Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)

Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain.

Accurate and automated methods for measuring the thickness of human cerebral cortex could provide powerful tools for diagnosing and studying a variety of neurodegenerative and psychiatric disorders. Manual methods for estimating cortical thickness from neuroimaging data are labor intensive, requiring several days of effort by a trained anatomist. Furthermore, the highly folded nature of the cortex is problematic for manual techniques, frequently resulting in measurement errors in regions in which the cortical surface is not perpendicular to any of the cardinal axes. As a consequence, it has been impractical to obtain accurate thickness estimates for the entire cortex in individual subjects, or group statistics for patient or control populations. Here, we present an automated method for accurately measuring the thickness of the cerebral cortex across the entire brain and for generating cross-subject statistics in a coordinate system based on cortical anatomy. The intersubject standard deviation of the thickness measures is shown to be less than 0.5 mm, implying the ability to detect focal atrophy in small populations or even individual subjects. The reliability and accuracy of this new method are assessed by within-subject test-retest studies, as well as by comparison of cross-subject regional thickness measures with published values.

/pdf/measuring-the-thickness-of-the-human-cerebral-cortex-from-2nsexa0rmk.pdf

Measuring the thickness of the human cerebral cortex from magnetic resonance images

Parkinson's disease: Mechanisms and models

The field of aging and dementia is focusing on the characterization of the earliest stages of cognitive impairment. Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). Mild cognitive impairment refers to the clinical condition between normal aging and AD in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. When these persons are observed longitudinally, they progress to clinically probable AD at a considerably accelerated rate compared with healthy age-matched individuals. Consequently, this condition has been recognized as suitable for possible therapeutic intervention, and several multicenter international treatment trials are under way. Because this is a topic of intense interest, a group of experts on aging and MCI from around the world in the fields of neurology, psychiatry, geriatrics, neuropsychology, neuroimaging, neuropathology, clinical trials, and ethics was convened to summarize the current state of the field of MCI. Participants reviewed the world scientific literature on aging and MCI and summarized the various topics with respect to available evidence on MCI. Diagnostic criteria and clinical outcomes of these subjects are available in the literature. Mild cognitive impairment is believed to be a high-risk condition for the development of clinically probable AD. Heterogeneity in the use of the term was recognized, and subclassifications were suggested. While no treatments are recommended for MCI currently, clinical trials regarding potential therapies are under way. Recommendations concerning ethical issues in the diagnosis and the management of subjects with MCI were made.

https://homepage.univie.ac.at/peter.dal-bianco/memory-clinic/mcipetersen.pdf

Current concepts in mild cognitive impairment.

A micromethod adapted for automated determinations was used to measure basal plasma levels of homocyst(e)ine [H(e)]. These levels included the sum of free and bound forms of homocysteine, its disulfide oxidation product, homocystine, and the homocysteine-cysteine-mixed disulfide. Two groups of subjects were studied: apparently healthy individuals (n = 103) and patients with peripheral arterial occlusive disease (PAOD) (n = 47). Because age in PAOD patients was higher than in control subjects, the control subjects were subdivided into younger and older groups (aged 60 years or less and more than 60 years, respectively). The H(e) levels in the younger groups were 11.18 +/- 3.58 (mean +/- SD, expressed as homocysteine) and 8.58 +/- 2.82 nmol/ml in men and women, respectively; in the older groups, the levels were 10.74 +/- 2.16 and 9.04 +/- 2.16 nmol/ml in men and women, respectively. There was a positive correlation of H(e) levels with age in the younger control women (r = 0.373; p less than 0.02); no significant correlations were present in the other three control groups. Levels of H(e) in PAOD patients (15.44 +/- 5.76 and 17.04 +/- 8.26 nmol/ml in men and women, respectively) were significantly higher than those indicated above in the older controls. Next, the PAOD patients were assigned to two subgroups: 1) those with normal levels of H(e) (within two standard deviations of the mean of the control values) and 2) those with elevated levels of H(e). Age, cholesterolemia, and the prevalence of smoking and diabetes were similar in both subgroups. These results suggest that elevated plasma H(e) is an independent risk factor for arterial occlusive disease.

Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease.

Objective To determine initial locus and rate of degeneration of temporal lobe structures (total lobe, hippocampus and parahippocampus) in preclinical dementia. Background Postmortem studies suggest that the earliest changes in Alzheimer9s disease are neurofibrillary tangle formation in hippocampus and adjacent cortex. MRI volume analysis of temporal lobe structures over time in subjects prior to developing dementia may allow the identification of when these processes begin, the rate they develop, and which areas are key to symptom development. Methods 30 nondemented (NOD), healthy, elderly individuals enrolled in a prospective study of healthy aging evaluated annually over a mean of 42 months. Twelve subjects with subsequent cognitive decline were assigned to the preclinical dementia group (PreD). All 120 annual MRI studies analyzed by volumetric techniques assessed group differences in temporal lobe volumes and rates of brain loss. Results NOD as well as PreD subjects had significant, time-dependent decreases in hippocampal and parahippocampal volume. Rates of volume loss between the groups did not significantly differ. PreD cases had significantly smaller hippocampi when asymptomatic. Parahippocampal volume did not differ between PreD and NOD cases. Significant time-dependent temporal lobe atrophy was present only in PreD. Conclusions Hippocampal and parahippocampal atrophy occurs at a similar rate regardless of diagnostic group. Those who develop dementia may have smaller hippocampi to begin with, but become symptomatic because of accelerated loss of temporal lobe volume. Temporal lobe volume loss may mark the beginning of the disease process within six years prior to dementia onset.

Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia

Background Several studies have shown that individually memory, hippocampal volume, and motor measures presage the onset of dementia. It is unclear if these independently contribute to the prediction of mild cognitive impairment. Objective To determine the ability of memory, hippocampal volume, and a gait speed to independently predict cognitive decline in healthy elderly persons. Design A prospective, longitudinal, observational cohort study with a mean follow-up of 6 years. Participants One hundred eight optimally healthy elderly cognitively intact subjects. Main outcome measures Any cognitive impairment noted on the Clinical Dementia Rating Scale (score = 0.5) or persistent or progressive cognitive impairment. Cox modeling determined if time to onset of cognitive impairment was associated with baseline logical memory II test score (a measure of delayed recall), hippocampal volume (magnetic resonance imaging), or gait speed (time to walk 30 ft [9 m]) independent of age, sex, depression, or the allele producing the epsilon4 type of apolipoprotein E (APOE epsilon4). Results Questionable dementia occurred in 48 participants in a mean (SD) of 3.7 (2.4) years. This progressed to persistent cognitive impairment in 38 of these participants in a mean (SD) of 4.4 (2.4) years. Logical memory II test performance and hippocampal volume each predicted onset of questionable dementia, independent of age and sex. Time to walk 30 ft additionally contributed independently to the prediction of time to onset of persistent cognitive impairment. Possessing the APOE epsilon4 allele and depression did not enter either model significantly. Conclusions Models combining multiple risk factors should refine the prediction of questionable dementia and persistent cognitive impairment, harbingers of dementia. Individuals at risk for cognitive impairment may represent a high-risk group for intervention.

https://jamanetwork.com/journals/jamaneurology/articlepdf/781753/noc10212.pdf

Independent predictors of cognitive decline in healthy elderly persons

BACKGROUNDFor decades, the coronary heart disease (CHD) mortality rate has been four or more times higher in Finland than in France despite comparable intakes of dietary cholesterol and saturated fat. A potential answer to this paradox is provided by this study of 40 countries and the analyses of other nutrients in the diets besides cholesterol and saturated fat.METHODS AND RESULTSCHD death rates for men aged 55 to 64 years were derived from the World Health Organization annual vital statistics. Dietary intakes were gathered from the Food and Agriculture Organization of the United Nations database. Forty countries at various levels of economic development and 40 dietary variables were investigated, including a lipid score that combined the intakes of cholesterol and saturated fat (Cholesterol-Saturated Fat Index [CSI]). The CSI was significantly and positively related to CHD mortality in the 40 countries. The countries with low CSIs had low CHD death rates. Countries with high CSIs had a wide range of CHD...

Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox.

Objective: To assess whether changes in antemortem MRI brain volume measurements are valid predictors of subsequent Alzheimer disease (AD) pathology. Methods: Thirty-nine subjects, 15 nondemented and 24 with cognitive impairment, were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to cross-sectional and longitudinal volumetric measurements obtained from antemortem MRI. Results: Total brain volume change over time was related to the accumulation of cortical NFT. The rate of ventricular CSF volume increase was related to both cortical NFT and SP. The last hippocampal volume prior to death was related to hippocampal NFT burden; the rate of hippocampal volume atrophy was not related to hippocampal NFT pathology. These significant relationships continue to exist when all nondemented subjects are excluded from analysis. In subjects with cognitive impairment, the best predictor of cortical NFT and SP is the rate of ventricular volume increase. Excluding subjects with long duration between MRI and death did not appreciably alter results. Conclusions: MRI volumes measured over time are valid biomarkers of pathologic progression of AD across a range of antemortem clinical states. The rate of ventricular volume enlargement can be used to monitor disease progression or response to treatment in future clinical trials that are targeted at NFT and SP pathology.

Gary Sexton

Papers

Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease.

Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia

Independent predictors of cognitive decline in healthy elderly persons

Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox.

Changes in premorbid brain volume predict Alzheimer's disease pathology.