White matter hyperintensities as a predictor of ne
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神经科学杂志 2005年第9期
1 Department of Psychology, University of Helsinki and Unit of Neuropsychology, Department of Neurology, Helsinki University Central Hospital, Finland
2 Department of Psychology, University of Helsinki, Finland
3 Department of Radiology, Helsinki University Central Hospital, Finland
4 Unit of Neuropsychology, Department of Neurology, Helsinki University Central Hospital, Finland
5 Department of Neurology, Lohja Hospital and Memory Research Unit, Department of Neurology, Helsinki University Central Hospital, Finland
6 Department of Neurology, Helsinki University Central Hospital, Finland
7 Memory Research Unit, Department of Neurology, Helsinki University Central Hospital, Finland
ABSTRACT
Objectives: Cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are a recognised risk factor for post-stroke dementia. Their specific relations to cognitive impairment are still not well known. The purpose of this study was to explore how the severity and location of WMHs predict neuropsychological test performance in the context of other brain lesions in elderly stroke patients.
Methods: In the Helsinki Stroke Aging Memory Study, 323 patients, aged from 55 to 85 years, completed a detailed neuropsychological test battery and MRI 3 months after an ischaemic stroke. The demographic and MRI predictors of cognition were studied with sequential linear regression analyses.
Results: After age, education and total infarct volume were controlled for, the overall degree of WMHs predicted poor performance in tests of mental speed, executive functions, memory, and visuospatial functions, but not in those of short term memory storage or verbal conceptualisation. However, the contribution of separate white matter regions was relatively low. Only the lesions along the bodies of lateral ventricles were independently associated with speed and executive measures. Additionally, general cortical atrophy clearly predicted a wide range of cognitive deficits while infarct volume had less relevance. Further analyses revealed that executive functions act as a strong mediator between the relationship of WMHs to memory and visuospatial functions.
Conclusions: The degree of WMHs is independently related to post-stroke cognitive decline. The most affected cognitive domains seem to be executive functions and speed of mental processing, which may lead to secondary deficits of memory and visuospatial functions.
Abbreviations: FOME, Fuld Object Memory Evaluation; MRI, magnetic resonance imaging; PVH, periventricular hyperintensity; PVH-B, white matter hyperintensities along the bodies of lateral ventricles; PVH-FH, white matter hyperintensities around frontal horns; PVH-OH, white matter hyperintensities around occipital horns; WAIS-R, Wechsler Adult Intelligence Scale-Revised; WCST, Modified Wisconsin Card Sorting Test; WMH, white matter hyperintensity; WMH-D, white matter hyperintensities in deep, watershed and subcortical white matter areas; WMS, Wechsler Memory Scale; WMS-R, Wechsler Memory Scale-Revised
Keywords: cognition; cortical atrophy; executive functions; stroke; white matter hyperintensities
Cerebral white matter hyperintensities (WMHs) are a common finding on magnetic resonance imaging (MRI) in patients with cerebrovascular diseases and also in healthy elderly persons. Their frequency is correlated with increasing age, vascular risk factors,1,2 cognitive impairment,2,3 and dementia.4 Several studies with neurologically healthy individuals have shown that WMHs, especially around the periventricular area, are related to deficits in speed of cognitive processing and attention.5–7 It has been suggested that executive functions mediated by the frontal lobe are particularly vulnerable to the effects of WMHs.8,9 The underlying cause for the observed relationship is assumed to lie in a disruption of the frontal subcortical circuits, which compromises the integrity of the frontal lobe functions.10–12 Nevertheless, the clinical relevance of the location of WMHs is still not well known.
Along with the population based studies, much of the literature on white matter has centred on memory clinic samples and dementia outpatients. A central feature of vascular cognitive impairment and dementia with subcortical small vessel pathology seems to be an impairment of executive functioning.13,14 Previous studies have also indicated that WMHs are an important risk factor for post-stroke dementia,15 together with complex interactions of infarct features and brain atrophy.16 Despite the fact that WMHs are commonly found in stroke patients, studies investigating their specific role in cognitive performance in this population are few. Recently, Burton and co-workers17 suggested that in older stroke patients the volume of WMHs, particularly in the frontal regions, is related to diminished cognitive processing speed and attention, while the volume of temporal lobe hyperintensities is associated with memory impairment. In addition, Sachdev and colleagues18 have reported a correlation between white matter pathology and cognitive dysfunction in patients with stroke or transient ischaemic attack.
The purpose of this study was to explore how the severity and location of WMHs predict performance in neuropsychological tests in elderly stroke patients. In our large stroke cohort, we earlier demonstrated that WMHs are associated with executive dysfunction.19 In this study, we aimed to investigate in further detail the role of WMHs in executive deficits and mental slowing, and the mediating effects of these deficits to other cognitive functions. Periventricular hyperintensities (PVHs) were analysed separately around both frontal (PVH-FH) and occipital horns (PVH-OH), and along the bodies of the lateral ventricles (PVH-B). In addition, the non-periventricular WMHs in deep, watershed, and subcortical areas (WMH-D) were examined. Total infarct volume, general cortical atrophy, and host factors were considered to be covariate predictors of cognition.
METHODS
Patients and study design
The Helsinki Stroke Aging Memory Study is a prospective cross sectional study of elderly patients with ischaemic stroke. The patients were 55 to 85 years of age and they were recruited consecutively at the emergency unit of the Helsinki University Central Hospital, Helsinki, Finland (n = 486). The details of the protocol and cohort have been reported previously.20 The patients went through a clinical assessment, brain MRI, and a comprehensive neuropsychological examination 3 months after the index stroke. In this study, we included patients who succeeded in completing both the neuropsychological test battery and MRI adequately (n = 323). The ethics committee of the Department of Neurology, Helsinki University Central Hospital, approved the study, and all patients participating in the study gave an informed consent.
Neuropsychological examination
The neuropsychological examination was conducted by observers blinded to the neuroradiological data. The test methods are clinically widely established and they were presented according to their standard instructions and scoring. The details have been described in previous reports.21,22
Mental speed
Speed of mental processing and attention were assessed with the Trail Making test part A,23 and a modified short form of the Stroop test (24 items with four colours), the coloured dots section (Stroop dots).24,25 In both of these tests, the time taken to complete the task was recorded. No corrections were made for errors.
Executive functions
The Trail Making test part B,23 and the short form of the Stroop test, coloured colour names section (Stroop words),24,25 were used in evaluating mental flexibility, set shifting, and response inhibition. In both conditions, the time taken to complete the test and the correct responses were recorded. Errors were not corrected. A modified version of the Wisconsin Card Sorting test (WCST)26 was used in assessing abstract problem solving and the ability to shift cognitive sets. The total number of correct responses and perseverative errors were recorded. Verbal fluency was measured in letter generation (letter K) and semantic category (animals), both in 60 seconds,25 and were considered in conjunction with the other executive tests.
Memory functions
Digit span forward and backward tasks were administered according to the Wechsler Memory Scale (WMS)27 in measuring short term storage and working memory. The tasks were included in the final analysis as a sum variable, as they gave identical results. Verbal memory was assessed b
2 Department of Psychology, University of Helsinki, Finland
3 Department of Radiology, Helsinki University Central Hospital, Finland
4 Unit of Neuropsychology, Department of Neurology, Helsinki University Central Hospital, Finland
5 Department of Neurology, Lohja Hospital and Memory Research Unit, Department of Neurology, Helsinki University Central Hospital, Finland
6 Department of Neurology, Helsinki University Central Hospital, Finland
7 Memory Research Unit, Department of Neurology, Helsinki University Central Hospital, Finland
ABSTRACT
Objectives: Cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are a recognised risk factor for post-stroke dementia. Their specific relations to cognitive impairment are still not well known. The purpose of this study was to explore how the severity and location of WMHs predict neuropsychological test performance in the context of other brain lesions in elderly stroke patients.
Methods: In the Helsinki Stroke Aging Memory Study, 323 patients, aged from 55 to 85 years, completed a detailed neuropsychological test battery and MRI 3 months after an ischaemic stroke. The demographic and MRI predictors of cognition were studied with sequential linear regression analyses.
Results: After age, education and total infarct volume were controlled for, the overall degree of WMHs predicted poor performance in tests of mental speed, executive functions, memory, and visuospatial functions, but not in those of short term memory storage or verbal conceptualisation. However, the contribution of separate white matter regions was relatively low. Only the lesions along the bodies of lateral ventricles were independently associated with speed and executive measures. Additionally, general cortical atrophy clearly predicted a wide range of cognitive deficits while infarct volume had less relevance. Further analyses revealed that executive functions act as a strong mediator between the relationship of WMHs to memory and visuospatial functions.
Conclusions: The degree of WMHs is independently related to post-stroke cognitive decline. The most affected cognitive domains seem to be executive functions and speed of mental processing, which may lead to secondary deficits of memory and visuospatial functions.
Abbreviations: FOME, Fuld Object Memory Evaluation; MRI, magnetic resonance imaging; PVH, periventricular hyperintensity; PVH-B, white matter hyperintensities along the bodies of lateral ventricles; PVH-FH, white matter hyperintensities around frontal horns; PVH-OH, white matter hyperintensities around occipital horns; WAIS-R, Wechsler Adult Intelligence Scale-Revised; WCST, Modified Wisconsin Card Sorting Test; WMH, white matter hyperintensity; WMH-D, white matter hyperintensities in deep, watershed and subcortical white matter areas; WMS, Wechsler Memory Scale; WMS-R, Wechsler Memory Scale-Revised
Keywords: cognition; cortical atrophy; executive functions; stroke; white matter hyperintensities
Cerebral white matter hyperintensities (WMHs) are a common finding on magnetic resonance imaging (MRI) in patients with cerebrovascular diseases and also in healthy elderly persons. Their frequency is correlated with increasing age, vascular risk factors,1,2 cognitive impairment,2,3 and dementia.4 Several studies with neurologically healthy individuals have shown that WMHs, especially around the periventricular area, are related to deficits in speed of cognitive processing and attention.5–7 It has been suggested that executive functions mediated by the frontal lobe are particularly vulnerable to the effects of WMHs.8,9 The underlying cause for the observed relationship is assumed to lie in a disruption of the frontal subcortical circuits, which compromises the integrity of the frontal lobe functions.10–12 Nevertheless, the clinical relevance of the location of WMHs is still not well known.
Along with the population based studies, much of the literature on white matter has centred on memory clinic samples and dementia outpatients. A central feature of vascular cognitive impairment and dementia with subcortical small vessel pathology seems to be an impairment of executive functioning.13,14 Previous studies have also indicated that WMHs are an important risk factor for post-stroke dementia,15 together with complex interactions of infarct features and brain atrophy.16 Despite the fact that WMHs are commonly found in stroke patients, studies investigating their specific role in cognitive performance in this population are few. Recently, Burton and co-workers17 suggested that in older stroke patients the volume of WMHs, particularly in the frontal regions, is related to diminished cognitive processing speed and attention, while the volume of temporal lobe hyperintensities is associated with memory impairment. In addition, Sachdev and colleagues18 have reported a correlation between white matter pathology and cognitive dysfunction in patients with stroke or transient ischaemic attack.
The purpose of this study was to explore how the severity and location of WMHs predict performance in neuropsychological tests in elderly stroke patients. In our large stroke cohort, we earlier demonstrated that WMHs are associated with executive dysfunction.19 In this study, we aimed to investigate in further detail the role of WMHs in executive deficits and mental slowing, and the mediating effects of these deficits to other cognitive functions. Periventricular hyperintensities (PVHs) were analysed separately around both frontal (PVH-FH) and occipital horns (PVH-OH), and along the bodies of the lateral ventricles (PVH-B). In addition, the non-periventricular WMHs in deep, watershed, and subcortical areas (WMH-D) were examined. Total infarct volume, general cortical atrophy, and host factors were considered to be covariate predictors of cognition.
METHODS
Patients and study design
The Helsinki Stroke Aging Memory Study is a prospective cross sectional study of elderly patients with ischaemic stroke. The patients were 55 to 85 years of age and they were recruited consecutively at the emergency unit of the Helsinki University Central Hospital, Helsinki, Finland (n = 486). The details of the protocol and cohort have been reported previously.20 The patients went through a clinical assessment, brain MRI, and a comprehensive neuropsychological examination 3 months after the index stroke. In this study, we included patients who succeeded in completing both the neuropsychological test battery and MRI adequately (n = 323). The ethics committee of the Department of Neurology, Helsinki University Central Hospital, approved the study, and all patients participating in the study gave an informed consent.
Neuropsychological examination
The neuropsychological examination was conducted by observers blinded to the neuroradiological data. The test methods are clinically widely established and they were presented according to their standard instructions and scoring. The details have been described in previous reports.21,22
Mental speed
Speed of mental processing and attention were assessed with the Trail Making test part A,23 and a modified short form of the Stroop test (24 items with four colours), the coloured dots section (Stroop dots).24,25 In both of these tests, the time taken to complete the task was recorded. No corrections were made for errors.
Executive functions
The Trail Making test part B,23 and the short form of the Stroop test, coloured colour names section (Stroop words),24,25 were used in evaluating mental flexibility, set shifting, and response inhibition. In both conditions, the time taken to complete the test and the correct responses were recorded. Errors were not corrected. A modified version of the Wisconsin Card Sorting test (WCST)26 was used in assessing abstract problem solving and the ability to shift cognitive sets. The total number of correct responses and perseverative errors were recorded. Verbal fluency was measured in letter generation (letter K) and semantic category (animals), both in 60 seconds,25 and were considered in conjunction with the other executive tests.
Memory functions
Digit span forward and backward tasks were administered according to the Wechsler Memory Scale (WMS)27 in measuring short term storage and working memory. The tasks were included in the final analysis as a sum variable, as they gave identical results. Verbal memory was assessed b