Showing papers by "Charles DeCarli published in 2003"

Mild cognitive impairment: prevalence, prognosis, aetiology, and treatment.

Abstract: Summary Mild cognitive impairment (MCI) is a recently described syndrome that is currently thought of as a transition phase between healthy cognitive ageing and dementia. Although this notion seems to be reasonable, the general nature of the term MCI—including its many definitions—makes accurate accounting of the prevalence, prognosis, and potential benefit from treatment somewhat difficult. The differences in cognitive profile and clinical progression among individuals with MCI are generally recognised. However, recent evidence also suggests that the aetiological heterogeneity among individuals with MCI could be greater than previously reported. For example, cerebrovascular disease seems to be underestimated as a potential cause of MCI. In this review, I attempt to recognise workable definitions of MCI to discuss the prevalence, pathophysiology, prognosis, and possibilities for treatment of this disorder.

Cerebrospinal Fluid Tau and β-Amyloid: How Well Do These Biomarkers Reflect Autopsy-Confirmed Dementia Diagnoses?

Abstract: Background Tau and β-amyloid (Aβ) are proposed diagnostic biomarkers for Alzheimer disease (AD). Previous studies report their relationship to clinical diagnoses of AD and other dementias. To understand their value as predictors of disease-specific patholody, levels determined during life must be correlated with definitive diagnoses in mixed dementia groups and cognitively normal subjects. Objectives To correlate antemortem cerebrospinal fluid (CSF) tau and Aβ levels with definitive dementia diagnosis in a diverse group of patients; to calculate statistics for CSF tau and Aβ. Design Prospective study. Setting Ten clinics experienced in the diagnosis of neurodegenerative dementias. Patients One hundred six patients with dementia and 4 cognitively normal subjects with a definitive diagnosis, and 69 clinically diagnosed cognitively normal subjects. Main Outcome Measures Correlation of CSF tau and Aβ with final diagnosis. Results Mean tau level was 612 pg/mL for the 74 patients with AD, 272 pg/mL for 10 patients with frontal dementia, 282 pg/mL for 3 patients with dementia with Lewy bodies, and 140 pg/mL for 73 cognitively normal control subjects. Tau was less than 334 pg/mL for 20 patients with AD. Aβ 42 was reduced in patients with AD (61 fmol/mL) compared with patients with frontal dementia (133 fmol/mL) and control subjects (109 fmol/mL), but not compared with patients with dementia with Lewy bodies (14 fmol/mL) or prion disease (60 fmol/mL). Conclusions Elevated CSF tau levels are associated with AD pathology and can help discriminate AD from other dementing disorders. However, some patients with AD have a level less than the mean ± 2 SDs of the cognitively normal cohort.

A Pilot Study of Vitamins to Lower Plasma Homocysteine Levels in Alzheimer Disease

Abstract: OBJECTIVE Authors determined the impact of high-dose vitamin supplements on plasma homocysteine levels in patients with Alzheimer disease (AD). METHODS Authors used an open-label trial of folic acid, vitamin B 12 , and vitamin B 6 , in combination for 8 weeks, with measurement of plasma homocysteine levels in the fasting state and after methionine-loading. A total of 69 subjects with AD were enrolled, including 33 who were taking standard multivitamin supplements; 66 were available at 8-week follow-up. RESULTS The high-dose vitamin regimen was associated with a significant reduction in fasting and post–methionine-loading homocysteine. Reductions were greater in the subgroup not using multivitamins, but were also significant in the multivitamin users. CONCLUSION High-dose vitamin supplementation reduces homocysteine levels in patients with AD. The effect of supplementation on rate of cognitive decline will be assessed later in a randomized, double-blind study.

Hippocampal volume is associated with memory but not nonmemory cognitive performance in patients with mild cognitive impairment

Abstract: Mild cognitive impairment (MCI) appears to be a transitional stage in the development of Alzheimer's disease (AD). Patients with MCI show impaired memory performance and hippocampal atrophy relative to normal elderly controls. Prior studies indicate that the degree of hippocampal atrophy in MCI patients predicts conversion to AD. In contrast to patients with MCI who have deficits primarily in memory, AD patients have clinically evident impairments in both memory and nonmemory cognitive domains. One explanation for the observation that a smaller hippocampal volume predicts conversion to AD might be that hippocampal atrophy is associated with early impairment in nonmemory cognitive areas as well as memory. A link between hippocampal volume and nonmemory function could occur if hippocampal atrophy was correlated with AD pathology in other brain regions. We therefore sought to determine the relationship of hippocampal volume with performance on memory and nonmemory tasks in patients with MCI. Although we found a significant correlation between hippocampal volume and memory performance, we did not find a significant correlation between hippocampal volume and nonmemory performance. We conclude that the relationship between hippocampal volume and risk of AD is likely tied to reduced memory performance and not associated with impairment in nonmemory cognitive domains.

The role of cerebrovascular disease in dementia.

Abstract: BACKGROUND–Improvements in health care over the last 50 years have lengthened average life expectancy significantly, resulting in considerable growth of the population over 65 years of age. With increased age, however, comes an increased risk for Alzheimer’s disease (AD), and the prevalence of AD is

Total Cerebral Volume Is Reduced in Patients With Localization-Related Epilepsy and a History of Complex Febrile Seizures

Abstract: Context Febrile seizures may lead to later epilepsy. They have been associated with hippocampal atrophy but their effect on total cerebral volume is unknown. Objective To compare total cerebral volume in patients with mesial temporal lobe epilepsy with and without a history of complex febrile seizures (CFS). Design Survey. Setting Epilepsy monitoring center. Subjects Forty patients with localization-related epilepsy and temporal lobe onset determined by video electroencephalogram and 20 controls. Intervention Magnetic resonance imaging measurement of cerebral volume. Main Outcome Measure Total cerebral volume. Results Patients with a history of CFS had significantly reduced total cerebral volume compared with patients without CFS. In addition, male patients with CFS had significantly lower total cerebral volume than male normal controls. There was no significant difference between patients without CFS, or all patients, and controls. Conclusion Complex febrile seizures may have a global effect on brain development.

Prevention of white-matter lesions through control of cerebrovascular risk factors.

Abstract: Multiple epidemiological and brain imaging studies show a strong association between elevations in systolic blood pressure and lesions of cerebral white matter. The association between white-matter lesions and systolic blood pressure persists even if individuals are receiving treatment, suggesting that these individuals may be undertreated. In addition, these studies suggest that lesions of cerebral white matter may serve as markers for atherosclerotic vascular disease. Treatment strategies, therefore, should focus on early and aggressive management of elevated blood pressure, but definitions of elevated blood pressure may need to be revised downward to achieve best results.

White matter changes, creatinine, age, and ankle-arm index predicted incident MRI-defined infarctions in older adults.

Abstract: Source Citation Longstreth WT Jr, Dulberg C, Manolio TA, et al. Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: the ...