Biomedical subjects

Huub A M Middelkoop

Publications and source records attributed to Huub A M Middelkoop.

9 recordsLinked to original sources

PubMed2006

Perception of emotional facial expressions at different intensities in early-symptomatic Huntington's disease.

BACKGROUND: While there is abundant evidence that patients with Huntington's disease (HD) have an impairment in the recognition of the emotional facial expression of disgust, previous studies have only examined emotion perception using full-blown facial expressions. OBJECTIVE: The current study examines the perception of facial emotional expressions in HD at different levels of intensity to investigate whether more subtle deficits can be detected, possible also in other emotions. METHOD: We compared early symptomatic HD patients with healthy matched controls on emotion perception, presenting short video clips of a neutral face changing into one of the six basic emotions (happiness, anger, fear, surprise, disgust and sadness) with increasing intensity. Overall face perception ability as well as depressive symptoms were taken into account. RESULTS: A specific impairment in recognizing the emotions disgust and anger was found, which was present even at low emotion intensities. CONCLUSION: These results extend previous findings and support the use of more sensitive emotion perception paradigms, which enable the detection of subtle neurobehavioral deficits even in the pre- and early symptomatic stages of the disease.

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PubMed2006

Focusing on vigilance instead of sleepiness in the assessment of narcolepsy: high sensitivity of the Sustained Attention to Response Task (SART).

STUDY OBJECTIVE: The severity of narcolepsy is commonly measured with the Multiple Sleep Latency Test (MSLT), focusing on the tendency to fall asleep. A neglected but perhaps equally important complaint is impaired performance in the waking state. We evaluated the Sustained Attention to Response Task (SART) for the quantification of vigilance in narcolepsy. DESIGN: The SART involves withholding key presses to 1 in 9 target stimuli. In the present study, it was administered prior to each of 5 MSLT sessions in a 1-day study. The Epworth Sleepiness Scale was administered to measure subjective sleepiness. SART and MSLT results (number of errors and sleep latency) were compared using Receiver Operator Curves, sensitivity, and specificity. SETTING: Tertiary narcolepsy referral center in a university hospital. PATIENTS: Fifteen untreated narcoleptics and 15 matched controls. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The area under the receiver operating curve was 0.97 for the MSLT and 0.95 for the SART. Sensitivity and specificity for the MLST were 80% and 100% using a cutoff point of 5 minutes. For the SART, these values were 87% and 100%, using a 5-error cutoff. The SART and MSLT showed no correlation with each other or with the Epworth Sleepiness Scale. CONCLUSIONS: The SART, measuring attention, was abnormal as often as the MSLT, measuring sleepiness. The inability to remain vigilant during the day may be the most serious complaint in narcolepsy, since it impairs performance. The SART is valid in this respect, is easy to administer, and takes little time.

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PubMed2005

Late-onset dementia: structural brain damage and total cerebral blood flow.

PURPOSE: To prospectively compare indicators of structural brain damage and total cerebral blood flow in patients with late-onset dementia, subjects of the same age with optimal cognitive function, and young subjects. MATERIALS AND METHODS: The institutional ethics committee approved the studies, and all participants (or their guardians) gave informed consent. The test group included 17 patients older than 75 years (four men, 13 women; median age, 83 years) and with a diagnosis of dementia according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The control group included 16 subjects (four men, 12 women; median age, 87 years) with optimal cognitive function, who were selected from among 599 elderly subjects enrolled in a population-based follow-up study, and 15 young healthy subjects (seven men, eight women; median age, 29 years). Measurements of intracranial and total brain volumes, structural brain damage, and cerebral blood flow were obtained with magnetic resonance imaging. Mean values were compared with the t test; medians, with the Mann-Whitney U test. RESULTS: Values for total brain volume were significantly smaller in elderly subjects (P < .001) but did not differ significantly between patients with dementia and subjects of the same age with optimal cognitive function (P = .69). Among the elderly, significantly higher scores for number and extent of white matter areas of signal hyperintensity (P = .028) and lower magnetization transfer ratios (P = .016) indicated greater structural brain damage in those with dementia. Cerebral blood flow was 246 mL/min lower (P < .001) in elderly subjects than in young subjects. In patients with dementia, cerebral blood flow was 108 mL/min lower than that in subjects of the same age with optimal cognitive function (551 vs 443 mL/min, P < .001). CONCLUSION: The combined observations of more structural brain damage and lower cerebral blood flow in demented elderly individuals than in subjects of the same age with optimal cognitive function support the hypothesis that vascular factors contribute to dementia in old age.

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PubMed2005

Neuropsychological correlates of MRI measures in the continuum of cognitive decline at old age.

OBJECTIVE: To investigate the independent associations between medial temporal lobe atrophy and white matter hyperintensities (WMH) and cognitive functions in the elderly. METHODS: Cognitive functions of 41 Alzheimer's disease patients, 20 patients with mild cognitive impairment and 28 elderly subjects without memory complaints were assessed using a neuropsychological test battery. Quantitative MRI measures of medial temporal lobe volume and WMH were obtained. Multiple regression analyses were performed to assess the independent contribution of MRI measures to impairment in several cognitive functions. RESULTS: Scores on the Wechsler Memory Scale and Trails B depended selectively on medial temporal lobe volume, whereas WMH selectively contributed to performance on Trails A. Medial temporal lobe volume and WMH both contributed to scores on the Cambridge Cognitive Examination and the Boston naming task. CONCLUSIONS: MRI measures suggestive of Alzheimer-type pathology and microvascular pathology independently contribute to cognitive decline at old age. Memory impairment as measured using the Wechsler Memory Scale and performance on Trails B primarily depended on medial temporal lobe atrophy. Psychomotor slowness, as measured using Trails A, mainly depended on WMH. These results suggest that vascular pathology and Alzheimer-type pathology each have specific cognitive correlates.

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PubMed2005

MRI measures and progression of cognitive decline in nondemented elderly attending a memory clinic.

OBJECTIVE: To investigate whether MRI-based volumes of whole brain, medial temporal lobe and white matter hyperintensities (WMH) predict progression of cognitive decline in a sample of nondemented elderly. METHODS: Thirty-seven nondemented elderly attending a memory clinic and 28 elderly controls participated in this follow-up study. The average follow-up period was 1.8 years. Cognitive function was measured at baseline and follow-up with the Cambridge Cognitive Examination (CAMCOG). Baseline Magnetic Resonance Imaging (MRI) provided quantitative measures of whole brain, medial temporal lobe and WMH. Linear mixed models controlled for age and sex were used to assess the independent associations between MRI measures, baseline cognition, and annual decline in cognition. RESULTS: Medial temporal lobe volume was independently associated with baseline CAMCOG score (p < 0.01), whereas whole brain volume (p < 0.01) and WMH (p < 0.05) were associated with annual decline in CAMCOG score. CONCLUSIONS: These data suggest that regional damage to the medial temporal lobes underlies initial mild cognitive impairment, whereas more global brain changes, such as whole brain atrophy and WMH, contribute to further progression of cognitive decline.

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PubMed2004

Objective assessment of motor slowness in Huntington's disease: clinical correlates and 2-year follow-up.

Functional disability of patients with Huntington's disease (HD) is determined by impairment of voluntary motor function rather than the presence of chorea. However, only few attempts have been made to quantify this motor impairment. By using a simple reaction time paradigm, we measured the time needed for movement initiation (akinesia) and execution (bradykinesia) in 76 HD patients and 127 controls. Akinesia and bradykinesia were already evident in early stages and increased linearly with increasing disease stage. Quantified motor slowness correlated with clinical impairment of voluntary movements but also with cognitive impairment and medication use. In patients without severe cognitive impairment, quantified motor slowness reflected clinical motor impairment more purely. During 1.9 years follow-up (range, 0.8-3.8 years), quantified akinesia and bradykinesia progressed concomitantly with progression of clinical impairment of voluntary movements, cognition, and functional capacity. However, rate of change in motor slowness did not discriminate between patients whose disease stage remained stable and those whose disease stage progressed. We conclude that the reaction time paradigm may be used to quantify akinesia and bradykinesia in HD, at least in patients without severe cognitive impairment. Although reaction and movement times increased in time, these measures failed to detect functionally important changes during our follow-up period.

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PubMed2004

Memory complaints in patients with normal cognition are associated with smaller hippocampal volumes.

We aimed to investigate volumetry of the medial temporal lobe in patients with subjective memory complaints without any cognitive impairment. This study included 20 patients with subjective memory complaints and normal cognitive function and 28 controls without memory complaints. Volumes of the hippocampus and parahippocampal gyrus (PHG) were measured using coronal T1-weighted MR images. Cognitive functions were assessed using the Cambridge Cognitive Examination. Depressive symptoms were assessed using the Geriatric Depression Scale. Differences between groups were analysed using t-tests. Patients with subjective memory complaints had a higher education and more depressive symptoms than controls ( p < 0.01). Moreover, they had smaller left hippocampal volumes than controls ( p < 0.01). There were no differences between groups in the volume of the right hippocampus or PHG. There was a moderate association between the volume of left hippocampus and left PHG and memory-score (r = 0.32, p = 0.03; r = 0.34, p = 0.02). We concluded that memory complaints in patients without any cognitive impairment were associated with smaller left hippocampal volumes and more depressive symptoms. These preliminary results suggest that memory complaints may reflect minimal brain deficits associated with impending dementia, depression or a combination of both disorders.

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PubMed2003

Incipient CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Knowledge of disease expression in young adult NOTCH3 mutation carriers (MCs) is limited. OBJECTIVE: To characterize clinical, neuropsychological, and radiological status in NOTCH3 MCs younger than 35 years. DESIGN: Clinical characterization and blinded survey comparing MCs with non-MCs. SETTING: Referral center. PARTICIPANTS: Individuals younger than 35 years who were at a 50% risk of a NOTCH3 mutation, from our CADASIL database. Thirteen individuals, from 8 families, met the criteria. METHODS: Comprehensive clinical, genetic, neuropsychological, and radiological investigations. Magnetic resonance images were scored according to a standardized white matter hyperintensities rating scale. RESULTS: Six individuals, from 5 families, were MCs. Clinical symptoms consisted of migraine (with aura), stroke, and stroke-like episodes. We did not find evidence for psychiatric disturbances, functional disability, or cognitive dysfunction, compared with non-MCs. Radiologically, a characteristic magnetic resonance imaging lesion pattern emerged for all MCs. This comprised white matter hyperintensities in the anterior temporal lobes, the frontal lobes, and the periventricular frontal caps. CONCLUSIONS: Migraine (with aura) and stroke can present in NOTCH3 MCs younger than 35 years; however, more importantly, physical function and cognition are intact. Possible subtle cognitive dysfunction needs to be assessed in a larger study. White matter hyperintensities on magnetic resonance imaging are characteristic, and are consistently visualized from the age of 21 years and onward. Awareness of the clinical and radiological features of CADASIL in those younger than 35 years should increase early diagnosis and allow for customized counseling of young adults from families with CADASIL.

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PubMed2002

Magnetization transfer imaging in normal aging, mild cognitive impairment, and Alzheimer's disease.

The purpose of this study was to assess whether structural brain damage as detected by volumetric magnetization transfer imaging (MTI) is present in mild cognitive impairment (MCI) and Alzheimer's disease (AD) and, if so, whether these abnormalities are global in character or restricted to the temporal lobe. Volumetric MTI analysis of the whole brain and temporal and frontal lobes was performed in 25 patients with probable AD, in 13 patients with MCI, and in 28 controls. Magnetization transfer ratio (MTR) histograms were produced, from which we derived measures for structural brain damage and atrophy. The peak heights of the MTR histograms of MCI and AD patients were lower than those of controls for the whole brain and temporal and frontal lobes, reflecting structural brain damage. AD patients had more atrophy than controls in all regions that were studied. MCI patients differed from controls for temporal lobe atrophy only. Volumetric MTI demonstrates structural changes that are related to cognitive decline in large parts of the brain of AD patients. Moreover, structural changes also were observed in MCI patients, indicating that widespread brain damage can be demonstrated before patients are clinically demented.

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