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C DeCarli

Publications and source records attributed to C DeCarli.

At least 19 recordsLinked to original sources
PubMed2000

Biobehavioral characteristics of nondemented older adults with subclinical brain atrophy.

OBJECTIVE: To characterize the risk factors and neuropsychological performance of two subgroups of community-dwelling, white elderly men free of severe cognitive impairment (n = 383; mean age, 72.9 +/- 3.0 years) who differ on volumetric measurements of total brain parenchyma and white matter hyperintensity (WMH) volumes. METHODS: Group comparisons were made of cerebrovascular disease risk factors measured at the time of imaging and at three prior examinations extending over 25 years of adult life. Measures of verbal memory and speed psychomotor processing at the time of imaging and 10 years before imaging were also available. RESULTS: Compared with those in the "nonatrophy" group, individuals in the subgroup with "atrophy" (defined by low total brain volume and high WMH volume) were older, reported a higher level of depressive symptomatology, experienced a steeper decline in diastolic blood pressure (DBP) and a steeper increase in pulse pressure, were less physically active, had smoked for more years, and had a higher prevalence of several cardiovascular disease indicators, including an ankle/arm systolic blood pressure ratio less than 0.9, and hypertension. After multivariate analysis, the 25-year decline in DBP, the number of years smoked, and an ankle/arm index of less than 0.9 remained significant discriminators of the two groups. Lower levels of speeded performance at the time of imaging and a steeper 10-year decline in cognitive performance on selected tests were also observed in the atrophic group. CONCLUSION: Community-dwelling older adults with volumetric brain measurements associated with accelerated aging are distinguishable on the basis of several health-related characteristics. These individuals also perform less well on certain tasks involving executive functioning.

Adult↗
PubMed2000

Head injury and the risk of AD in the MIRAGE study.

OBJECTIVES: It has been suggested in some studies that head injury is a risk factor for AD, and that this risk is heightened among carriers of the APOE-epsilon4 allele. We examined the effects of head injury and APOE genotype on AD risk in a large family study. SUBJECTS: A total of 2,233 probands who met criteria for probable or definite AD and their 14,668 first-degree family members (4,465 parents, 7,694 siblings, and 2,509 spouses) were ascertained at 13 centers in the United States, Canada, and Germany participating in the MIRAGE (Multi-Institutional Research in Alzheimer Genetic Epidemiology) project. Information on head injury was collected by interview of multiple informants and review of medical records. Nondemented relatives and spouses served as control subjects for this study. METHODS: Odds of AD for head trauma with or without loss of consciousness were computed by comparing probands with unaffected spouses using conditional logistic regression analysis. To account for the unique biologic relationship between probands and their parents and siblings, odds of AD were computed using a generalized estimating equation (GEE) Poisson regression approach. GEE logistic regression was used to examine the joint effects of APOE genotype and head injury on the odds of AD in probands and a control group comprised of unaffected siblings and spouses. RESULTS: Comparison of probands with their unaffected spouses yielded odds ratios for AD of 9.9 (95% CI, 6.5 to 15.1) for head injury with loss of consciousness and 3.1 (2.3 to 4.0) for head injury without loss of consciousness. The corresponding odds derived from the comparison of probands with their parents and sibs were 4.0 (2.9 to 5.5) for head injury with loss of consciousness and 2.0 (1.5 to 2.7) for head injury without loss of consciousness. Head injury without loss of consciousness did not significantly increase the risk of AD in spouses (OR = 1.3; 95% CI, 0.4 to 4.1). The joint effects of head injury and APOE genotype were evaluated in a subsample of 942 probands and 327 controls (spouses and siblings). Head injury increased the odds of AD to a greater extent among those lacking epsilon4 (OR = 3.3) than among epsilon4 heterozygotes (OR = 1.8) or homozygotes (OR = 1.3). CONCLUSION: Head injury is a risk factor for AD. The magnitude of the risk is proportional to severity and heightened among first-degree relatives of AD patients. The influence of head injury on the risk of AD appears to be greater among persons lacking APOE-epsilon4 compared with those having one or two epsilon4 alleles, suggesting that these risk factors may have a common biologic underpinning.

Aged↗
PubMed2000

Postoperative changes in cerebral metabolism in temporal lobe epilepsy.

BACKGROUND: Fludeoxyglucose F 18 positron emission tomography ((18)F-FDG-PET) can detect focal metabolic abnormalities ipsilateral to the seizure focus in 80% of patients with temporal lobe epilepsy (TLE). Regions outside the epileptogenic zone can also be affected. We hypothesized that these remote regions might show altered metabolism, tending to return toward normal values, after surgery. DESIGN: Interictal preoperative and postoperative (18)F-FDG-PET metabolism were compared in patients with refractory TLE. Based on pathological findings, disease was classified in the following 3 groups: mesial temporal sclerosis, mass lesions, and no pathological diagnosis. Quantitative PET data analysis was performed using the region-of-interest template previously described. Global normalization was used to adjust for the effect of antiepileptic medication changes. Data were analyzed by Wilcoxon signed rank test and analysis of variance. SETTING: The Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health. PATIENTS: Twenty-two patients with refractory TLE. RESULTS: Preoperatively, in all groups, cerebral metabolic rate for glucose was decreased ipsilateral to the resection site in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, in all groups, cerebral metabolic rate for glucose increased in ipsilateral inferior frontal area and thalamus. In the mesial temporal sclerosis group, we found a statistically significant increase in the contralateral thalamus. CONCLUSION: Temporal lobe epilepsy is associated with extensive preoperative decreased metabolism in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, we found increased IF and thalamic metabolism. Seizures may have a reversible effect on brain areas connected with, but remote from, the epileptogenic cortex. Arch Neurol. 2000;57:1447-1452

Adult↗
PubMed2000

The joint effect of apolipoprotein E epsilon4 and MRI findings on lower-extremity function and decline in cognitive function.

BACKGROUND: Cognitive decline and poor physical function are risk factors for disability in old age and may occur more often in subjects with the apolipoprotein E epsilon4 (ApoE-epsilon4) allele. The objective of this study was to investigate the joint effect of ApoE-epsilon4 and structural changes detected on MRI brain scans on cognitive decline and lower-extremity function. METHODS: Brain MRI (1.5 T), neuropsychological tests, and lower-extremity physical function tests were administered to World War II male veteran twins ages 69 to 80. Quantification of MRI scans used a previously published algorithm to segment brain images into total cerebral brain (TCB), cerebrospinal fluid (CSF), and white-matter hyperintensity (WMH) volumes. A short battery of physical performance tests was used to assess lower-extremity function. Ten-year changes in performance on the Mini-Mental State Exam (MMSE), the Benton Visual Retention Test (BVRT), and the Digit Symbol Substitution (DSS) test were used to assess cognitive decline. RESULTS: For the sample as a whole, the comparison of subjects by median split of total cerebral brain volume found that those with brain volumes below the median performed worse on tests of gait and balance (p < .01) and experienced greater cognitive decline on the MMSE and BVRT cognitive test batteries (both p < .01). In addition, subjects with WMH volumes above the median had poor performance on the standing balance tasks and experienced greater decline on the DSS test (p < .01). Stratified analyses revealed that the joint effect of radiological findings and the ApoE-epsilon4 allele on cognitive decline and lower-extremity function was often greater than that expected from the separate effects combined. CONCLUSIONS: We conclude that radiological findings in conjunction with ApoE-epsilon4 may single out a group at higher risk for dementia. We speculate that the observed interaction effect may be due to increased susceptibility to brain injury or impaired repair mechanisms in subjects with ApoE-epsilon4.

Aged↗
PubMed2000

Relationship of seizure frequency to hippocampus volume and metabolism in temporal lobe epilepsy.

PURPOSE: To examine the relationship between frequency of complex partial (CPS) and secondarily generalized tonic-clonic seizures (sGTCS) on hippocampal volume (HV) and temporal lobe metabolism. METHODS: We performed volumetric magnetic resonance imaging (MRI) and positron emission tomography with 18fluorodeoxyglucose (18FDG-PET) in 32 patients with epilepsy. Temporal lobe foci were localized by ictal video-EEG. RESULTS: We did not find any association between CPS frequency or lifetime number of sGTCS and HV or metabolism ipsilateral to electroencephalographic focus. CONCLUSION: The progress of metabolic or pathologic abnormalities of temporal lobe epilepsy may not be altered by adequate seizure control. The presence of an epileptic focus might be associated with progressive neuronal injury even in clinically well-controlled patients.

Adult↗
PubMed2000

Apolipoprotein E genotype and hippocampal asymmetry in Alzheimer's disease: a volumetric MRI study.

Asymmetry of brain structures is common to many species and is even present in utero. Some developmental, pathological, and dementing diseases are associated with alterations in normal anatomical asymmetries. Anatomical asymmetries, however, have been only superficially studied in Alzheimer's disease. Recent evidence indicates that the allele epsilon4 of the apolipoprotein E (ApoE), a well known risk factor for Alzheimer's disease, might play a part in determining some brain morphological changes both in normal carriers and in patients with Alzheimer's disease. This study evaluated the effect of the ApoE genotype on hippocampal asymmetry in patients with Alzheimer's disease carrying 0, 1, and 2 copies of the allele. Volumetric right-left differences of the hippocampi were computed in 28 right handed patients with Alzheimer's disease (14 -/-, 9 epsilon4/-, and 5 epsilon4/4) and 30 controls without detectable cognitive deficit. In controls, the right hippocampus was larger than the left, whereas in patients with Alzheimer's disease this asymmetry was progressively reduced with increasing gene dose of the epsilon4 allele, and the asymmetry was reversed in the epsilon4/4 Alzheimer's disease group. The mean right-left volume differences were: 1.2, 0.7, 0.2, and -1.0 in controls, -/-, epsilon4/-, and epsilon4/4 patients, respectively (sex adjusted p for trend=0.017). The data indicate a dose dependent effect of the ApoE epsilon4 allele on hippocampal volume asymmetry in Alzheimer's disease.

Aged↗
PubMed2000

Cerebrospinal fluid viral load is related to cortical atrophy and not to intracerebral calcifications in children with symptomatic HIV disease.

The relationships between viral load in plasma and cerebrospinal fluid (CSF) and computed tomography (CT) brain scan abnormalities were studied in 39 children between 0.5 and 13 years of age with symptomatic HIV-1 disease. Quantitative RNA PCR was used to determine HIV-1 RNA levels and a semiquantitative analog rating technique was used to evaluate non-contrast CT brain scans. CSF HIV-1 RNA copy number correlated significantly with CT brain scan ratings for severity of cortical atrophy (r = 0.36; P < 0.05) but not with ratings of intracerebral calcifications (r = -12; NS). The difference between these two correlations was significant (P < 0.05). Plasma HIV-1 RNA copy number did not correlate significantly with any CT brain scan ratings or with CSF viral load (r = 0.05; NS). Severity of cortical atrophy appeared to reflect the level of viral load in the CSF, supporting the notion that active HIV-1 replication in the CNS is at least in part responsible for such brain abnormalities in children. The lack of correlation of intracerebral calcifications with other CT brain scan abnormalities as well as with CSF viral load suggests that this lesion is relatively independent and may reflect a different neuropathologic process.

AIDS Dementia Complex↗
PubMed1999

APOE-epsilon4 is associated with less frontal and more medial temporal lobe atrophy in AD.

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 < 0.0005). In contrast, larger volumes were found in the frontal lobes with increasing e4 gene dose. When compared with controls, volume differences of the right frontal lobe were -11.8% in the -/- AD group, -8.5 in the e4/- group, and -1.4% in the e4/4 group (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.

Aged↗
PubMed1999

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

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.

Brain↗
PubMed1999

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

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.

Adult↗
PubMed1999

Differential genetic influence for components of memory in aging adult twins.

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<.001) but not for the other 3 components of memory. Using maximum likelihood methods, the best-fitting genetic model indicated that verbal learning and memory has a substantial genetic component (56% of total variance), whereas response discrimination has a much smaller, although still detectable, genetic component (24% of total variance). There is no evidence of genetic influence on learning strategy or recognition memory. 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.

Aged↗
PubMed1999

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

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 47.2+/-3.0 years at initial examination and 72. 5+/-2.9 years at final examination. Average blood pressure (BP) levels were normal, although 32% of the subjects had received or were currently taking antihypertensive medications. As a group, 31% had symptomatic cardiovascular disease, 11% had symptomatic cerebrovascular disease, and 8% had symptomatic peripheral vascular disease. Both systolic and diastolic BP levels at initial examination were inversely related to brain volume and positively related to WMHI volume. Multiple regression analysis identified BP-related measures and vascular risk factors as significant predictors of brain and WMHI volumes. In addition, the magnitude of orthostatic BP change was significantly associated with WMHI volume. Subjects with extensive amounts of WMHI had significantly higher systolic BP at the final examination and a higher prevalence of symptomatic cardiovascular and cerebrovascular disease, without significant differences in the prevalence of hypertension treatment. CONCLUSIONS: Midlife BP measures are significantly associated with later-life brain and WMHI volumes and the prevalence of symptomatic vascular disease. Since WMHI share cerebrovascular risk factors and extensive WMHI are associated with symptomatic vascular disease, extensive WMHI may be a subclinical expression of cerebrovascular disease. Careful treatment of midlife BP elevations may diminish these later-life brain changes.

Age Factors↗
PubMed1999

Impact of apolipoprotein E epsilon4 and vascular disease on brain morphology in men from the NHLBI twin study.

BACKGROUND AND PURPOSE: Apolipoprotein E epsilon4 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 brain volume, WMH, and the presence of stroke on MRI were obtained from the 396 participants in the final examination. The presence or absence of a history of coronary heart disease, cerebrovascular disease, peripheral arterial disease, and ApoE genotype were determined for each subject. RESULTS: Of the 396 men, 88 (22%) had at least 1 ApoE4 allele. ApoE4 was not associated with differences in age or education. While the prevalence of vascular disease was generally greater in the ApoE4 group, this was only significant for coronary heart disease (29.8% in subjects without ApoE4 versus 40.7% in subject with ApoE4; P=0.03). ApoE4 subjects had significantly smaller brain volumes (942.4+/-34.5 versus 952.2+/-40.1 cm(3); P=0. 02). MRI evidence of stroke was detected in 88 (22%) of the subjects. The distribution of ApoE genotype was marginally different between subjects with MRI-detected stroke compared with those without. Further analysis revealed that the co-occurrence of cerebrovascular disease and ApoE4 was associated with significantly greater brain atrophy and WMH than either ApoE4 or cerebrovascular disease alone. Similar relations were seen for coronary heart disease and peripheral arterial disease. CONCLUSIONS: We conclude that ApoE4 enhances the extent of brain abnormalities in the presence of various vascular diseases. We speculate that this effect may be mediated by an increased susceptibility to brain injury or impaired repair mechanisms associated with ApoE4.

Adult↗
PubMed1998

Extratemporal atrophy in patients with complex partial seizures of left temporal origin.

Total cerebral, temporal lobe, hippocampal, caudate, and lenticular nuclei volumes were quantified from magnetic resonance images of 21 patients with left temporal lobe epilepsy and medically intractable complex partial seizures. These regional brain volumes were compared with the same measures in 19 controls. No significant differences in total cerebral, left temporal lobe, right temporal lobe, or total temporal lobe volumes were found. As expected, left hippocampal volumes were significantly smaller in the patients with epilepsy than in control subjects. The left hippocampus-to-right hippocampus volume ratio was significantly lower in patients than in control subjects. In addition to left hippocampal volumes, mean left thalamic, left caudate, and bilateral lenticular volumes were significantly smaller in the patients with epilepsy than in control subjects. The left-to-right thalamic volume ratio was also significantly lower in the patients with epilepsy compared with control subjects, but there were no significant group differences in caudate or lenticular ratios. These results show that medically intractable temporal lobe epilepsy is associated with volume loss in brain structures outside the presumably involved hippocampus. The pathophysiological significance of our findings is uncertain. They could be related to the underlying cause of the disorder. However, volume loss also may reflect damage due to involvement of these structures in recurrent seizure activity.

Adult↗
PubMed1998

Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs), as detected by MRI, are common among the elderly and are frequently interpreted as representing a subclinical form of ischemic brain damage. We used volumetric MR techniques to investigate the contribution of genes and the environment to measures of brain morphology in a sample of community dwelling elderly male twins. METHODS: Brain MR (1.5 T) scans were obtained from 74 monozygotic (MZ) and 71 dizygotic (DZ), white, male, World War II veteran twins born in the United States and age 68 to 79 when scanned. MR quantification used a previously published semiautomated segmentation algorithm to segment brain images into total brain, cerebrospinal fluid (CSF), and WMH volumes. Twin pair covariances were computed for each measure, and structural equation genetic models were fitted to these data. RESULTS: Total cranial, brain parenchyma, CSF, and WMH volumes were highly correlated in MZ pairs, and correlations in MZ pairs were significantly greater than those in DZ pairs. Structural equation modeling indicated heritabilities of 91%, 92%, and 73%, respectively, for total cranial, brain parenchyma, and WMH volumes. Correction for age and head size reduced the heritability of brain parenchyma to 62% (95% confidence interval, 56% to 68%) and the heritability of WMH volume to 71% (95% confidence interval, 66% to 76%). Proband concordance rates for large amounts of WMH were 61% in MZ pairs and 38% in DZ pairs, compared with a prevalence of 15% in the entire sample. CONCLUSIONS: This study is the first to quantify the relative contribution of genetic and individual environmental influences to measures of brain morphology in the elderly.

Aged↗
PubMed1998

Association of midlife blood pressure to late-life cognitive decline and brain morphology.

OBJECTIVE: To investigate the association between midlife systolic blood pressure (SBP) and late-life cognitive decline and brain morphology in a sample of community-dwelling elderly men 68 to 79 years of age. METHODS: Subjects are surviving members from the prospective National Heart, Lung, and Blood Institute Twin Study (intake, 1969 to 1972) who, when examined for a fourth time in 1995 through 1997, underwent brain MRI and repeated assessment of neurobehavioral functioning. Quantification of the MR images determined cerebral volume and total volume of white matter hyperintensities (WMHIs) for 392 subjects. Midlife SBP levels measured in 1970, 1980, and 1985 were used to classify subjects into low, medium, and high midlife SBP categories. A 10-year change in performance on the Mini-Mental State Examination, Digit Symbol Substitution Test, Benton Visual Retention Test, and Verbal Fluency Test was also calculated for these subjects. For all reported analyses, patients were treated as genetically unrelated individuals. RESULTS: Subjects with high midlife SBP experienced a greater decline in cognitive performance and had larger WMHI volumes at follow-up in late life than did those with low midlife SBP. Decreased brain parenchyma and increased WMHI volumes were associated with decline in neurobehavioral functioning as measured in late life independent of age, education, and baseline levels of cognition. CONCLUSIONS: Midlife SBP is a significant predictor of both decline in cognitive function and MR volumetric measures of brain atrophy in late life. Because decline in neurobehavioral functioning was associated with decreased brain volume and increased WMHI volume, we conclude that the long-term impact of elevated SBP on decline in late-life neurobehavioral functioning is likely to be mediated through its chronic, negative effect on structural characteristics of the brain.

Adult↗
PubMed1998

Age-related vasodilatory response to acetazolamide challenge in healthy adults: a dynamic contrast-enhanced MR study.

PURPOSE: We examined age-related changes in baseline regional cerebral blood volume (rCBV) and response to acetazolamide stimulation by using dynamic contrast-enhanced MR imaging. METHODS: Thirty healthy volunteers ranging widely in age (23 to 82 years) were examined before and after intravenous injection of acetazolamide with dynamic susceptibility contrast-enhanced MR imaging. rCBV values were normalized for intersubject and intrasubject comparison by estimating an arterial input function directly from the imaging data. Preacetazolamide baseline rCBV and the percentage volume change index (PVCI) of the postacetazolamide to preacetazolamide state were calculated and examined as a function of age. RESULTS: Older adults (>50 years) had lower baseline rCBV per unit tissue than did younger adults (<50 years), but higher rCBV after acetazolamide stimulation. Baseline rCBV tended to decrease with age in the medial frontal and frontoparietal gray matter regions. Response to acetazolamide stimulation, measured by PVCI, showed a significant age-related increase in gray matter, approximately 0.5% per year. CONCLUSION: rCBV can be significantly increased after acetazolamide stimulation in the healthy aged. These results support the notion that age-related decreases in rCBV measured at rest reflect reduced regional metabolic requirements rather than reduced capacity for regional substrate delivery. These data serve as a normative baseline for comparison studies of rCBV vascular reserve in aging persons with various cerebrovascular disorders.

Acetazolamide↗