia Scale (HDS-R), which strengthened the measures of memory and language more than MMSE, were used to assess the presence of cognitive impairment. RESULTS: A negative correlation was found between the Z score and MMSE total scores or the HDS-R total scores. A stepwise multiple regression analysis performed to adjust the covariate effects of sex, age, the onset age of the disease, duration of DLB, years of education, and donepezil treatment showed that the HDS-R total scores were independently associated with the Z score, whereas MMSE total scores were not. CONCLUSIONS: These results suggest that MTA is related to cognitive impairment in patients with DLB, particularly the regions of orientation, immediate and delayed recall, and word fluency.

Evaluation of therapeutic response to donepezil by positron emission tomography.

BACKGROUND: Donepezil hydrochloride (Donepezil) is an acetylcholinesterase inhibitor (AChEI) that is used for the symptomatic treatment of Dementia of the Alzheimer's Type (DAT). Recently, the effects of AChEI in patients with DAT have been investigated using positron emission tomography (PET) or single photon emission computed tomography (SPECT). This study is to evaluate the usefulness of fluorine-18-fluorodeoxyglucose (FDG)-PET in assessing the therapeutic response of Donepezil to DAT using Regions of Interest (ROI) analysis. METHODS: The participants included eleven outpatients diagnosed as having DAT according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The patients were performed FDG-PET before initiating Donepezil therapy and after 12 weeks of medication. Cognitive change was measured using the Japanese version of the Alzheimer's disease Assessment Scale cognitive subscale (ADAS-J cog) and the group was divided into Responders and Non-responders based on these results. We used FDG-PET to investigate glucose metabolism of the brain and measured FDG uptake in the ROI set in each lobe of the brain. Then the ratios of the post-treatment uptake to pre-treatment uptake were determined. RESULTS: In the Responders, the mean ratios in the frontal, temporal, occipital, parietal, and temporoparietal lobes were 2.18, 1.62, 1.15, 1.12, and 1.09 respectively. The mean ratios of the Non-responders were 0.69, 0.88, 0.75, 0.98, and 0.68 respectively. Significant differences were found between the ratios of the Responders and Non-responders in the frontal and occipital lobes (p < 0.05). CONCLUSIONS: These findings suggest that FDG-PET could be useful for the evaluation for monitoring response to Donepezil.

Frontal hypoperfusion in depressed patients with dementia of Alzheimer type demonstrated on 3DSRT.

AIMS: Depressive symptoms are common in patients with dementia of Alzheimer type (DAT) and contribute to clinical morbidity. Previous studies have suggested that hypoperfusion in the prefrontal cortex and anterior cingulate gyrus are involved in the pathophysiology of depression in DAT. Using 3-D stereotactic region of interest (ROI) template (3DSRT), fully automated ROI analysis software, the purpose of the present study was to investigate the relationship between depressive symptoms and regional cerebral blood flow (rCBF) in DAT. METHODS: Technetium-99m-ethyl cysteinate dimer ((99m)Tc-ECD) single-photon emission computed tomography (SPECT) and Japanese version of the Neuropsychiatric Inventory (NPI) were carried out in 35 patients diagnosed as having mild-moderate DAT according to DSM-IV. These patients were divided into the depressive group (D group: n = 17) and non-depressive group (ND group: n = 18) using the NPI depression items. All data from SPECT images were analyzed using 3DSRT software. On 3DSRT the perfusion ratios (rCBF of bilateral callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus and hippocampus/cerebellar hemisphere) of each segment were compared between the D group and the ND group. RESULTS: The perfusion ratios of the left callosomarginal segment for the D group were significantly lower (P < 0.05) than those of the ND group. CONCLUSIONS: Hypoperfusion in the left frontal cortex contributes to the expression of depressive symptoms in patients with DAT.

The relationship between depressive symptoms and prefrontal hypoperfusion demonstrated by eZIS in patients with DAT.

Depressive symptoms are common in Alzheimer's disease (AD) and contribute to clinical morbidity. Previous studies have suggested that hypoperfusion in the prefrontal cortex and anterior cingulate gyrus are involved in the pathophysiology of depression. Using the easy Z-score imaging system (eZIS), we investigated the relationship between depressive symptoms and prefrontal hypoperfusion in AD. Tc-99m-ethyl cysteinate dimer (Tc-99m-ECD)-single photon emission tomography (SPECT) and Neuropsychiatric Inventory (NPI) were performed in forty-four patients diagnosed as having Dementia of Alzheimer's type (DAT) with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). These patients were divided into the depressive group (D group: n=26) and non-depressive group (ND group: n=18) using NPI depression items. All data from SPECT images were analyzed using eZIS software. Scores in four regions were determined by Z-values; these regions consisted of each side of the prefrontal cortex and anterior cingulate gyrus. The mean scores between the D group and ND group were compared. The mean scores of the left prefrontal cortex in the D group were significantly higher (p<0.0125) than those in the ND group. There were no significant differences in the scores of the right prefrontal cortex and the bilateral anterior cingulate gyrus between these two groups (Mann-Whitney U-test). These findings suggest that hypoperfusion in the left prefrontal area contributes to the expression of depressive symptoms in patients with DAT.

New methods to evaluate intestinal drug absorption mediated by oligopeptide transporter from in vitro study using Caco-2 cells.

The aim of the present work is to develop a convenient and rapid screening system in vitro for intestinal drug absorption mediated by oligopeptide transporter (PepT1). In this study, (1) Transports of cephalexin (CEX) and L-phenylalanine (L-Phe) across Caco-2 monolayers were measured and compared with those of passively transported drugs, (2) Inhibitory effects of various drugs on the transport of [(14)C]glycylsarcosine (Gly-Sar) across Caco-2 monolayers were measured and correlated with their in vivo permeability to rat small intestine, (3) Intracellular pH-change induced by co-transport of drugs with proton into Caco-2 cells was monitored by using Fluorometric Imaging Plate Reader (FLIPR, Molecular Devices Corp.). Concentration-dependent transport was observed in Caco-2 monolayers for CEX and L-Phe, although their permeability was relatively low compared to those of passively transported drugs. Inhibitory effects of various drugs including beta-lactam antibiotics and angiotensin converting enzyme-inhibitors on the transport of Gly-Sar correlated well with their in vivo permeability to rat small intestine. It was demonstrated that CEX, but not cefazolin, induced gradual decrease in the intracellular pH of Caco-2 cells. The degree of intracellular pH-change caused by various drugs showed a sigmoidal or saturable relationship with their permeability to rat small intestine. These in vitro approaches with Caco-2 cells should be useful to evaluate in vivo intestinal permeability of drugs mediated by PepT1, suggesting a possibility of high throughput screening of drug absorption.

Photocatalytic degradation of hexachlorocyclohexane (HCH) by TiO2-pillared fluorine mica.

A significant effect of clay host was observed on the photocatalytic activity of TiO2; TiO2-pillared fluorine mica exhibited two orders of magnitude higher activity than TiO2 and TiO2-pillared montmorillonite for the photocatalytic degradation of gamma-HCH.