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.

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.

A randomized phase III trial of stereotactic radiosurgery (SRS) versus observation for patients with asymptomatic cerebral oligo-metastases in non-small-cell lung cancer.

BACKGROUND: It is unclear whether treating brain metastasis before starting systemic chemotherapy can improve survival compared with upfront chemotherapy in non-small-cell lung cancer (NSCLC) with asymptomatic cerebral oligo-metastases. PATIENTS AND METHODS: We undertook a randomized, controlled trial of 105 patients with one to four brain metastases, admitted to Samsung Medical Center between 2008 and 2013. Patients were randomly assigned to receive stereotactic radiosurgery (SRS) (49 patients) followed by chemotherapy or upfront chemotherapy (49 patients). The primary end point was overall survival (OS) and secondary end points included central nervous system (CNS) progression-free survival, progression to symptomatic brain metastasis and brain functional outcome. RESULTS: The median age was 58 years (range, 29-85) with ECOG 0-1 performance status, and 40% of patients were never smokers. Most patients had adenocarcinoma, and about half of patients had only one brain metastasis, while the rest had multiple cerebral metastases. The median OS time was 14.6 months [95% confidence interval (CI), 9.2-20.0] in the SRS group and 15.3 months (95% CI, 7.2-23.4) for the upfront chemotherapy group (P = 0.418). There was no significant difference in time to CNS disease progression [median, 9.4 months (SRS) versus 6.6 months (upfront chemotherapy), P = 0.248]. Symptomatic progression of brain metastases was observed more frequently in the upfront chemotherapy group (26.5%) than the SRS group (18.4%) but without statistical significance. CONCLUSIONS: Although this study included smaller sample size than initially anticipated due to early termination, SRS followed by chemotherapy did not improve OS in oligo-brain metastases NSCLC patients compared with upfront chemotherapy. Further study with large number of patients should be needed to confirm the use of upfront chemotherapy alone in this subgroup of patients. CLINICAL TRIALS NUMBER: NCT01301560.

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.

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.

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.

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.

Paradoxical embolism as a cause of silent brain infarctions in healthy subjects: the ICONS study (Identification of the Cause of Silent Cerebral Infarction in Healthy Subjects).

BACKGROUND: In healthy elderly people, silent brain infarctions (SBIs) have been recognized as common lesions. In this study, we evaluated the association between SBI located outside the perforating artery territory (PAT) and paradoxical embolism detected by agitated saline transcranial Doppler (TCD) monitoring in healthy subjects. METHODS: This was a prospective observational study undertaken by a university health promotion center for healthy subjects and by a university stroke center for acute stroke patients. We defined SBI as evidence on fluid-attenuation inversion recovery (FLAIR) magnetic resonance imaging (MRI) of one or more infarcts, without history of corresponding stroke or transient ischaemic attack. We also evaluated in all subjects the neuroimaging indicator of microangiopathy leukoaraiosis (LA). This study is registered with ClinicalTrials.gov, number NCT01429948. RESULTS: Amongst 1103 consecutive healthy adults who underwent MRI, 347 (31%) had one or more SBIs located outside the PAT, suggesting embolism. Amongst them, 253 subjects underwent agitated saline TCD monitoring and 128 (51%) had right-to-left shunts (RLS). The prevalence of RLS was similar to cryptogenic embolic stroke (62.0%, P = 0.056), but higher than in patients with other stroke subtypes (36.2%, P = 0.021). Amongst subjects with SBI, absence of LA was the only factor associated with RLS (OR 1.78; 95% CI 1.01-3.14; P = 0.046). CONCLUSION: Our results suggest that paradoxical embolism may play an important role in the development of SBI outside the PAT in apparently healthy adults.

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.

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.

Slow vertical saccades in the frontotemporal dementia with motor neuron disease.

BACKGROUND: Ocular motor abnormalities play an important role in differential diagnoses of Pick complex diseases. OBJECTIVES: We evaluated how frequently supranuclear vertical saccadic impairment was observed in patients with frontotemporal dementia with motor neuron disease (FTD-MND). In addition, we tried to characterize their vertical saccadic abnormalities. MATERIALS AND METHODS: Eleven patients with FTD-MND were recruited. Supranuclear vertical saccadic impairment on gross examination was defined as slow saccades with or without reduction in the final amplitude of the movement accompanied by intact oculocephalic reflex. We also recorded their saccades in 6 out of 11 patients using 2-dimensional videooculography (VOG). We measured the amplitude and peak velocity of each saccade. RESULTS: On bedside examination, supranuclear vertical saccadic impairment was observed in 9 of 11 patients. One of the two remaining patients could not be evaluated due to poor cooperation and the other showed normal saccades. Five of nine patients with ocular abnormalities and one patient with normal saccade on gross examination underwent the VOG studies. The results showed that all the five patients with gross ocular abnormalities, compared with age-matched controls, had slowing of vertical saccades. Three out of five patients also showed slowing even in the large horizontal saccades. CONCLUSIONS: Our results showed that slow vertical saccades are common in FTDMND. FTD-MND could be another disease that affects vertical gaze among Pick complex disease. Future pathologic studies are needed to confirm the involvement of the burst neurons in the dorsal midbrain in patients with FTDMND.

Hemispatial neglect in cerebellar stroke.

Cognitive deficits can be associated with cerebellar injury. The purpose of this study is to learn 1) if unilateral cerebellar injury might also cause hemispatial neglect, and if so, 2) if there is a left versus right asymmetry, 3) if the neglect is contralesional (CN) or ipsilesional (IN), and 4) if cerebellar injury might induce neglect by disruption of cerebellar-cortical networks. Participants were 28 patients with unilateral cerebellar stroke who were assessed for neglect within 2 months after the onset of stroke. To investigate if the cerebellar-cerebral network dysfunction induced neglect, 12 patients received perfusion single photon emission computed tomography (SPECT). Eight of the participants demonstrated neglect (28.6%), four with left cerebellar strokes (three with CN and one with IN) and four with right cerebellar strokes (three with IN and one with CN). Among five patients with neglect who had undergone SPECT, only one with ipsilesional neglect showed crossed cerebello-cerebral diaschisis. Neglect induced by cerebellar stroke might be more common than previously reported. Based on the cerebellar-cerebral network hypothesis we expected neglect to be more common with left than right cerebellar injury, but there was an equal number of patients with neglect from right and left sided strokes and the SPECT scan did not provide support of this hypothesis. Thus, this hypothesis cannot also explain the equal number of subject with ipsi- and contralesional neglect and in future studies alternative hypotheses such as vestibular hypothesis will have to be explored.

Glucose metabolism in early onset versus late onset Alzheimer's disease: an SPM analysis of 120 patients.

The aims of this cross-sectional study were (i) to compare the overall glucose metabolism between early onset and late onset Alzheimer's disease in a large sample of patients; and (ii) to investigate the pattern of glucose metabolism as a function of dementia severity in early onset versus late onset Alzheimer's disease, using a statistical parametric mapping (SPM) analysis. Subjects consisted of four groups: 74 patients with early onset Alzheimer's disease, 46 patients with late onset of the disease, and two control groups age matched to each patient group. All the subjects underwent 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG)-PET under the same scanning conditions. Severity of dementia was rated with the Clincial Dementia Rating (CDR). Voxel-based SPM99 was used for statistical analyses. Overall glucose hypometabolism of early onset Alzheimer's disease patients was much greater in magnitude and extent than that of late onset patients, though both groups were similar in dementia severity: the early onset group showed more severe hypometabolism in parietal, frontal and subcortical (basal ganglia and thalamus) areas. When the decline of glucose metabolism was compared as a function of CDR stage, the slope was steeper in early onset than in late onset Alzheimer's disease. The rapid decline occurred at CDR 0.5-1 in the early onset group, whereas similar changes occurred at CDR 2-3 in the late onset group. The greater hypometabolism in early onset than in late onset patients is required to reach the same severity of dementia, probably reflecting greater functional reserve in younger than in older subjects. Alternatively, the metabolic decline curve suggests that the early onset patients may take a more rapid course in the reduction of glucose metabolism than the late onset patients.

Correlation of ventricular asymmetry with metabolic asymmetry in frontotemporal dementia.

BACKGROUND AND PURPOSE: The clinical presentation of frontotemporal dementia (FTD) is often asymmetrical in terms of both its clinical features and atrophy on MRI. Asymmetry in the lateral ventricle size on structural neuroimaging in FTD patients may have clinical significance. However, this has not been systematically investigated yet. This study compares the ventricular asymmetry seen on MRI with that of the asymmetric glucose metabolism using FDG-PET in patients with FTD. METHODS: Nineteen FTD patients who underwent both brain MRI and FDG-PET were retrospectively selected. As control groups, 23 and 11 age and sex-matched healthy normal subjects underwent either brain MRI or FDG-PET, respectively. The ventricular asymmetry index (VAI) was obtained in two ways: by visual rating (VAI-V) and by measuring the lateral ventricular volumes (VAI-ROI). The hemispheric asymmetry of the glucose metabolism on FDG-PET (MAI) was assessed in three ways: 1) by visual rating (MAI-V), 2) by counting the FDG activity of each hemisphere on normalized and smoothed PET images (MAI-ROI) and 3) by counting the number of voxels with significant hypometabolism based on statistical parametric mapping results (MAI-SPM). RESULTS: The VAIs on MRI (VAI-V and VAI-ROI) were highly correlated, as were the MAIs (MAI-V, MAI-ROI, and MAI-SPM) on FDG-PET. More importantly, the VAIs on MRI and the MAIs on FDG-PET showed high correlation. CONCLUSIONS: Ventricular asymmetry in FTD patients was common (78.9%) and there was a high correlation between the ventricular structural asymmetry and the hemispheric metabolic asymmetry. Therefore, it would be reasonable to interpret that the hemisphere with larger ventricle on MRI in FTD patients is undergoing a more active degenerative process.

Diffusion-weighted magnetic resonance imaging in probable Creutzfeldt-Jakob disease: a clinical-anatomic correlation.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rare transmissible disease that typically causes a rapidly progressive dementia and leads to death in less than 1 year. Although a few anecdotal reports suggest that diffusion-weighted magnetic resonance imaging may help substantiate premortem diagnosis of CJD, detailed correlation between radiographic data and clinical, electrophysiologic, and metabolic parameters is not available. METHODS: Signal abnormalities on diffusion-weighted images in 3 consecutive patients with probable CJD were correlated with psychometric features, electroencephalographic findings, and functional images with either positron emission tomography or single photon emission computed tomography. RESULTS: Focality of abnormalities on diffusion-weighted image, not apparent on routine magnetic resonance images, correlated closely with clinical manifestations of CJD. The topographic distribution of signal abnormality on diffusion-weighted image corresponded with abnormal metabolism or perfusion on positron emission and single photon emission computed tomographic scans. In 2 cases, the laterality of diffusion abnormalities correlated with periodic sharp wave activity on electroencephalograms. CONCLUSION: These findings extend previous observations that suggested a diagnostic and localizing utility of diffusion-weighted imaging in CJD.

A compulsive collecting behavior following an A-com aneurysmal rupture.

Hoarding behavior associated with focal brain injury is rarely reported. The authors report a 46-year-old man with pathologic collecting behavior after a left orbitofrontal and caudate injury from an aneurysmal rupture of anterior communicating artery. His hoarding, an impulse control disorder or an ego-syntonic compulsion, was restricted to one specific item (toy bullet). Treatments with sertraline or fluoxetine were not effective for the hoarding.

Memory deficits after bilateral anterior fornix infarction.

The authors report a patient who suddenly developed memory loss without any other focal neurologic deficits. Neuropsychological testing showed severe anterograde verbal and visual memory deficits that improved gradually over several months, but not to the point of the premorbid state. Brain MRI with diffusion-weighted imaging performed 3 days after onset revealed acute infarction involving the bilateral fornices and the right genu of the corpus callosum. The authors suggest that acute fornix infarction may cause anterograde memory deficits.

Influence of final search direction on tactile line bisection in normal subjects.

BACKGROUND: Many variables influence the tactile bisection performance of normal subjects. Of these, studies that investigated the starting point effect have reported inconsistent results. OBJECTIVE: To determine if the final search direction rather than the initial search direction (starting point) may have an effect on tactile bisection performance, especially when subjects are making multiple searches. METHODS: The authors divided the experiment into single- and multiple-search tasks. Thirty-two blindfolded normal subjects were asked to indicate the midpoint of a rod after a one-way search (single-search task) or after two or more one-way searches (multiple-search task). In each task, the subject started on either end of the horizontally placed rods. The same procedure was also conducted with rods oriented vertically or radially. Therefore, there were six conditions (two starting points x three orientations). RESULTS: In the single-search task, there was a significant effect of starting point or movement direction in all six conditions, with biases occurring toward the starting point from the true midpoint (this is termed the "overshoot phenomenon"). In the multiple-search task, however, there was no significant effect of the starting point in all six conditions. Rather, biases depended on the final movement direction in five of the six conditions, occurring toward the starting point of the final search. CONCLUSION: Future research is needed to understand the mechanism of the overshoot phenomenon in tactile bisection by normal subjects and how the overshoot phenomenon influences patients with neglect.

Diffusion-weighted MRI in vascular dementia.

OBJECTIVE: To examine the ability of diffusion-weighted MRI (DWI) to detect ongoing cerebral ischemia in patients with vascular dementia (VaD). BACKGROUND: VaD due to small-vessel disease results from the cumulative impact of recurrent cerebral ischemia. Cerebral ischemia may produce clinical manifestations, producing the "stepwise" decline characteristic of VaD. Conventional MRI can detect small regions of ischemic damage but cannot determine when injury developed. In contrast, DWI shows sensitivity in detecting ischemia of recent onset. DESIGN/METHODS: Patients with VaD (n = 30) underwent DWI in addition to standard MRI sequences. Patients were divided into two groups according to the presence of new focal deficits or mental change within 10 days before MRI. In 10 patients of positive group, symptomatic neurologic decline occurred an average of 4.2 days before the imaging procedure. RESULTS: Seven (70%) of 10 patients with a recent neurologic event showed 15 new regions of signal abnormality on DWI. The anatomic distribution of signal change could account for the patients' new symptoms or signs in all but one patient. Similar signal abnormality was detected in 4 (20%) of 20 patients without a recent neurologic event. New foci of altered signal intensity were distinguishable from prior injuries only with DWI. No significant difference was found between patients with and without DWI abnormalities in gender, age, Mini-Mental State Examination score, Hachinski Ischemic Score, vascular risk factors, or severity of increased signal on T2-weighted MRI scans. CONCLUSION: Small foci of abnormal signal on diffusion-weighted MRI (DWI), presumably representing recent small infarcts, occur often in vascular dementia (VaD) from small-vessel disease, even in patients without a recent "stepwise decline." The results suggest that DWI might be used to monitor VaD progression in future observational and interventional studies of this disorder.