Rafeeque A. Bhadelia

Relationship Between ApoE, MRI Findings, and Cognitive Function in the Cardiovascular Health Study

BACKGROUND AND PURPOSE We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores. METHODS The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years. RESULTS The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2% for participants without and 20.4% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores. The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]). CONCLUSIONS These results demonstrate that vascular changes on MRI, measures of brain atrophy, ApoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia.

25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services

Background: Vitamin D deficiency has potential adverse effects on neurocognitive health and subcortical function. However, no studies have examined the association between vitamin D status, dementia, and cranial MRI indicators of cerebrovascular disease (CVD). Methods: Cross-sectional investigation of 25-hydroxyvitamin D [25(OH)D], dementia, and MRI measures of CVD in elders receiving home care (aged 65–99 years) from 2003 to 2007. Results: Among 318 participants, the mean age was 73.5 ± 8.1 years, 231 (72.6%) were women, and 109 (34.3%) were black. 25(OH)D concentrations were deficient (<10 ng/mL) in 14.5% and insufficient (10–20 ng/mL) in 44.3% of participants. There were 76 participants (23.9%) with dementia, 41 of which were classified as probable AD. Mean 25(OH)D concentrations were lower in subjects with dementia (16.8 vs 20.0 ng/mL, p < 0.01). There was a higher prevalence of dementia among participants with 25(OH)D insufficiency (≤20 ng/mL) (30.5% vs 14.5%, p < 0.01). 25(OH)D deficiency was associated with increased white matter hyperintensity volume (4.9 vs 2.9 mL, p < 0.01), grade (3.0 vs 2.2, p = 0.04), and prevalence of large vessel infarcts (10.1% vs 6.9%, p < 0.01). After adjustment for age, race, sex, body mass index, and education, 25(OH)D insufficiency (≤20 ng/mL) was associated with more than twice the odds of all-cause dementia (odds ratio [OR] = 2.3, 95% confidence interval [CI] 1.2–4.2), Alzheimer disease (OR = 2.5, 95% CI 1.1–6.1), and stroke (with and without dementia symptoms) (OR = 2.0, 95% CI 1.0–4.0). Conclusions: Vitamin D insufficiency and deficiency was associated with all-cause dementia, Alzheimer disease, stroke (with and without dementia symptoms), and MRI indicators of cerebrovascular disease. These findings suggest a potential vasculoprotective role of vitamin D.

Statins and cognitive function in the elderly The Cardiovascular Health Study

Objective: To examine the association of statin drug use on cognitive and MRI change in older adults. Methods: Participants in the Cardiovascular Health Study, a longitudinal study of people age 65 or older, were classified into three groups determined by whether they were taking statin drugs on a continuous basis, intermittently, or not at all. The untreated group was further divided into categories based on National Cholesterol Education Program recommendations for lipid-lowering treatment. Participants with prevalent or incident clinical TIA or stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or below 80 were excluded. Outcomes examined included rate of change on the 3MS over an average observational period of 7 years, along with changes in MRI white matter grade and measures of atrophy. Results: Three thousand three hundred thirty-four participants had adequate data for analysis. At baseline, the untreated group in which lipid-lowering drug treatment was recommended were slightly older, less likely to be on estrogen replacement, and had higher serum cholesterol and lower 3MS scores than the statin-treated group. The rate of decline on the 3MS was 0.48 point/year less in those taking statins compared with the untreated group for which treatment was recommended (p = 0.069) and 0.49 point/year less in statin users compared with the group in which lipid-lowering treatment was not recommended (p = 0.009). This effect remained after controlling for serum cholesterol levels. One thousand seven hundred thirty participants with baseline 3MS scores of >80 underwent cranial MRI scans on two occasions separated by 5 years. There was no significant difference in white matter grade change or atrophy measures between groups. Conclusion: Statin drug use was associated with a slight reduction in cognitive decline in an elderly population. This relationship could not be completely explained by the effect of statins on lowering of serum cholesterol.

Cerebrospinal fluid pulsation amplitude and its quantitative relationship to cerebral blood flow pulsations : a phase-contrast MR flow imaging study

Abstract Our purpose in this investigation was to explain the heterogeneity in the cerebrospinal fluid (CSF) flow pulsation amplitudes. To this end, we determined the contributions of the cerebral arterial and jugular venous flow pulsations to the amplitude of the CSF pulsation. We examined 21 healthy subjects by cine phase-contrast MRI at the C2–3 disc level to demonstrate the CSF and vascular flows as waveforms. Multiple regression analysis was performed to calculate the contributions of (a) the arterial and venous waveform amplitudes and (b) the delay between the maximum systolic slopes of the arterial and venous waveforms (AV delay), in order to predict the amplitude of the CSF waveform. The contribution of the arterial waveform amplitude was positive (r = 0.61; p = 0.003) to the CSF waveform amplitude and that of the venous waveform amplitude was negative (r = −0.50; p = 0.006). Both in combination accounted for 56 % of the variance in predicting the CSF waveform amplitude (p < 0.0006). The contribution of AV delay was not significant. The results show that the variance in the CSF flow pulsation amplitudes can be explained by concurrent evaluation of the CSF and vascular flows. Improvement in the techniques, and controlled experiments, may allow use of CSF flow pulsation amplitudes for clinical applications in the non-invasive assessment of intracranial dynamics by MRI.

Education and the cognitive decline associated with MRI-defined brain infarct

Objective: To assess whether educational attainment, a correlate of cognitive reserve, predicts the amount of cognitive decline associated with a new brain infarct. Methods: The Cardiovascular Health Study is a population-based, longitudinal study of people aged 65 years and older. Cognitive function was measured annually using the Modified Mini-Mental State Examination (3MS) and the Digit-Symbol Substitution Test (DSST). The authors tested whether education level modified 1) the cross-sectional association between cognitive performance and MRI-defined infarct and 2) the change in cognitive function associated with an incident infarct at a follow-up MRI. Results: In cross-sectional analysis (n = 3,660), MRI-defined infarct was associated with a greater impact on 3MS performance in the lowest education quartile when compared with others (p for heterogeneity = 0.012). Among those with a follow-up MRI who had no infarct on initial MRI (n = 1,433), education level was not associated with the incidence, size, or location of new brain infarct. However, a new MRI-defined infarct predicted substantially greater decline in 3MS scores in the lowest education group compared with the others (6.3, 95% CI 4.4- to 8.2-point decline vs 1.7, 95% CI 0.7- to 2.7-point decline; p for heterogeneity < 0.001). Higher education was not associated with smaller declines in DSST performance in the setting of MRI-defined infarct. Conclusions: Education seems to modify an individuals decline on a test of general cognitive function when there is incident brain infarct. These findings are consistent with the hypothesis that cognitive reserve influences the impact of vascular injury in the brain.

Functional analysis of third ventriculostomy patency with phase-contrast MRI velocity measurements

Abstract Our purpose was to explore the utility of cine phase-contrast MRI velocity measurements in determining the functional status of third ventriculostomies, and to correlate the quantitative velocity data with clinical follow-up. We examined six patients with third ventriculostomies and 12 normal subjects by phase-contrast MRI. The maximum craniocaudal to maximum caudocranial velocity range was measured at regions of interest near the third ventricular floor, and in cerebrospinal fluid anterior to the upper pons and spinal cord on midline sagittal images. Ratios of the velocities of both the third ventricle and prepontine space to the space anterior to the spinal cord were obtained. The velocities near the third ventricular floor and in the pontine cistern were significantly higher in patients than in normal subjects, but the velocity anterior to the spinal cord was similar between the groups. The velocity ratios, used to normalize individual differences, were also higher in patients than in controls. Two patients had lower velocity ratios than their fellows at the third ventricular floor and in the pontine cistern; one required a shunt 11 months later, while in the other, who had a third ventricular/thalamic tumor, the lower values probably reflect distortion of the third ventricular floor. We conclude that phase-contrast MR velocity measurements, specifically the velocity ratio between the high pontine cistern and the space anterior to the spinal cord, can help determine the functional status of third ventriculostomies.

Anatomic Brain Disease in Hemodialysis Patients: A Cross-sectional Study

BACKGROUND Although dialysis patients are at high risk of stroke and have a high burden of cognitive impairment, there are few reports of anatomic brain findings in the hemodialysis population. Using magnetic resonance imaging of the brain, we compared the prevalence of brain abnormalities in hemodialysis patients with that in a control population without known kidney disease. STUDY DESIGN Cross-sectional cohort. SETTING & PARTICIPANTS 45 maintenance hemodialysis patients and 67 controls without reported kidney disease, both without history of known stroke. PREDICTOR The primary predictor was dialysis status. Covariates included demographics (age, race, and sex), vascular risk factors (diabetes and hypertension), and cardiovascular disease (coronary artery disease and congestive heart failure). OUTCOMES Magnetic resonance imaging of the brain features, including severity of white matter disease and cerebral atrophy (sulcal prominence and ventricular atrophy), hippocampal size, and small-/large-vessel infarcts. MEASUREMENTS Semiquantitative scale (0-9 for white matter disease and cerebral atrophy, 0-3 for hippocampal size) and infarct prevalence. RESULTS Mean ages of hemodialysis patients and controls were 55 ± 17 (SD) and 53 ± 13 years, respectively. In comparison to controls, hemodialysis patients had more severe white matter disease (1.6 vs 0.7) and cerebral atrophy (sulcal prominence, 2.3 vs 0.6; ventricular enlargement, 2.3 vs 0.9; hippocampal size, 1.3 vs 1.0), with all P < 0.001. In multivariable analyses, hemodialysis status was associated independently with worse white matter disease and atrophy grades. Hemodialysis patients also had a higher prevalence of small- (17.8%) and large- (7.8%) vessel infarcts than controls (combined, 22% vs 0%; P < 0.001). LIMITATIONS The dialysis cohort likely is healthier than the overall US hemodialysis population, partly limiting generalizability. CONCLUSIONS Hemodialysis patients have more white matter disease and cerebral atrophy compared with controls without known kidney disease. Hemodialysis patients also have a high prevalence of unrecognized infarcts.

Hypoglycemia and diffusion-weighted imaging

&NA; The effect of severe hypoglycemia on the brain is well known, ranging from alterations of mental status to profound coma and death. We describe a case of global diffusion abnormalities eventually resulting in death. This otherwise healthy patient presented with seizures and a serum glucose level less than 20 mg/dL. Testing suggested that the hypoglycemia was likely caused by exogenous insulin or perhaps insulin receptor antibodies. Magnetic resonance imaging on the day after admission showed regions of restricted diffusion in the temporal and occipital lobes as well as in the basal ganglia. Despite the large body of literature concerning the pathophysiology of hypoglycemia and its clinical implications, little is known regarding its radiologic correlations. Index Terms: hypoglycemia, diffusion, magnetic resonance imaging (MRI), seizure, metabolic disease

Magnetic Resonance Imaging of Intramedullary Spinal Cord Lesions: A Pictorial Review

Magnetic resonance imaging is the current imaging modality of choice in the evaluation of patients presenting with myelopathic symptoms in the search for spinal cord lesions. It is important for the radiologist to recognize and differentiate nonneoplastic from the neoplastic process of the spinal cord as the differentiation of the 2 entities is extremely crucial to the neurosurgeon. This article presents a broad spectrum of benign intramedullary spinal abnormalities including syrinx, contusion, abscess, infarction, myelitis, multiple sclerosis, sarcoid, cavernoma, and arteriovenous malformation. Rare intramedullary neoplasms including dermoid tumor, astrocytoma, ependymoma, hemangioblastoma, lymphoma, ganglioneuroblastoma, and metastases are also illustrated. The clinical presentation and magnetic resonance signal characteristics as well as the differential diagnosis of the intramedullary lesions are discussed. The potential pitfalls in the differentiation of tumors from nonneoplastic disease of the spinal cord are also elucidated.

Intracranial carotid artery calcification on head CT and its association with ischemic changes on brain MRI in patients presenting with stroke-like symptoms: retrospective analysis.

IntroductionOur purpose was to study the association between the intracranial arterial calcifications observed on head CT and brain infarcts demonstrated by MRI in patients presenting with acute stroke symptoms.MethodsInstitutional review board approval was obtained for this retrospective study which included 65 consecutive patients presenting acutely who had both head CT and MRI. Arterial calcifications of the vertebrobasilar system and the intracranial cavernous carotid arteries (intracranial carotid artery calcification, ICAC) were assigned a number (1 to 4) in the bone window images from CT scans. These four groups were then combined into high calcium (grades 3 and 4) and low calcium (grades 1 and 2) subgroups. Brain MRI was independently evaluated to identify acute and chronic large-vessel infarcts (LVI) and small-vessel infarcts (SVI). The relationship between ICAC and infarcts was evaluated before and after adjusting for demographics and cardiovascular risk factors.ResultsStatistical analysis could not be performed for the vertebrobasilar system due to an insufficient number of patients in the high calcium group. Of the 65 patients, 46 (71%) had a high ICAC grade on head CT. They were older and had a higher prevalence of cardiovascular risk factors. Acute SVI (P = 0.006), chronic SVI (P = 0.006) and acute LVI (P = 0.04) were associated with a high ICAC grade. After adjustment for age and other risk factors, only acute SVI was associated with a high ICAC grade (P = 0.002).ConclusionAlthough age emerged as the most important determinant of ischemic cerebral changes, there were rather complex interactions among multiple risk factors with different infarct types. A high ICAC grade demonstrated a correlation with acute SVI in our patients independent of these risk factors.