Marietta Scott

White matter lesions account for all age-related declines in speed but not in intelligence.

MRI scans measured white matter lesion prevalence (WMLP) in 65 people ages 65-84 years who also took 17 cognitive tests: 3 tests of general fluid intelligence, 3 of vocabulary, 2 of episodic and 3 of working memory, 2 of processing speed, and 4 of frontal and executive function. Entry of age with WMLP into regression equations as predictors of test scores showed that inferences about the functional relationships between markers of brain aging and cognitive impairments are seriously misleading if they are based on simple correlations alone. A new finding that WMLP accounts for all of the age-related variance between individuals in tests of speed and executive ability but for none of the age-related variance in intelligence revises current hypotheses that gross brain changes affect general fluid intelligence and other mental abilities solely through their effects on information-processing speed.

Vascular function in older adults with depressive disorder

BACKGROUNDnCerebrovascular disease plays an important role in depressive disorder, especially in older adults. An understanding of vascular function in depression is important etiologically and to develop innovative treatments that may improve prognosis by ameliorating vascular damage.nnnMETHODSnThis study assessed endothelial function, arterial stiffness, and atherosclerosis in a variety of vessel beds in 25 elderly subjects with depressive disorder compared with 21 nondepressed control subjects. Subjects underwent pulse wave velocity, pulse wave analysis, carotid intima media thickness analysis, and magnetic resonance imaging. A subset (16 patients and 15 control subjects) had assessment of biopsied small artery dilatation to acetylcholine to further assess endothelial function.nnnRESULTSnThe mean sample age was 72.4 years with an average age at onset for depression of 60 years. Mean carotid intima media thickness was significantly higher in depressed subjects (p < .01). Pulse wave velocity was 1.6 m/sec higher in depressed subjects (borderline significance). There was a significant reduction in the dilatation response to acetylcholine in preconstricted small arteries (p = .01). On magnetic resonance imaging, depressed subjects had significantly more dilated Virchow-Robin spaces in the basal ganglia (p = .01). Depressed subjects had greater volume of white matter lesions in all regions, but this did not reach statistical significance. There were no baseline differences in vascular risk.nnnCONCLUSIONSnDepression in the elderly is associated with poorer endothelial function and more atherosclerosis. This is associated with a greater white matter hyperintensities lesion load and basal ganglia microangiopathy. The use of vasoprotective drugs to improve endothelial function or retard atherosclerosis as depression-modifying agents should be explored.

Losses in gross brain volume and cerebral blood flow account for age-related differences in speed but not in fluid intelligence

Age-related gross head size; adjusted age-related change in brain volume and carotid and basilar blood flow; as well as scores on 3 tests of fluid intelligence (gf), 2 tests of information-processing speed, 2 memory tests, and 3 tests of executive function were obtained from 69 volunteers aged from 62 to 84 years. Brain volume negatively predicted scores on all 10 cognitive tasks, accounting for up to 78% of age-related variance in scores on the speed tasks and on 1 executive task. Cerebral blood flow (CBF) negatively predicted scores on 8 cognitive tasks, accounting for up to 36% of age-related variance in speed scores. However, neither brain volume nor CBF accounted for significant age-related variance between individuals on any of 3 gf tests. We conclude that speed, but not gf, is an exceptionally sensitive behavioral index of the progress of gross brain changes that affect cognition in old age and that speed and gf do not reflect integrity of the same functional systems.

Effects of global atrophy, white matter lesions, and cerebral blood flow on age-related changes in speed, memory, intelligence, vocabulary, and frontal function.

Brain images were obtained from 133 healthy people of ages 61-85 years who completed 20 tests of information processing speed, intelligence, frontal and executive function, memory, and vocabulary. Structural equation models examined relationships between cognitive test scores, ages and measurements of global age-associated atrophy, white matter lesions, and cerebral blood flow. These neurophysiological measures jointly account for all age-related variance in information processing speed. Speed entirely mediated relationships between neurophysiological measures and memory and partly mediated relationships between neurophysiological measures and intelligence and frontal function. Neurophysiological measures, but not calendar age, accounted for vocabulary scores. Cognitive slowing was responsible for some, but not all, age-related declines in mental function. Age-related declines in intelligence, frontal function, and speed were due to changes in different functional systems.

The Importance of Partial Voluming in Multi-dimensional Medical Image Segmentation

The presented method addresses the problem of multi-spectral image segmentation through use of a model which takes into account partial volumes of tissues being present in a single voxel at boundaries. The parameters of the multi-dimensional model of pure tissues and their mixtures are iteratively adjusted using an Expectation Maximisation (EM) optimisation technique. Bayes theory is used to generate probability maps for each segmented tissue which estimates the most likely tissue volume fraction within each voxel.

A fast, model-independent method for cerebral cortical thickness estimation using MRI

Several algorithms for measuring the cortical thickness in the human brain from MR image volumes have been described in the literature, the majority of which rely on fitting deformable models to the inner and outer cortical surfaces. However, the constraints applied during the model fitting process in order to enforce spherical topology and to fit the outer cortical surface in narrow sulci, where the cerebrospinal fluid (CSF) channel may be obscured by partial voluming, may introduce bias in some circumstances, and greatly increase the processor time required. In this paper we describe an alternative, voxel based technique that measures the cortical thickness using inversion recovery anatomical MR images. Grey matter, white matter and CSF are identified through segmentation, and edge detection is used to identify the boundaries between these tissues. The cortical thickness is then measured along the local 3D surface normal at every voxel on the inner cortical surface. The method was applied to 119 normal volunteers, and validated through extensive comparisons with published measurements of both cortical thickness and rate of thickness change with age. We conclude that the proposed technique is generally faster than deformable model-based alternatives, and free from the possibility of model bias, but suffers no reduction in accuracy. In particular, it will be applicable in data sets showing severe cortical atrophy, where thinning of the gyri leads to points of high curvature, and so the fitting of deformable models is problematic.

Age at onset and vascular pathology in late-life depression.

OBJECTIVEnThere is considerable evidence to suggest that late-onset depression may be etiologically distinct from early-onset depression. The aim of this study was to compare vascular function and magnetic resonance imaging-defined brain ischemic changes between early-onset depressed (EOD) and late-onset depressed (LOD) subjects.nnnDESIGNnCase-control study.nnnPARTICIPANTSnTwenty-five subjects with late-life depression recruited from secondary care were divided into groups with EOD (<60 years, 11 subjects) and LOD (>60 years, 14 subjects).nnnMEASURESnAll subjects underwent a variety of vascular assessments including pulse wave analysis, pulse wave velocity, carotid intima media thickness (IMT), and magnetic resonance imaging of the brain to assess white matter hyperintensities.nnnRESULTSnThe mean age of LOD subjects was 71.3 ± 4.0 years and EOD was 73.6 ± 4.7 years (p = NS). There were no baseline differences in vascular risk or sociodemographic variables. LOD subjects had significantly higher common carotid IMT (EOD: 0.06 [0.01]; LOD: 0.09 [0.02], p = 0.02), carotid plaques (EOD: 2.1 [1.1]; LOD: 5.4 [3.9], p = 0.02), and peripheral augmentation index (EOD: 81.7 [7.9]; LOD: 96.2 [21.6], p = 0.04) when compared with early-onset subjects, indicating more vascular pathology. There were no group differences in white matter hyperintensities. Age at onset of depression was positively correlated with peripheral augmentation index, common carotid IMT, and plaque index.nnnCONCLUSIONnThis study suggests that elderly subjects with LOD have greater vascular impairment than those with an early-onset illness. Whether preventing vascular disease at an earlier age may decrease the risk of last onset depression is a potential area for future research.

Potential surrogate markers of cerebral microvascular angiopathy in asymptomatic subjects at risk of stroke

Cerebral microvascular angiopathy (MVA) is associated with clinical vascular risk factors and is characterised by histological changes, including thickening of the walls of arterial vessels and dilatation of the Virchow-Robin spaces (VRS). We have previously described two novel biomarkers of MVA based on magnetic resonance imaging (MRI), VRS dilatation and abnormalities in the transfer of systolic arterial pulsation to the ventricular CSF, which occur as a result of decreased cerebral arterial compliance. These are associated with vascular dementia and treatment-resistant late onset depression. We studied a group of normal subjects at risk of cerebrovascular disease to determine if these biomarkers are present in patients who have no evidence of symptomatic vascular disease. We studied 31 subjects, 16 with three or more vascular risk factors and 15 with one or less significant risk factors. We measured arterial blood flow and CSF flow in the cerebral aqueduct, white matter lesion load, and the distribution and number of VRS. There were significant differences in CSF pulsatility and in VRS in the basal ganglia between the two groups, but no differences in white matter lesion load. We conclude that asymptomatic subjects at risk of stroke have MRI evidence of MVA before white matter lesions become apparent.

Bayesian and non-Bayesian probabilistic models for medical image analysis

Abstract Bayesian approaches to data analysis are popular in machine vision, and yet the main advantage of Bayes theory, the ability to incorporate prior knowledge in the form of the prior probabilities, may lead to problems in some quantitative tasks. In this paper we demonstrate examples of Bayesian and non-Bayesian techniques from the area of magnetic resonance image (MRI) analysis. Issues raised by these examples are used to illustrate difficulties in Bayesian methods and to motivate an approach based on frequentist methods. We believe this approach to be more suited to quantitative data analysis, and provide a general theory for the use of these methods in learning (Bayes risk) systems and for data fusion. Proofs are given for the more novel aspects of the theory. We conclude with a discussion of the strengths and weaknesses, and the fundamental suitability, of Bayesian and non-Bayesian approaches for MRI analysis in particular, and for machine vision systems in general.

Age-associated losses of brain volume predict longitudinal cognitive declines over 8 to 20 years.

Absolute differences in global brain volume predict differences in cognitive ability among healthy older adults. However, absolute differences confound lifelong differences in brain size with amounts of age-related shrinkage. Measurements of cerebrospinal fluid (CSF) volume were made to estimate age-related shrinkage in 93 healthy volunteers aged 63 to 86 years. Their current levels of brain shrinkage predicted their amounts of decline over the previous 8 to 20 years on repeated assessments during a longitudinal study on the Cattell Culture Fair Intelligence Test, on two tests of information processing speed, and marginally on the Wechsler Adult Intelligence Scale (D. Wechsler, 1981), but not on three memory tests. Loss of brain volume is an effective marker both for current cognitive status and for amounts and rates of previous age-related cognitive losses.