Biomedical subjects

F van Harskamp

Publications and source records attributed to F van Harskamp.

At least 19 recordsLinked to original sources

PubMed2003

Linguistic deficits in the acute phase of stroke.

BACKGROUND AND PURPOSE: For the diagnosis of aphasia early after stroke, several screening tests are available to support clinical judgment. None of these tests enables the clinician to assess the underlying linguistic deficits, i. e. semantic, phonological and syntactic deficits, which provides indispensable information for early therapeutic decisions. The ScreeLing was designed as a screening test to detect semantic, phonological and syntactic deficits. The ScreeLing's sensitivity, specificity and accuracy in detecting aphasia and semantic, phonological and syntactic deficits were determined. METHODS: The ScreeLing was validated in an acute stroke population against a combined reference diagnosis of aphasia (aphasia according to at least two of the following measures:ne urologist's judgment, linguist's judgment, Tokentest-score). The three ScreeLing subtests were validated in the aphasic population against the presence or absence of a semantic, phonological and/or syntactic deficit according to an experienced clinical linguist. RESULTS: From a consecutive series of 215 stroke patients, 63 patients were included. The ScreeLing was an accurate test for the detection of aphasia (0.92),with a sensitivity of 86% and specificity of 96%. Sensitivity of subtests was 62 % for semantics, 54 % for phonology and 42 % for syntax. Specificity was 100 % for semantics and phonology and 80 % for syntax, and accuracy 0.84 for semantics, 0.87 for phonology and 0.64 for syntax. CONCLUSIONS: The ScreeLing is an accurate test that can be easily administered and scored to detect aphasia in the first weeks after stroke. Furthermore, the ScreeLing is suitable for revealing underlying linguistic deficits, especially semantic and phonological deficits.

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PubMed2001

Prognosis of Alzheimer's disease: the Rotterdam Study.

The aim of this study was to construct a prognostic model to predict the progression of Alzheimer's disease (AD). Prevalent and incident cases with AD came from the Rotterdam Study, a population-based prospective cohort study of persons aged 55 years and older, including those living in institutions. Rate of cognitive decline, as measured by the Mini Mental State Examination (MMSE score), was predicted by a random effects model. Risk of institutionalization and death were estimated with polytomous logistic regression analysis. At baseline, 306 subjects were diagnosed with prevalent AD and had complete data on living conditions and cognitive function. After a mean follow-up of 2.1 years, 95 subjects with incident AD had been diagnosed. Prevalent patients showed a slower decline in cognitive function than incident patients (p = 0.004). For prevalent and incident AD patients, high age and low cognitive performance were the strongest predictors for institutionalization and death. These prognostic risk functions can provide information on the decline of Alzheimer patients and might be used to better evaluate the effect of treatments for AD.

Activities of Daily Living↗

PubMed1999

Diabetes mellitus and the risk of dementia: The Rotterdam Study.

OBJECTIVE: To determine the influence of type 2 diabetes mellitus on the risk of dementia and AD. BACKGROUND: Both dementia and diabetes are frequent disorders in elderly people. METHODS: Prospective population-based cohort study among 6,370 elderly subjects. At baseline study participants were examined for presence of diabetes mellitus. Nondemented participants were followed up, on average, for 2.1 years. Incident dementia was diagnosed using a three-step screening and comprehensive diagnostic workup. To complete the follow-up, medical files were studied of persons who could not be reexamined. We estimated relative risks with proportional hazard regression, adjusting for age, sex, and possible confounders. RESULTS: During the follow-up, 126 patients became demented, of whom 89 had AD. Diabetes mellitus almost doubled the risk of dementia (relative risk [RR] 1.9 [1.3 to 2.8]) and AD (RR 1.9 [1.2 to 3.1]). Patients treated with insulin were at highest risk of dementia (RR 4.3 [1.7 to 10.5]). CONCLUSION: The diabetes attributable risk for dementia of 8.8% suggests that diabetes may have contributed to the clinical syndrome in a substantial proportion of all dementia patients.

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PubMed1999

Apolipoprotein E genotype and progression of Alzheimer's disease: the Rotterdam Study.

The APOE*4 allele of the apolipoprotein E gene increases the risk of Alzheimer's disease (AD), but whether it also affects the course of the disease is controversial. However, all studies on this issue until now have been based on patients at various stages of disease. In the present population-based study, 97 patients were included at a similar stage, i.e., before the onset of symptoms, and followed for up to 5 years. We found that the APOE*4 allele is not a strong determinant of survival in AD. As change in cognitive function and severity of dementia are similar for AD patients with and without APOE*4, our study suggests that progression of AD is not related to the APOE*4 allele.

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PubMed1999

Education and the incidence of dementia in a large population-based study: the Rotterdam Study.

We assessed the risk of dementia by educational level in a prospective population-based study. In the Rotterdam Study, 6,827 nondemented participants with known education level were followed for an average of 2.1 years. During this period, 137 new cases of dementia occurred. Low education was associated with higher dementia risk in women but not in men, suggesting that the association is modified by sex. Our data indicate that cross-sectional studies may overrate the association between education and risk of dementia.

Age Distribution↗

PubMed1998

Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study.

BACKGROUND: Previous studies suggested a protective effect of smoking on Alzheimer's disease, but most were case-control studies based on prevalent cases. The findings of prospective studies on the association between smoking and the risk of dementia are inconclusive. METHODS: We did a population-based follow-up study of elderly people who were initially free of dementia. 6870 people aged 55 years and older agreed to take part. Smoking history was taken at baseline and participants were classified as never smokers, former smokers, and current smokers. During follow-up, we recorded all incident cases of dementia. We used never smokers as the reference category to calculate relative risks of dementia and Alzheimer's disease by Cox proportional hazards regression, after adjustment for age, sex, education, and alcohol intake. We also examined modification of risk by age, sex, and the apolipoprotein E (APOE) genotype. FINDINGS: During mean follow-up of 2.1 (range 1.5-3.4) years, 146 incident cases of dementia were detected, of which 105 were Alzheimer's disease. Compared with never smokers, smokers had an increased risk of dementia (relative risk 2.2 [95% CI 1.3-3.6]) and Alzheimer's disease (2.3 [1.3-4.1]). Smoking was a strong risk factor for Alzheimer's disease in individuals without the APOEepsilon4 allele (4.6 [1.5-14.2]), but had no effect in participants with this allele (0.6 [0.1-4.8]). INTERPRETATION: Smoking was associated with a doubling of the risk of dementia and Alzheimer's disease. Our finding that carriers of the APOEepsilon4 had no increased risk of dementia suggests an interaction between smoking and the APOEepsilon4 genotype in the aetiology of Alzheimer's disease.

Age Distribution↗

PubMed1998

Incidence and risk of dementia. The Rotterdam Study.

To assess age-, sex-, and subtype-specific incidence rates of dementia and to calculate the risk of dementia, the authors performed a large, community-based, prospective cohort study on dementia as part of the Rotterdam Study. Participants were recruited among residents of a suburb of Rotterdam, aged 55 years and older. Baseline examinations took place between 1990 and 1993. The average follow-up was 2.1 years. Screening for dementia followed a three-stage protocol. Medical records of subjects who had died or could not be examined in person were evaluated. Of 7,046 subjects who were nondemented at baseline, 162 developed dementia during 15,135 person-years of follow-up, resulting in an overall incidence rate of 10.7 per 1,000 person-years. From the youngest to the oldest 5-year age category, the incidence rate increased from 0.6 to 97.2 per 1,000 person-years. Only in men did the increase level off after age 85. Overall, the incidence rate per 1,000 person-years was 7.7 for Alzheimer's disease and 1.5 for vascular dementia. Dementia incidence rates and dementia-free Kaplan-Meier survival tables were used to calculate age- and sex-specific cumulative risks of dementia. Although the incidence rates of men and women up to age 85 were similar, the lifetime risk of dementia for 55-year-old women was twice as high as for men (0.33 vs. 0.16), reflecting both the higher life expectancy of women and the higher dementia risk at very old age.

Age Distribution↗

PubMed1998

Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala-->Gly mutation.

Mutations at codons 717 and 670/671 in the amyloid precursor protein (APP) are rare genetic causes of familial Alzheimer's disease (AD). A mutation at codon 693 of APP has also been described as the genetic defect in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). We have reported a APP692Ala-->Gly (Flemish) mutation as a cause of intracerebral hemorrhage and presenile dementia diagnosed as probable AD in a Dutch family. We now describe the post-mortem examination of two demented patients with the APP692 mutation. The neuropathological findings support the diagnosis of AD. Leptomeningial and parenchymal vessels showed extensive deposition of Abeta amyloid protein. Numerous senile plaques consisted of large Abeta amyloid cores, often measuring more than 30 microm in diameter and were surrounded by a fine meshwork of dystrophic neurites. In addition, there were a large number of paired helical filaments in pyramidal neurons and dystrophic neurites. Our findings show that the APP692 mutation leads to morphological abnormalities that are similar to AD, but the morphology of senile plaques is clearly distinct from that described in sporadic and chromosome 14-linked AD patients, in patients with APP717 mutations causing familial, presenile AD and in patients with the APP693 mutation causing HCHWA-D.

Alzheimer Disease↗

PubMed1998

Abnormal amino acid metabolism in patients with early stage Alzheimer dementia.

Plasma levels of several amino acids were studied in 14 patients with early stage probable Alzheimer's disease (AD) and 17 age-matched controls. In the AD patients a possible relationship between amino acid levels and behavioural symptomatology was also investigated. We found significantly reduced levels of tryptophan and methionine in plasma samples from the AD patients compared to the control subjects. Moreover, plasma tyrosine/large neutral amino acids (LNAA) ratio and the ratio of plasma taurine and the product of the plasma levels of methionine and serine (TSM-ratio) were significantly increased in the AD patients in comparison with the controls. However, no difference was found in plasma tryptophan/LNAA ratio and in homocysteine levels between both groups. Concerning the behavioural symptomatology no significant correlation was found between the Reisberg Behave AD scale and plasma amino acid levels or ratios. The reported findings suggest that abnormal amino acid metabolism is present in the early stages of AD. We hypothesize that this abnormality could play a role in the pathogenesis of behavioural changes occurring in later stages of AD.

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PubMed1998

Risk of left ventricular dysfunction in patients with probable Alzheimer's disease with APOE*4 allele.

OBJECTIVE: To examine the association between the APOE genotype and cardiovascular disease in Alzheimer's disease (AD) patients. DESIGN: Case register study of 100 consecutive referrals to a Memory Clinic where type of dementia and cardiovascular comorbidity were diagnosed and APOE genotype was determined. SETTING: The Memory Clinic, University Hospital Rotterdam Dijkzigt. PARTICIPANTS: One hundred Memory Clinic patients, 59 to 91 years of age, who attended the Memory Clinic in the period between January 1994 and March 1996. MEASUREMENTS: Relative risk of cardiovascular morbidity in probable AD, based on clinical and ECG findings. RESULTS: The diagnosis of probable AD was more frequent in APOE*4 allele-carrying AD patients. When comparing homozygotes for APOE*4 with homozygotes for APOE*3, a nine-fold increase in prevalence of cardiac ischemia on ECG was found in the former. When grouping parameters of left ventricular dysfunction, the prevalence was 7.2 (95% confidence interval 1.2-42.6) times greater in probable Alzheimer patients with APOE4/4. CONCLUSIONS: In patients with probable AD, APOE*4 is associated with cardiac disease indicative of left ventricular dysfunction.

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PubMed1998

Disturbances of affective prosody in patients with schizophrenia; a cross sectional study.

The objective was to determine whether disturbances of affective prosody constitute part of the symptomatology of schizophrenia. Affective prosody is defined here as a neuropsychological function that encompasses all non-verbal aspects of language that are necessary for recognising and conveying emotions in communication. Twenty six schizophrenic outpatients and twenty four normal controls underwent a standardised prosody test, assessing four different aspects of affective prosody: spontaneous prosody, prosodic recognition, prosodic repetition, and facial affect recognition. Patients scored significantly worse than controls on three of the four subtests: spontaneous prosody, prosodic recognition, and prosodic repetition. There were no significant differences on a subtest for facial affect recognition. Differences in educational level between patients and controls could not account for these differences.

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PubMed1998

The CAMCOG: a useful screening instrument for dementia in stroke patients.

BACKGROUND AND PURPOSE: Most mental screening tests focus on the detection of cognitive deficits compatible with Alzheimer's disease. Stroke patients who develop a dementia syndrome, however, constitute a more heterogeneous group with both cortical and subcortical disturbances. We assessed the diagnostic accuracy of the CAMCOG (the cognitive and self-contained part of the Cambridge Examination for Mental Disorders of the Elderly) and the Mini-Mental State Examination (MMSE) for dementia in patients with a recent stroke. METHODS: In patients aged 55 and older who were admitted in the Rotterdam Stroke Databank, cognitive functioning was assessed between 3 and 9 months after the most recent stroke. The "gold standard" diagnosis of dementia was compatible with the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. The CAMCOG and MMSE scores were obtained independent of the diagnostic procedure. RESULTS: Of 300 consecutive patients, 71 (23.7%) were demented. Sixteen severely demented patients could not be tested and were excluded. The CAMCOG and MMSE scores were significantly related to dementia (both P<0.0001) in a logistic regression model. Receiver operating characteristic analysis showed that the CAMCOG was a more accurate screening instrument (area under the curve for CAMCOG, 0.95; for MMSE, 0.90). Two other clinical variables independently improved the diagnostic accuracy of the MMSE and CAMCOG: patients with a left hemispheric lesion had a lower (odds ratio, 0.3; 95% confidence interval, 0.1 to 0.7), and patients with hemorrhagic stroke had a greater chance of being demented (odds ratio, 3; 95% confidence interval, 1 to 10). The effect of left hemispheric lesion as an independent diagnostic factor could not be explained by selection or its association with aphasia alone. CONCLUSIONS: The CAMCOG is a feasible instrument for use in patients with a recent transient ischemic attack or stroke. It is a more accurate screening tool for dementia than the MMSE, especially when type and site of stroke are taken into account.

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PubMed1997

Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study.

BACKGROUND: Vascular disorders have been implicated in dementia, but whether atherosclerosis is related to the most frequent type of dementia, Alzheimer's disease, is not known. The apolipoprotein-E genotype has been associated with Alzheimer's disease, and we postulate that it plays a part, together with atherosclerosis, in the aetiology of Alzheimer's disease. We investigated the frequency of dementia and its subtypes in relation to atherosclerosis and apolipoprotein E. METHODS: We did a population-based study of 284 patients with dementia, 207 of whom had Alzheimer's disease, and 1698 individuals who were not demented. Indicators of atherosclerosis included vessel wall thickness and plaques of the carotid arteries, assessed by ultrasonography, and the ratio of ankle-to-brachial systolic blood pressure as a measure of generalised atherosclerosis. Based on these indicators participants were scored from 0 (no atherosclerosis) to 3 (severe atherosclerosis) for degree of atherosclerosis. Apolipoprotein-E polymorphisms were assessed in 246 patients and in 928 controls. FINDINGS: All indicators of atherosclerosis were associated with dementia (odds ratios ranging from 1.3 to 1.9) and its major subtypes Alzheimer's disease (odds ratios 1.3-1.8) and vascular dementia (odds ratios 1.9-3.2). The frequencies of all dementia. Alzheimer's disease, and vascular dementia increased with the degree of atherosclerosis. The odds ratio for Alzheimer's disease in those with severe atherosclerosis compared with those without atherosclerosis was 3.0 (95% CI 1.5-6.0; p = 0.001). In participants with the apolipoprotein-E epsilon 4 genotype and an atherosclerosis score of 2 or 3 the odds ratio for all dementia was 4.5 (2.0-10.1; p < 0.001), for Alzheimer's disease was 3.9 (1.6-9.6; p = 0.002), and for vascular dementia was 19.8 (4.1-95.0; p < 0.001). INTERPRETATION: These findings suggest that dementia and its two major subtypes Alzheimer's disease and vascular dementia are associated with atherosclerosis and that there is an interaction between apolipoprotein E and atherosclerosis in the aetiology of Alzheimer's disease.

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PubMed1997

Atrial fibrillation and dementia in a population-based study. The Rotterdam Study.

BACKGROUND AND PURPOSE: Atrial fibrillation is a frequent disorder in the elderly and a known risk factor for cerebrovascular stroke. We investigated the association of atrial fibrillation with dementia and cognitive impairment in a large cross-sectional, population-based study in the elderly. METHODS: Of the 6584 participants in the Rotterdam Study aged 55 to 106 years, detailed information on dementia status and ECG abnormalities was available. Dementia was diagnosed in three phases. First, participants were screened. Screen-positive subjects were tested further. Those with possible dementia underwent an extensive diagnostic workup. Dementia and dementia subtypes were diagnosed according to prevailing criteria. Cognitive impairment was defined as a Mini-Mental State Examination test score of < 26 points for a nondemented subject. RESULTS: Atrial fibrillation was diagnosed in 195, dementia in 276, and cognitive impairment in 635 subjects. We found significant positive associations of atrial fibrillation with both dementia and impaired cognitive function (age- and sex-adjusted odds ratios, 2.3 [95% confidence interval, 1.4 to 3.7] and 1.7 [95% confidence interval, 1.2 to 2.5]), respectively). The strongest association was found not for vascular dementia but rather for Alzheimer's disease with cerebrovascular disease. The associations were stronger in women, and the relation with dementia was more pronounced in the relatively younger elderly. A history of stroke in subjects with atrial fibrillation could not account for these associations. CONCLUSIONS: Dementia and subtypes Alzheimer's disease and vascular dementia may be related to atrial fibrillation even if no clinical stokes have occurred.

Age Factors↗

PubMed1996

Vascular risk factors, atherosclerosis, cerebral white matter lesions and cerebral perfusion in a population-based study.

We studied risk factors for cerebral vascular disease (blood pressure and hypertension, factor VIIc, factor VIIIc, fibrinogen), indicators of atherosclerosis (intima-media thickness and plaques in the carotid artery) and cerebral white matter lesions in relation to regional cerebral blood flow (rCBF) in 60 persons (aged 65-85 years) recruited from a population-based study. rCBF was assessed with single-photon emission tomography using technetium-99m d, l-hexamethylpropylene amine oxime (99mTc-HMPAO). Statistical analysis was performed with multiple linear regression with adjustment for age, sex and ventricle-to-brain ratio. A significant positive association was found between systolic and diastolic blood pressure and temporo-parietal rCBF. In analysis with quartiles of the distribution, we found a threshold effect for the relation of low diastolic blood pressure (</=60 mmHg) and low temporo-parietal rCBF. Levels of plasma fibrinogen were inversely related to parietal rCBF, with a threshold effect of high fibrinogen levels (>3.2 g/l) and low rCBF. Increased atherosclerosis was related to low rCBF in all cortical regions, but these associations were not significant. No consistent relation was observed between severity of cerebral white matter lesions and rCBF. Our results may have implications for blood pressure control in the elderly population.

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PubMed1996

Association of diabetes mellitus and dementia: the Rotterdam Study.

Dementia and non-insulin-dependent diabetes mellitus (NIDDM) are highly prevalent disorders in the elderly. Diabetes has repeatedly been reported to affect cognition, but its relation with dementia is uncertain. We therefore studied the association between diabetes and dementia in the Rotterdam Study, a large population-based study in the elderly. Of 6330 participants, aged 55 to 99 years old, complete information on diabetes and presence of dementia was available. Diabetes was diagnosed as use of anti-diabetes medication or random or post-load serum glucose over 11 mmol/1. Dementia was diagnosed through a stepped approach, including a sensitive screening of all participants and a comprehensive diagnostic work-up. Diabetes was present in 724 (11.4%) subjects. Of the 265 dementia patients 59 (22.3%) had diabetes. Multiple logistic regression analyses, adjusting for age and sex differences, revealed a positive association between diabetes and dementia (odds ratio: 1.3, 95% confidence interval 1.0-1.9). In particular, strong associations were found between dementia and diabetes treated with insulin (odds ratio: 3.2, 95% confidence interval: 1.4-7.5) The relation was strongest with vascular dementia but was also observed with Alzheimer's disease. These associations were independent of educational attainment, smoking, body mass index, atherosclerosis, blood pressure and antihypertensive drug treatment, and could not be explained by clinical cerebra infarctions. The results suggest that NIDDM is associated with dementia. Alzheimer's disease may be more frequent in elderly diabetic patients treated with insulin.

Age Factors↗

PubMed1995

Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study.

OBJECTIVE: To estimate the prevalence of dementia and its subtypes in the general population and examine the relation of the disease to education. DESIGN: Population based cross sectional study. SETTING: Ommoord, a suburb of Rotterdam. SUBJECTS: 7528 participants of the Rotterdam study aged 55-106 years. RESULTS: 474 cases of dementia were detected, giving an overall prevalence of 6.3%. Prevalence ranged from 0.4% (5/1181 subjects) at age 55-59 years to 43.2% (19/44) at 95 years and over. Alzheimer's disease was the main subdiagnosis (339 cases; 72%); it was also the main cause of the pronounced increase in dementia with age. The relative proportion of vascular dementia (76 cases; 16%), Parkinson's disease dementia (30; 6%), and other dementias (24; 5%) decreased with age. A substantially higher prevalence of dementia was found in subjects with a low level of education. The association with education was not due to confounding by cardiovascular disease. CONCLUSIONS: The prevalence of dementia increases exponentially with age. About one third of the population aged 85 and over has dementia. Three quarters of all dementia is due to Alzheimer's disease. In this study an inverse dose-response relation was found between education and dementia--in particular, Alzheimer's disease.

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PubMed1994

The apolipoprotein E epsilon 4 allele does not influence the clinical expression of the amyloid precursor protein gene codon 693 or 692 mutations.

In 31 symptomatic and 5 asymptomatic carriers of the amyloid precursor protein (APP) gene codon 693 mutation, 10 family members without mutation, and 5 carriers of the APP gene codon 692 mutation (3 with early-onset Alzheimer dementia, 2 with cerebral hemorrhage), a high frequency of the apolipoprotein E epsilon 4 allele was found. Age at onset, age at death, occurrence of dementia, and number of strokes did not differ between APP gene mutation carriers with or without epsilon 4 allele, showing that the clinical expression of these APP mutations is not influenced by the apolipoprotein E gene.

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