Hearing loss is associated with cortical thinning in cognitively normal older adults.

BACKGROUND AND PURPOSE: Hearing loss (HL) is one of the most influential risk factors of dementia in older adults. However, its potential association with neurodegeneration is not well established. The association between HL and cortical thickness in cognitively normal older adults was evaluated. METHODS: In all, 982 cognitively normal older adults (age ≥65 years) were identified from the Health Promotion Center at the Samsung Medical Center from September 2008 to December 2014. The participants underwent pure-tone audiometry and brain magnetic resonance imaging. HL was evaluated according to a four-frequency (0.5, 1, 2, 4 kHz) pure-tone average. Participants were divided into three groups according to pure-tone average (normal hearing ≤15 dB, minimal HL 16-25 dB, mild-to-severe HL >25 dB). Cortical thickness in the HL groups was compared with that of the normal hearing group. RESULTS: In women, right ear HL was associated with cortical thinning: the minimal HL group showed cortical thinning in the left frontal and bilateral occipital areas and the mild-to-severe HL group showed cortical thinning in the bilateral frontal, right temporal and bilateral occipital areas compared to the normal hearing group. In men, there was no significant association between HL on either side and cortical thickness. CONCLUSION: In older women, right ear HL is associated with neurodegeneration even in a cognitively normal state. Therefore, managing HL especially in older women may be an effective strategy for dementia prevention.

Longitudinal cortical thinning and cognitive decline in patients with early- versus late-stage subcortical vascular mild cognitive impairment.

BACKGROUND AND PURPOSE: Biomarker changes in cognitively impaired patients with small vessel disease are largely unknown. The rate of amyloid/lacune progression, cortical thinning and cognitive decline were evaluated in subcortical vascular mild cognitive impairment (svMCI) patients. METHODS: Seventy-two svMCI patients were divided into early stage (ES-svMCI, n = 39) and late stage (LS-svMCI, n = 33) according to their Clinical Dementia Rating Sum of Boxes score. Patients were annually followed up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and underwent a second [11 C] Pittsburgh compound B (PiB) positron emission tomography scan within a mean interval of 32.4 months. RESULTS: There was no difference in the rate of increase in PiB uptake or lacune number between the ES-svMCI and LS-svMCI. However, LS-svMCI showed more rapid cortical thinning and cognitive decline than did the ES-svMCI. CONCLUSIONS: We suggest that, whilst the rate of change in pathological burden did not differ between ES-svMCI and LS-svMCI, cortical thinning and cognitive decline progressed more rapidly in the LS-svMCI.

Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells.

OBJECTIVES: Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells. METHODS: To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines. RESULTS: eIF3b silencing decreased cell viability and induced apoptosis in U2OS cells, and by using gene profiling we discovered that eIF3b silencing also resulted in the upregulation of tumour necrosis factor receptor superfamily member 21 (TNFRSF21). We found that TNFRSF21 overexpression induced cell death in U2OS cells, and we confirmed that eIF3b silencing completely suppressed cell growth in multiple osteosarcoma cell lines. However, eIF3b silencing failed to suppress cell growth completely in normal fibroblast cells. CONCLUSION: Our data led us to conclude that eIF3b may be required for osteosarcoma cell proliferation by regulating TNFRSF21 expression.Cite this article: Y. J. Choi, Y. S. Lee, H. W. Lee, D. M. Shim, S. W. Seo. Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells. Bone Joint Res 2017;6:186-193. DOI: 10.1302/2046-3758.63.BJR-2016-0151.R2.

Diagnostic performance of conventional MRI parameters and apparent diffusion coefficient values in differentiating between benign and malignant soft-tissue tumours.

AIM: To compare the abilities of conventional magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) in differentiating between benign and malignant soft-tissue tumours (STT). MATERIAL AND METHODS: A total of 123 patients with STT who underwent 3 T MRI, including diffusion-weighted imaging (DWI), were retrospectively analysed using variate conventional MRI parameters, ADCmean and ADCmin. RESULTS: For the all-STT group, the correlation between the malignant STT conventional MRI parameters, except deep compartment involvement, compared to those of benign STT were statistically significant with univariate analysis. Maximum diameter of the tumour (p=0.001; odds ratio [OR], 8.97) and ADCmean (p=0.020; OR, 4.30) were independent factors with multivariate analysis. For the non-myxoid non-haemosiderin STT group, signal heterogeneity on axial T1-weighted imaging (T1WI; p=0.017), ADCmean, and ADCmin (p=0.001, p=0.001), showed significant differences with univariate analysis between malignancy and benignity. Signal heterogeneity in axial T1WI (p=0.025; OR, 12.64) and ADCmean (p=0.004; OR, 33.15) were independent factors with multivariate analysis. CONCLUSION: ADC values as well as conventional MRI parameters were useful in differentiating between benign and malignant STT. The ADCmean was the most powerful diagnostic parameter in non-myxoid non-haemosiderin STT.

Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder.

Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients.

Impact of smoking on neurodegeneration and cerebrovascular disease markers in cognitively normal men.

BACKGROUND AND PURPOSE: Smoking is a major risk factor for cognitive decline and dementia. However, the exact pathobiology of smoking remains unknown. The effects of smoking on cortical thickness as a biomarker of neurodegeneration or white matter hyperintensities and lacunes as biomarkers of cerebrovascular burden were concurrently evaluated. METHODS: Our study included 977 cognitively normal men who visited a health promotion centre and underwent medical check-ups, including 3.0 T magnetic resonance imaging. Participants were categorized into never smoker, past smoker or current smoker groups and pack-years and the years of smoking cessation were used as continuous variables. RESULTS: The current smoker group exhibited cortical thinning in frontal and temporo-parietal regions compared with the never smoker group. These effects were particularly prominent in smokers with a high cumulative exposure to smoking in the current smoker group. However, there was no association between smoking and the severity of white matter hyperintensity or number of lacunes. CONCLUSION: Our findings indicate that smoking might impact on neurodegeneration rather than cerebrovascular burdens in cognitively normal men, suggesting that smoking might be an important modifiable risk factor for the development of Alzheimer's disease.

Spray-dried plasma attenuates inflammation and improves pregnancy rate of mated female mice.

Three studies were conducted to test the hypothesis that dietary spray-dried plasma (SDP) might improve pregnancy rate by ameliorating inflammation, using mice in an experimental model that produces a low pregnancy rate. Mated female mice (C57BL/6 strain) were purchased and shipped from a vendor (Bar Harbor, ME) to the university facility (Urbana, IL) on the day the vaginal plug was found (gestation day [GD] 1), arriving at the laboratory on GD 3 after 2 d transport by air and ground. Mice (Exp. 1: n = 250, 16.0 ± 1.2 g BW; Exp. 2: n = 202, 16.2 ± 1.2 g BW; Exp. 3: n = 156, 16.4 ± 1.1 g BW) were housed in individual cages and randomly assigned to dietary treatments (Exp. 1: 0 [CON] and 8% SDP in the diet, ≥ 90 mice/diet; Exp. 2: 0, 1, 2, 4, and 8% SDP in the diet, ≥ 40 mice/diet; Exp. 3: 0, 1, and 8% SDP in the diet, 48 mice/diet) fed from arrival. In Exp. 1 and 2, pregnancy of each mouse was determined on GD 17 based on BW, shape of abdomen, and inspection postmortem, and maternal growth performance from GD 3 to 17 was measured. On GD 19, pregnant mice in Exp. 2 were euthanized to measure number of fetuses and fetal and placental weights. Pregnancy rates in CON were low in both Exp. 1 (11%) and Exp. 2 (7%). The SDP consistently and markedly increased (P < 0.05) pregnancy rates in both Exp. 1 (49%) and Exp. 2 (35-43%) compared with the CON. In Exp. 3, 12 randomly selected mice were euthanized immediately after they arrived as an initial group. From GD 4 to 7, randomly selected mice were also euthanized each day (12 mice/diet). After euthanasia, the abdominal cavity was opened to check pregnancy by uterine inspection and to collect blood and uterus samples for immune measurements. The SDP increased (P < 0.05; 40 vs. 15%) pregnancy rate compared with the CON. Concentrations of indicators of inflammation and stress (uterine TNF-α and IFN-γ, and serum TNF-α, C-reactive protein, and cortisol) were greatest (P < 0.05) and an anti-inflammatory cytokine (TGF-ß1) was lowest (P < 0.05) soon after arrival, on GD 3 or 4. The SDP decreased (P < 0.05) the uterine concentrations of TNF-α and IFN-γ, and serum TNF-α, C-reactive protein, and cortisol, compared with the CON, but increased (P < 0.05) the uterine concentration of TGF-ß1. In conclusion, dietary SDP improves the low pregnancy rates in this model, apparently by attenuating inflammation.

White matter microstructural changes in pure Alzheimer's disease and subcortical vascular dementia.

BACKGROUND AND PURPOSE: Recent studies have demonstrated that Alzheimer's disease (AD) and subcortical vascular dementia (SVaD) have white matter (WM) microstructural changes. However, previous studies on AD and SVaD rarely eliminated the confounding effects of patients with mixed Alzheimer's and cerebrovascular disease pathologies. Therefore, our aim was to evaluate the divergent topography of WM microstructural changes in patients with pure AD and SVaD. METHODS: Patients who were clinically diagnosed with AD and SVaD were prospectively recruited. Forty AD patients who were Pittsburgh compound B (PiB) positive [PiB(+) AD] without WM hyperintensities and 32 SVaD patients who were PiB negative [PiB(-) SVaD] were chosen. Fifty-six cognitively normal individuals were also recruited (NC). Tract-based spatial statistics of diffuse tensor imaging were used to compare patterns of fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: Compared with the NC group, the PiB(+) AD group showed decreased FA in the bilateral frontal, temporal and parietal WM regions and the genu and splenium of the corpus callosum as well as increased MD in the left frontal and temporal WM region. PiB(-) SVaD patients showed decreased FA and increased MD in all WM regions. Direct comparison between PiB(+) AD and PiB(-) SVaD groups showed that the PiB(-) SVaD group had decreased FA across all WM regions and increased MD in all WM regions except occipital regions. CONCLUSION: Our findings suggest that pure AD and pure SVaD have divergent topography of WM microstructural changes including normal appearing WM.

Higher C-peptide levels are associated with regional cortical thinning in 1093 cognitively normal subjects.

BACKGROUND AND PURPOSE: Recent studies have demonstrated an association between increased insulin secretion and cognitive impairment. However, there is no previous study that directly evaluates the association between increased insulin secretion and cortical thickness to our knowledge. Therefore, our aim was to evaluate the effect of hyperinsulinemia, as measured by C-peptide level, on cortical thickness in a large sample of cognitively normal individuals. METHODS: Cortical thickness was measured in 1093 patients who visited the Samsung Medical Health Promotion Center and underwent brain magnetic resonance imaging (MRI) and a blood test to measure C-peptide concentration. Automated surface-based analyses of the MRI data were used to measure cortical thickness. C-peptide levels were divided into quartiles for comparison. Patients in the first to third quartiles were used as the reference category. RESULTS: Patients in the highest quartile group (Q4) of C-peptide levels showed cortical thinning, predominantly in both medial temporal lobes, the right inferior temporal gyrus, both medial prefrontal lobes and the right superior parietal lobule, compared with the lower quartile groups (Q1-Q3) after controlling for age, gender, body mass index, history of hypertension, hyperlipidemia, previous stroke, cardiovascular disease and fasting glucose level. CONCLUSIONS: A higher C-peptide level is associated with regional cortical thinning, even in cognitively normal individuals.

Cortical thickness and hippocampal shape in pure vascular mild cognitive impairment and dementia of subcortical type.

BACKGROUND AND PURPOSE: The progression pattern of brain structural changes in patients with isolated cerebrovascular disease (CVD) remains unclear. To investigate the role of isolated CVD in cognitive impairment patients, patterns of cortical thinning and hippocampal atrophy in pure subcortical vascular mild cognitive impairment (svMCI) and pure subcortical vascular dementia (SVaD) patients were characterized. METHODS: Forty-five patients with svMCI and 46 patients with SVaD who were negative on Pittsburgh compound B (PiB) positron emission tomography imaging and 75 individuals with normal cognition (NC) were recruited. RESULTS: Compared with NC, patients with PiB(-) svMCI exhibited frontal, language and retrieval type memory dysfunctions, which in patients with PiB(-) SVaD were further impaired and accompanied by visuospatial and recognition memory dysfunctions. Compared with NC, patients with PiB(-) svMCI exhibited cortical thinning in the frontal, perisylvian, basal temporal and posterior cingulate regions. This atrophy was more prominent and extended further toward the lateral parietal and medial temporal regions in patients with PiB(-) SVaD. Compared with NC subjects, patients with PiB(-) svMCI exhibited hippocampal shape deformities in the lateral body, whilst patients with PiB(-) SVaD exhibited additional deformities within the lateral head and inferior body. CONCLUSIONS: Our findings suggest that patients with CVD in the absence of Alzheimer's disease pathology can be demented, showing cognitive impairment in multiple domains, which is consistent with the topography of cortical thinning and hippocampal shape deformity.

Comparison of cortical thickness in patients with early-stage versus late-stage amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: Disappointing outcomes from clinical trials involving amyloid-modifying therapies for Alzheimer's disease (AD) have prompted more focus on the concept of early-stage (E) amnestic mild cognitive impairment (E-aMCI). However, limited evidence suggests that E-aMCI may represent aMCI at a very early stage of AD. Furthermore, the nature of the progression of E-aMCI to late-stage aMCI (L-aMCI) remains unclear. Therefore, the aim of the present study was to characterize patterns of cortical thinning in both E-aMCI and L-aMCI patients. METHODS: Cortical thicknesses were measured in 190 patients with aMCI and 147 subjects with normal cognition. In accordance with memory test scores involving delayed recall items, aMCI patients were divided into two subgroups, containing 73 E-aMCI subjects with milder memory impairment [scores between -1.5 standard deviation (SD) and -1.0 SD compared with age- and education-matched norms] and 117 L-aMCI subjects with more severe memory impairment (scores lower than -1.5 SD). RESULTS: Compared with controls, the E-aMCI group exhibited cortical thinning in the left medial temporal and insular regions, whereas the L-aMCI group showed cortical thinning in widespread regions, including the bilateral dorsolateral prefrontal, anterior and medial temporal, and temporo-parietal association cortices, and the precuneus. When the two aMCI groups were directly compared, the L-aMCI group showed greater cortical thinning in the right superior prefrontal, medial temporal, posterior cingulate and lateral parietal cortices. CONCLUSION: Our findings suggest that E-aMCI might represent an early symptomatic stage of AD. Furthermore, L-aMCI might resemble AD more closely than E-aMCI, in terms of the topography of cortical thinning.

The accuracy of current methods in determining the timing of epiphysiodesis.

We compared the accuracy of the growth remaining method of assessing leg-length discrepancy (LLD) with the straight-line graph method, the multiplier method and their variants. We retrospectively reviewed the records of 44 patients treated by percutaneous epiphysiodesis for LLD. All were followed up until maturity. We used the modified Green-Anderson growth-remaining method (Method 1) to plan the timing of epiphysiodesis. Then we presumed that the other four methods described below were used pre-operatively for calculating the timing of epiphysiodesis. We then assumed that these four methods were used pre-operatively. Method 2 was the original Green-Anderson growth-remaining method; Method 3, Paley's multiplier method using bone age; Method 4, Paley's multiplier method using chronological age; and Method 5, Moseley's straight-line graph method. We compared 'Expected LLD at maturity with surgery' with 'Final LLD at maturity with surgery' for each method. Statistical analysis revealed that 'Expected LLD at maturity with surgery' was significantly different from 'Final LLD at maturity with surgery'. Method 2 was the most accurate. There was a significant correlation between 'Expected LLD at maturity with surgery' and 'Final LLD at maturity with surgery', the greatest correlation being with Method 2. Generally all the methods generated an overcorrected value. No method generates the precise 'Expected LLD at maturity with surgery'. It is essential that an analysis of the pattern of growth is taken into account when predicting final LLD. As many additional data as possible are required.

Risk factors for post-operative venous thromboembolism in patients with a malignancy of the lower limb.

It is important to be able to identify patients with an increased risk of venous thromboembolism (VTE) in order to minimise the risk of an event. We investigated the incidence and risk factors for post-operative VTE in 168 consecutive patients with a malignancy of the lower limb. The period of study included ten months before and 12 months after the introduction of chemical thromboprophylaxis. All data about the potential risk factors were identified and classified into three groups (patient-, surgery- and tumour-related). The outcome measure was a thromboembolic event within 90 days of surgery. Of the 168 patients, eight (4.8%) had a confirmed symptomatic deep-vein thrombosis and one (0.6%) a fatal pulmonary embolism. Of the 28 variables tested, age > 60 years, higher American Society of Anesthesiologists grade and metastatic tumour were independent risk factors for VTE. The overall rate of symptomatic VTE was not significantly different between patients who received chemical thromboprophylaxis and those who did not. Knowledge of these risk factors may be of value in improving the surgical outcome of patients with a malignancy of the lower limb.

Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-ß plaques.

Presently, co-culture of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) with BV2 microglia under amyloid-ß42 (Aß42) exposure induced a reduction of Aß42 in the medium as well as an overexpression of the Aß-degrading enzyme neprilysin (NEP) in microglia. Cytokine array examinations of co-cultured media revealed elevated release of soluble intracellular adhesion molecule-1 (sICAM-1) from hUCB-MSCs. Administration of human recombinant ICAM-1 in BV2 cells and wild-type mice brains induced NEP expression in time- and dose-dependent manners. In co-culturing with BV2 cells under Aß42 exposure, knockdown of ICAM-1 expression on hUCB-MSCs by small interfering RNA (siRNA) abolished the induction of NEP in BV2 cells as well as reduction of added Aß42 in the co-cultured media. By contrast, siRNA-mediated inhibition of the sICAM-1 receptor, lymphocyte function-associated antigen-1 (LFA-1), on BV2 cells reduced NEP expression by ICAM-1 exposure. When hUCB-MSCs were transplanted into the hippocampus of a 10-month-old transgenic mouse model of Alzheimer's disease for 10, 20, or 40 days, NEP expression was increased in the mice brains. Moreover, Aß42 plaques in the hippocampus and other regions were decreased by active migration of hUCB-MSCs toward Aß deposits. These data suggest that hUCB-MSC-derived sICAM-1 decreases Aß plaques by inducing NEP expression in microglia through the sICAM-1/LFA-1 signaling pathway.

Glucose metabolism in sporadic Creutzfeldt-Jakob disease: a statistical parametric mapping analysis of (18) F-FDG PET.

BACKGROUND AND PURPOSE: Reports describing functional neuroimaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), in sporadic Creutzfeldt-Jakob disease (sCJD) have consistently suggested that these tools are sensitive for the identification of areas of hypoperfusion or hypometabolism, even in the early stages of sCJD. However, there are few reports on the use of [18F]fluoro-2-deoxy-D-glucose (FDG) PET in sCJD, and most of them are single case reports. Only two small cohort studies based on visual inspection or a region of interest method have been published to date. Using a statistical parametric mapping (SPM) analysis of (18) F-FDG PET, we investigated whether there are brain regions preferentially affected in sCJD. METHODS: After controlling for age and gender, using SPM 2, we compared the glucose metabolism between (i) 11 patients with sCJD and 35 controls and (ii) the subset of five patients with the Heidenhain variant of sCJD and 35 controls. RESULTS: The patients with sCJD showed decreased glucose metabolism in bilateral parietal, frontal and occipital cortices. The Heidenhain variant of sCJD showed glucose hypometabolism mainly in bilateral occipital areas. CONCLUSIONS: Glucose hypometabolism in sCJD was detected in extensive cortical regions; however, it was not found in the basal ganglia or thalamus, which are frequently reported to be affected on diffusion-weighted images. The medial temporal area, which is possibly resistant to the prion deposits, was also less involved in sCJD.

Differential diagnosis of idiopathic normal pressure hydrocephalus from other dementias using diffusion tensor imaging.

BACKGROUND AND PURPOSE: Because DTI can provide good markers of white matter pathology, it could be useful in differentiating white matter changes of INPH from those of other dementias. The aim of this study was, by using DTI, to compare the characteristic white matter changes in INPH with those in AD, subcortical vascular dementia, and healthy control subjects. MATERIALS AND METHODS: Sixteen patients with presurgical INPH, 10 with AD, 10 with subcortical vascular dementia, and 20 healthy control subjects underwent DTI. All patients with INPH showed clinical improvement after shunt surgery, and 9 of them also underwent postshunting DTI. Regions of interest were selected at the periventricular white matter, the anterior limb of the internal capsule, the posterior limb of the internal capsule, the genu and the splenium of the corpus callosum, the superior longitudinal fasciculus, and the inferior longitudinal fasciculus. FA and MD were obtained from each region of interest and were compared among the groups. RESULTS: Presurgical INPH showed significantly higher FA than all the other groups in the posterior limb of the internal capsule, which was decreased after shunt surgery. Presurgical MD of the INPH group was higher than that in the AD and healthy control groups but lower than that in the subcortical vascular dementia group in the anterior periventricular white matter, the anterior limb of the internal capsule, and the superior longitudinal fasciculus. In differentiating INPH, the sensitivity and specificity of FA in the posterior limb of the internal capsule was 87.5% and 95.0%, respectively. CONCLUSIONS: Patients with shunt-responsive INPH showed higher FA in the posterior limb of the internal capsule compared with healthy controls and those in other groups of dementia that was reversible with shunt surgery. With this parameter, shunt-responsive INPH could be distinguished from AD, subcortical vascular dementia, and healthy conditions with high diagnostic accuracy.

Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B.

BACKGROUND: Subcortical vascular dementia (SVaD) is considered the most common type of vascular dementia and often follows a slowly progressive course, simulating Alzheimer disease (AD). Whether the progressive cognitive decline is associated with pure SVaD or concomitant AD remains unknown. The purpose of this study was to determine what proportion of patients with SVaD lack abnormal amyloid imaging, and to examine differences in the clinical or MRI features between subjects with SVaD with cortical amyloid deposition and those without. METHODS: We measured brain amyloid deposition using (11)C-Pittsburgh compound B (PiB) PET in 45 patients (men: women = 19:26; mean age 74.2 ± 7.6 years) with SVaD. They all met DSM-IV criteria for vascular dementia and had severe white matter high signal intensities without territorial infarction or macrohemorrhage on MRI. RESULTS: Thirty-one (68.9%) of 45 patients with SVaD were negative for cortical PiB binding. There was significant difference between (11)C-PiB-positive and (11)C-PiB-negative groups in terms of age (79.5 vs 71.9 years), Mini-Mental State Examination score (18.6 vs 22.6), the number of lacunes (3.9 vs 9.0), and the visual rating scale of hippocampal atrophy (3.1 vs 2.3). The neuropsychological assessments revealed that patients with (11)C-PiB-negative SVaD performed better on the delayed recall of both the verbal and visual memory test than did those with (11)C-PiB-positive scan. CONCLUSION: SVaD without abnormal amyloid imaging was more common than expected. Patients with SVaD with and without abnormal amyloid imaging differed in clinical and MRI features, although there was considerable overlap.

Dominance specific visual extinction associated with callosal disconnection.

Callosal disconnection signs are closely related to asymmetric hemispheric specialization of cognitive functions. Although extinction is more commonly associated with the right parietotemporal lesion, it may occur following lesions of the corpus callosum. After an infarction involving the left splenium, a 58-year-old right-handed man had no disconnection symptoms that had been reported earlier, but showed visual extinction with left or right visual hemifield dominant stimuli. Our results suggest that dominance specific visual extinction might be another disconnection sign associated with splenial lesion.