Showing papers by "Charles DeCarli published in 1999"

Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with partial seizures.

Abstract: Background: Previous studies have suggested a variety of factors that may be associated with the presence of hippocampal formation (HF) atrophy in patients with complex partial seizures (CPS), including a history of complex or prolonged febrile seizures (FS), age at seizure onset, and epilepsy duration. Objective: To determine whether epilepsy duration is related to HF atrophy. Methods: We performed MRIs on 35 patients with uncontrolled CPS who had temporal lobe ictal onset on video-EEG. None had evidence for an alien tissue lesion or extra-hippocampal seizure onset. All had a history of secondary generalization. Brain structures were drawn on consecutive images and pixel points summed from successive pictures to calculate volumes. Results: Nine patients with a history of complex or prolonged FS had smaller ipsilateral HF volume and ipsilateral/contralateral ratio than did patients without a history of FS. Epilepsy duration had a significant relation to ipsilateral HF volume and ipsilateral/contralateral ratio. In a multivariate analysis, the effect of duration, but not age at onset or scan, was significant. Patients with a history of FS did not have earlier age at epilepsy onset or longer duration. Conclusions: A history of FS predicted the severity of HF atrophy in our patients. Age at onset or study was not a significant factor. Epilepsy duration, however, did have a significant effect, suggesting that, after an initial insult, progressive HF damage may occur in patients with persistent seizures.

Predictors of brain morphology for the men of the NHLBI twin study

Abstract: Background and Purpose—Cross-sectional studies show that cerebrovascular risk factors are associated with increased brain atrophy, accumulation of abnormal cerebral white matter signals, and clinically silent stroke We extend these findings by examining the relationship between midlife cerebrovascular risk factors and later-life differences in brain atrophy, amount of abnormal white matter, and stroke on MRI Methods—Subjects were the 414 surviving members of the prospective National Heart, Lung, and Blood Institute Twin Study, who have been examined on 4 separate occasions, spanning the 25 years between 1969–1973 and 1995–1997 Quantitative measures of brain volume, volume of abnormal white matter signal (WMHI), and volume of stroke, when present, were obtained from those participating in the fourth examination Results—The mean±SD age of the subjects was 472±30 years at initial examination and 725±29 years at final examination Average blood pressure (BP) levels were normal, although 32% of the sub

APOE-ε4 is associated with less frontal and more medial temporal lobe atrophy in AD

Abstract: Objective: To test the hypothesis that the e4 allele of APOE is associated with a region-specific pattern of brain atrophy in AD. Methods: Volumes of the hippocampi, entorhinal cortices, and anterior temporal and frontal lobes were measured in 28 mild to moderate AD patients and 30 controls using MRI. Within the AD group, 14 patients were noncarriers (−/−), 9 were heterozygous (e4/−), and 5 were homozygous (e4/4) for the e4 allele. Dementia severity was similar across the three AD groups. Results: Smaller volumes were found with increasing dose of the e4 allele in the hippocampus, entorhinal cortex, and anterior temporal lobes in AD patients. When compared with controls, the volume loss in the right and left temporal regions ranged from −15.3 to −22.7% in the −/− AD group, from −26.2 to −36.0% in the e4/− group, and from −24.0 to −48.0% in the e4/4 group ( p p = 0.03). Conclusions: We found smaller volumes in the temporal lobe regions but larger volumes in the frontal lobes with increasing APOE -e4 gene dose in AD patients. These data suggest a region-specific biological effect of the e4 allele in the brains of AD patients.

Midlife cardiovascular risk factors and brain morphology in identical older male twins.

Abstract: Objective: Structural changes in the human brain have been reported to a greater extent in subjects with cardiovascular risk factors. We conducted a matched co-twin analysis of elderly monozygotic twins from the National Heart, Lung, and Blood Institute Twin Study to examine the association between midlife cardiovascular risk factors and MRI-based measures of brain atrophy. Methods: Brain MRIs (1.5-T) were obtained from 74 monozygotic, white, male, World War II veteran twins born in the United States from 1917 to 1927 and age 68 to 79 at the time of the brain scan. A semiautomated algorithm was used to segment brain images into total brain, CSF, and white matter hyperintensity volumes. Cardiovascular risk factors, medical history variables, and health practices were available from data collected over 25 years of adult life. Results: Independent of shared genetic or familial influences, within-pair differences in midlife glucose levels, high-density lipoprotein cholesterol, and systolic blood pressure were significantly associated with differences in white matter hyperintensities. Within-pair differences in coronary heart disease history and in current consumption of alcohol and level of physical activity were significantly associated with differences in brain parenchyma. In addition, within-pair differences in white matter hyperintensity volumes were significantly associated with differences in performance on cognitive and physical function tests and self-reports of depression symptoms. Conclusion: Independent of age effects and shared genetic or familial influences, midlife cardiovascular risk factors and lifetime health practices were predictive of structural brain changes in old age.

Impact of Apolipoprotein E ε4 and Vascular Disease on Brain Morphology in Men From the NHLBI Twin Study

Abstract: Background and Purpose—Apolipoprotein E e4 genotype (ApoE4) has been associated with increased risk for cardiovascular disease morbidity or mortality. This appears to be mediated by an ApoE4-related increase in cardiovascular atherosclerosis. Given the similarities between risk factors for heart disease and risk factors for stroke, a positive association between ApoE4 and stroke would be expected. Since age-related brain atrophy and the extent of white matter hyperintensities (WMH) share similar risk factors, we examined the combined effect of ApoE4 and history of vascular disease on brain volume, WMH, and MRI evidence of stroke. Methods—Subjects were the surviving members of the National Heart, Lung, and Blood Institute Twin Study. This is a longitudinal study of the effects of cardiovascular disease risk factors in community-dwelling male veterans. The fourth and final examination of this cohort included cerebral MRI and was completed in 1997. Apolipoprotein E (ApoE) genotype, quantitative measures of b...

Differential Genetic Influence for Components of Memory in Aging Adult Twins

Abstract: Objective To investigate the relative proportion of genetic and environmental contributions to verbal memory in community-dwelling World War II veteran twins. Design The California Verbal Learning Test (CVLT) was administered to 94 monozygotic (MZ) and 89 dizygotic (DZ) elderly male twin pair participants in the fourth examination of the National Heart, Lung, and Blood Institute Twin Study. Setting Subjects voluntarily participated on an outpatient basis at a research or medical center facility in 1 of 4 sites in the United States. Participants Subjects had a mean age of 71.8 years (SD, 2.9 years), a mean educational level of 13.6 years (SD, 2.8 years), and no history of stroke and/or a Mini-Mental State Examination score of 23 or greater. Main Outcome Measures Twin pair similarity in performance on 4 factor analytically derived components of the CVLT measuring verbal learning and memory, response discrimination, learning strategy, and recognition memory. Results The MZ intraclass correlation was significantly larger than the DZ correlation for verbal learning and memory (I Conclusion Differential contribution of genetic and environmental influences to specific components of memory suggest that, in this group of elderly male twin pairs, some components may be more amenable to intervention than others.

Imaging of static brain lesions in vascular dementia: implications for clinical trials.

Abstract: Vascular dementia (VaD) relates to different vascular mechanisms and changes in the brain and has different causes and clinical manifestations, reflecting complex interactions between vascular etiologies, changes in the brain, host factors, and cognition. Critical elements to the concept and diagnosis of VaD are defining the vascular causes, the vascular etiologies, and changes in the brain. Verifying the relation between brain lesions and cognition (i.e., the extent to which brain changes cause, compound, or coexist with cognitive impairment) and establishing the types, extent, side, site, and tempo of brain lesions that relate to incident cognitive impairment are major diagnostic challenges. Previous work on interactions between brain lesion and cognition in to cerebrovascular disease (CVD) have shown variation in the definitions and measures of cognitive impairment, in the techniques and methods used to reveal different brain changes, and in the selection of patient populations. Furthermore, small sample sizes and the absence of multivariate statistics have been design limitations. Accordingly, the different sets of criteria used and methods applied identify different numbers and clusters of subjects and different distribution of brain changes. Furthermore, this heterogeneity is reflected in variation in natural history such as the rate of progression of decline in different cognitive domains over time. All these factors have hampered optimal designs of clinical drug trials. A summary of generalizations regarding lesion and cognition interaction in VaD can be made. (1) Not a single feature, but a combination of infarct features--extent and type of white matter lesions (WMLs), degree and site of atrophy, and host factor characteristics--constitues correlates of VaD. (2) Infarct features favoring VaD include bilaterality, multiplicity (>1), location in the dominant hemisphere, and location in the limbic structures (fronto- and mediolimbic). (3) WML features favoring VaD are extensive WMLs (extensive periventricular WMLs and confluent to extensive WMLs in the deep WM). (4) It is doubtful that only a single small lesion could provide imaging evidence for a diagnosis of VaD. (5) Absence of CVD lesions on computed tomography or magnetic resonance imaging is strong evidence against a diagnosis of VaD. In forthcoming protocols on CVD-associated cognitive impairment, the following brain imaging features should be specified: detailed characterization of brain changes; use of possible predefined subtypes based on brain imaging; use of rating of vascular burden; defining the type and extent of WMLs favoring a diagnosis of VaD; defining the extent of medial temporal lobe atrophy disfavoring a diagnosis of VaD; and technical harmonization of methods of scanning and analysis.