Biomedical subjects

F Jessen

Publications and source records attributed to F Jessen.

At least 19 recordsLinked to original sources

PubMed2002

In-vivo proton MR-spectroscopy of the human brain: assessment of N-acetylaspartate (NAA) reduction as a marker for neurodegeneration.

Proton magnetic resonance spectroscopy ((1)H-MRS) is a non-invasive method to investigate changes in brain metabolite composition in different cerebral diseases. We performed proton spectroscopy in patients with dementia of the Alzheimer's type (AD) and in patients with motor neuron disease (MND) with the aim to detect the specific metabolic pattern for these neurodegenerative disorders. In the MND group we found a significant reduction of NAA/tCr metabolite ratios in the motor cortex, which correlates with the disease severity and the clinical lateralization of neurological symptoms and further decreases in the time course of the disease. In AD patients a reduction of NAA/tCr was observed in the medial temporal lobe. Since NAA is exclusively expressed in neurons as shown by immunohistochemical studies, reduced NAA levels suggest neuronal loss or dysfunction in the observed regions. The observed regional metabolic alterations reflect the neuronal basis of the characteristic neurological symptoms in AD (dementia) and MND (muscular palsy) and mirrors the disease progress over time.

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PubMed2002

Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease.

Cholesterol and 24S-hydroxycholesterol are involved in the pathogenesis of Alzheimer's disease (AD). Increased serum cholesterol concentrations have been detected in patients with AD. 24S-Hydroxycholesterol is the primary cholesterol elimination product of the brain and possesses neurotoxic properties in vitro. The enzyme catalyzing the conversion of cholesterol to 24S-hydroxycholesterol, cholesterol 24S-hydroxylase (CYP46), is mainly expressed in neurons. Concentrations of 24S-hydroxycholesterol in cerebrospinal fluid (CSF) and serum differ significantly between AD patients and non-demented subjects. To test the hypothesis if polymorphisms in the CYP46 gene might influence the function of the respective enzyme and thus cholesterol metabolism in the human brain, we screened for polymorphisms in 114 AD patients and 144 healthy controls. Two intronic single nucleotide polymorphisms were observed and their allelic distribution was investigated. In our study sample, carriers of the C allele of the IVS3+43C --> T polymorphism were more prevalent in the group of AD patients than in healthy controls, while another IVS2-150A --> G polymorphism did not show a significant association with AD. The CC genotype of the IVS3+43C --> T polymorphism was associated with an increased 24S-hydroxycholesterol/cholesterol ratio in the CSF of AD patients. Our results indicate that the CYP46 gene locus may predispose to AD by increasing the 24S-hydroxycholesterol/cholesterol ratio in the brain.

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PubMed2001

Decrease of N-acetylaspartate in the MTL correlates with cognitive decline of AD patients.

In this (1)H-MRS follow-up study of the medial temporal lobe (MTL) in patients with AD, the authors report a correlation of N-acetylaspartate (NAA)/creatine (Cr) with cognitive decline. Severely progressed patients showed a reduction, whereas stable or mildly progressed subjects showed a slight increase of NAA/Cr. The reduction of NAA/Cr in the MTL represents a correlate of cognitive deterioration in AD, whereas it is of limited use to detect subtle changes over time in clinically stable patients.

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PubMed2001

Amplitude reduction of the mismatch negativity in first-degree relatives of patients with schizophrenia.

First-degree relatives of schizophrenic patients display alterations in various cognitive domains and their electrophysiological counterparts similar to schizophrenic subjects. The mismatch negativity (MMN) is an event-related potential that reflects sensory memory in the pre-attentive stage of auditory processing. An amplitude reduction of the MMN has been reported in schizophrenia. The present study investigated the MMN in patients with schizophrenia, first-degree relatives and control subjects. The MMN amplitude was reduced in relatives compared to controls. The MMN amplitude reduction in schizophrenic patients compared to controls, however, did not reach significance in the present study. These results provide first evidence for disturbed sensory memory in relatives of patients with schizophrenia.

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PubMed2001

A family study of Alzheimer disease and early- and late-onset depression in elderly patients.

BACKGROUND: The substantial symptomatic overlap between depression and dementia in old age may be explained by common genetic vulnerability factors. METHODS: We investigated this idea by comparing the occurrence of both disorders in first-degree relatives of 78 patients with Alzheimer disease (AD), of 74 with late-onset depression (onset age of > or = 60 years), of 78 with early-onset depression, of 53 with comorbid lifetime diagnoses of AD/depression, and of 162 population control subjects. Diagnostic information on their 3002 relatives was obtained from structured direct assessments and from family history interviews. RESULTS: The 90-year lifetime incidence of primary progressive dementia was significantly higher in relatives of patients with AD (30%) and comorbid AD/depression (27%) than in relatives of patients with early-onset (21%) or late-onset (26%) depression, or of controls (22%) (P =.01). Lifetime incidence of depression was significantly higher in relatives of patients with early-onset depression (13%) than in relatives of patients with AD (10%) or controls (9.0%) (P =.006). Lifetime incidence of depression was similar in control relatives and in relatives of those patients with comorbid AD/depression (8.6%). Relatives of patients with late-onset depression also showed similar occurrence of depression until the age of 80 years, but the figure increased sharply thereafter to 19.1% by the age of 90 years. CONCLUSIONS: Primary progressive dementia and early-onset depression represent clinical entities with distinct inheritance. Late-onset depression does not share substantial inheritance in common with dementia or with early-onset depression, but does show modest familial clustering.

Age Factors↗

PubMed2001

Validity of the five-item WHO Well-Being Index (WHO-5) in an elderly population.

BACKGROUND: Depression has a high prevalence in the elderly population; however it often remains undetected. The WHO 5-item Well-Being Index (WHO-5) is a short screening instrument for the detection of depression in the general population, which has not yet been evaluated. The goals of the present study were: 1) to assess the internal and external validity of WHO-5 and 2) to compare the two recent versions of WHO-5. STUDY POPULATION AND METHODS: 367 subjects above 50 years of age were examined with the WHO-5. ICD-10 diagnoses were made using a structured interview (CIDI). The internal validity of the well-being index was evaluated by calculating Loevinger's and Mokken's homogeneity coefficients. External validity for detection of depression was evaluated by ROC analysis. RESULTS: The scale was sufficiently homogeneous (Loevinger's coefficient: version 1 = 0.38, version 2 = 0.47; Mokken coefficient > 0.3 in nearly all items). ROC analysis showed that both versions adequately detected depression. Version 1 additionally detected anxiety disorders, version 2 being more specific for detection of depression. CONCLUSION: The WHO-5 showed a good internal and external validity. The second version is a stronger scale and was more specific for the detection of depression. The WHO-5 is an useful instrument for identifying elderly subjects with depression.

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PubMed2001

Inter-rater reliability of family history information on psychiatric disorders in relatives.

The family history method in psychiatric family studies is an important and necessary way of obtaining information on family members who are not available for personal interview. Studies on the validity of this method have shown that family history information on psychiatric disorders in relatives is neither accurate nor sensitive but highly specific. However, its inter-rater reliability has rarely been assessed, even though this is a prerequisite for adequate validity. In the present investigation we examined the inter-rater reliability of family history information obtained with a semi-structured and symptom-oriented interview. Forty informants were interviewed twice by two different raters within 3 and 20 days. The inter-rater reliability was found to be good for dementia (kappa=0.82, 95% CI=0.61-1.00), alcohol related disorders (kappa=0.93, 95% CI=0.80-1.00), for depressive disorders (kappa=0.72, 95% CI=0.42-1.00), anxiety disorders (kappa=0.75, 95% CI=0.41-1.00) and any psychiatric disorder (kappa=0.79, 95% CI=0.66-0.91). We concluded that the family history interview is a useful family study instrument that can be applied reliably by different raters for frequent psychiatric disorders.

Adult↗

PubMed2001

Encoding and retrieval related cerebral activation in continuous verbal recognition.

The differential neuronal activation related to encoding of novel and recognition of previously studied items and the effect of retrieval effort on neuronal activation were assessed in a event-related functional magnetic resonance imaging experiment. A verbal continuous recognition task with two repetitions of the target items was used. The interpretation of the results was focused on brain areas that have been previously reported to be involved in explicit memory. Encoding of novel words in comparison with the first repetition was associated with a stronger activation in the left parahippocampal and inferior frontal gyrus. Encoding of novel words compared to the second repetition was related to a greater bifrontal activation. Recognition of studied items was associated with greater activation in the medial and bilateral inferior parietal lobe at first repetition and in the medial and left inferior parietal lobe at second repetition in comparison with encoding of the novel items. Recognition at first repetition compared to recognition at second repetition was associated with greater bilateral frontal activation. The results are discussed in relation to current concepts of spatial differentiation of memory function and findings from event-related potentials studies of continuous recognition.

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PubMed2001

Cytochrome oxidase as an indicator of ice storage and frozen storage.

The potential of cytochrome oxidase as an indicator of ice storage and frozen storage of fish was investigated. Optimal assay conditions for cytochrome oxidase in a crude homogenate from cod muscle were studied. Maximal cytochrome oxidase activity was found at pH 6.5-7.5 and an assay temperature of 30 degrees C. Maximal activation by Triton X-100 was obtained in a range of 0.62-1.25 mM Triton X-100. The specificity of the assay was high, as cytochrome oxidase was inhibited 98% by 33 microM of the specific inhibitor sodium azide. The coefficient of variation of cytochrome oxidase activity in different cods was 21%, and the coefficient of variation of different analyses on the same homogenate was 5%. It was shown that ice storage of muscle samples before they were frozen and thawed resulted in a major freezing-induced activation of cytochrome oxidase activity. The enzyme may therefore be used as an indicator of frozen fish to determine if the fish has been stored on ice before freezing. Cytochrome oxidase activity showed also potential as an indicator of frozen storage, as it was possible to distinguish between the frozen storage temperatures -9, -20, and -40 degrees C.

Animals↗

PubMed2001

Sensory gating deficit expressed by a disturbed suppression of the P50 event-related potential in patients with Alzheimer's disease.

OBJECTIVE: Disturbed sensory gating has been related to attention deficit and greater distractibility in patients with schizophrenia, and dysfunction of the alpha-7 subunit of the cholinergic nicotinic receptor has been discussed as its biological basis. Alzheimer's disease is characterized by a cholinergic deficit, and postmortem studies have reported alpha-7 receptor loss in patients with Alzheimer's disease. In this study, the authors tested whether sensory gating is disturbed in patients with Alzheimer's disease. METHOD: Suppression of the P50 event-related potential following the second click of a double-click paradigm, a measure of sensory gating, was assessed in 17 Alzheimer's disease patients and 17 comparison subjects. RESULTS: Alzheimer's disease patients showed less P50 suppression following the second click relative to the comparison subjects. CONCLUSIONS: Disturbed sensory gating might result from cholinergic dysfunction and possibly from alpha-7 nicotinic receptor loss in patients with Alzheimer's disease. Prospective studies should investigate the relationship between sensory gating deficit and behavioral disturbances in Alzheimer's disease patients.

Acoustic Stimulation↗

PubMed2000

Identical distribution of the alpha 2-macroglobulin pentanucleotide deletion in subjects with Alzheimer disease and controls in a German population.

Recently, an association between a deletion polymorphism in the alpha 2-macroglobulin gene (A2M) and Alzheimer disease (AD) has been reported. The aim of the present study was to corroborate this association in a German population of 102 AD patients and two control samples of 191 healthy subject and 160 depressed patients. The frequency of the A2M genotype in AD patients was almost identical to that in both control samples. Logistic regression analysis revealed an effect of age and the APOE genotype on AD risk, but no effect of the A2M genotype. Our findings do not support the fact that the previously reported positive association between A2M deletion polymorphism and AD modifies the disease risk in the studied population. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:775-777, 2000.

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PubMed2000

Response-related fMRI analysis during encoding and retrieval revealed differences in cerebral activation by retrieval success.

The aim of the study was to identify cerebral activation associated with sufficient or insufficient encoding, and with correct or false recognition. Fourteen volunteers performed two paradigms: explicit learning of words; and later retrieval of previously presented words. Items were classified according to the subjects' recognition performance. Echo-planar MRI of blood-oxygen-level-dependent signal changes was performed during encoding and retrieval. Response-related fMRI-analysis was used to compare activation associated with the subjects' retrieval success. During encoding, there was a trend towards increased activation of the left medial cingulate gyrus and of the right fusiform gyrus for later hits (correctly identified, learned target words) in comparison with misses (non-identified targets). During recognition, signal intensities associated with false alarms (falsely identified distractors) were significantly higher in left and right extrastriate cortex than those associated with hits, misses and correct rejections of distractors. Activation in the anterior cingulate gyrus during retrieval was related to reaction time and might be associated with the preparation or performance of motor response. Increased activation during false alarms might reflect a source-monitoring deficit or an increased subjective familiarity with distractors that have been most intensively processed in extrastriate visual cortex.

Adult↗

PubMed2000

Proton MR spectroscopy detects a relative decrease of N-acetylaspartate in the medial temporal lobe of patients with AD.

BACKGROUND: The reduction of N-acetylaspartate (NAA) detected by proton MR spectroscopy (1H-MRS) represents a robust but unspecific marker for neuronal loss or dysfunction. OBJECTIVE: To apply 1H-MRS in two brain regions that reflect the characteristic spatial distribution of neuronal loss in AD. These regions are the medial temporal lobe (MTL), which is affected early in AD, and the primary motor and sensory cortex (central region), which is affected late in the disease and might serve as an intraindividual control region in mild to moderate disease stages. METHODS: Twenty patients and 18 volunteers underwent 1H-MRS in both brain areas. The metabolic ratios of NAA/creatine and choline/creatine were determined. Additionally, the metabolic ratios of the MTL were divided by the ratios of the central region to assess the relative change in the MTL in individual subjects. All ratios were correlated with psychometric test scores. RESULTS: A significant reduction of NAA/creatine and choline/creatine ratios was detected in the MTL of patients with AD. In the central region, no significant difference between the groups was found. NAA/creatine (MTL/central region) was reduced in patients with AD and showed a correlation with the Mini-Mental State Examination and the cognitive part of the Alzheimer Disease Assessment Scale scores. Choline/creatine (MTL/central region) did not show a significant difference between groups. CONCLUSION: Assessing the distribution of NAA/creatine reduction guided by the expected neuropathologic change can improve the role of 1H-MRS in the assessment of AD. The disease severity can be monitored by relative reduction of NAA/creatine in the MTL in comparison with an intraindividual unaffected control region.

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PubMed2000

Allelic association between the D10S1423 marker and Alzheimer's disease in a German population.

Recently a full genome survey detected an allelic association between Alzheimer's disease (AD) and the D10S1423 marker on chromosome 10p12-14 (40 cM from the telomere). In this study we examined the D10S1423 marker in an ethnically homogeneous German population of 80 AD patients and two groups of controls, 168 healthy subjects and 149 depressed patients. The 234-bp allele of the D10S1423 marker showed a significant association with AD (P = 0.033). In conclusion, our results support that the D10S1423 marker is associated with an increased AD risk and provides further evidence for an AD susceptibility locus on chromosome 10.

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PubMed2000

Plasma 24S-hydroxycholesterol: a peripheral indicator of neuronal degeneration and potential state marker for Alzheimer's disease.

The conversion of brain cholesterol into 24S-hydroxycholesterol and its subsequent release into the periphery is probably an important step for the maintenance of brain cholesterol homeostasis. Recent findings suggest that plasma 24S-hydroxycholesterol may be elevated in Alzheimer's disease (AD) and vascular dementia at least at some stage of the disease, suggesting increased brain cholesterol turnover during neurodegeneration. We investigated whether plasma 24S-hydroxycholesterol concentrations depend on the severity of AD and on the apolipoprotein E (apoE) genotype. Severity of AD and inheritance of the apoE4 allele were independently associated with reduced plasma 24S-hydroxycholesterol/cholesterol ratios. The results suggest that the decrease of plasma 24S-hydroxycholesterol/cholesterol in severely affected AD patients is a peripheral marker for loss of cholesterol 24S-hydroxylase in the CNS. Inheritance of the apoE4 allele may be associated with increased apoE-mediated transport of brain cholesterol to the periphery or with decreased activity of the 24S-hydroxylase. Longitudinal studies will assess the validity of the ratio plasma 24S-hydroxycholesterol/cholesterol as a state marker for AD.

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PubMed2000

Association between an interleukin-6 promoter and 3' flanking region haplotype and reduced Alzheimer's disease risk in a German population.

Several studies have demonstrated that interleukin-6 (IL-6) is involved in the pathogenesis of Alzheimer's disease (AD). We previously reported on an association between the C allele of a variable number of tandem repeat polymorphism in the 3' flanking region of IL-6 gene (IL-6vntr) and delayed initial onset and reduced AD risk. A novel G/C polymorphism at position -174 in the IL-6 gene promoter (IL-6prom) has recently been identified and appears to influence the regulation of IL-6 expression. We examined this functional polymorphism in 102 AD patients and two control groups of 191 healthy subjects and 160 depressed patients. There was no evidence for an allelic association between IL-6prom polymorphism and earlier age of onset or risk of AD. However, haplotype analysis showed a strong linkage disequilibrium between IL-6vntr and IL-6prom and demonstrated an interaction between IL-6vntr and IL-6prom which modifies AD risk.

Alleles↗

PubMed2000

The concreteness effect: evidence for dual coding and context availability.

The term concreteness effect refers to the observation that concrete nouns are processed faster and more accurately than abstract nouns in a variety of cognitive tasks. Two models have been proposed to explain the neuronal basis of the concreteness effect. The dual-coding theory attributes the advantage to the access of a right hemisphere image based system in addition to a verbal system by concrete words. The context availability theory argues that concrete words activate a broader contextual verbal support, which results in faster processing, but do not access a distinct image based system. We used event-related fMRI to detect the brain regions that subserve to the concreteness effect. We found greater activation in the lower right and left parietal lobes, in the left inferior frontal lobe and in the precuneus during encoding of concrete compared to abstract nouns. This makes a single exclusive theory unlikely and rather suggests a combination of both models. Superior encoding of concrete words in the present study may result from (1) greater verbal context resources reflected by the activation of left parietal and frontal associative areas, and (2) the additional activation of a non-verbal, perhaps spatial imagery-based system, in the right parietal lobe.

Adult↗

PubMed2000

Interindividual variation of cerebral activation during encoding and retrieval of words.

The aim of the present study was to compare the cerebral activation associated with encoding and retrieval in individual subjects with the average activation in the same group of subjects. Twelve volunteers performed two paradigms: 1) intentional encoding of words, and 2) recognition of learned words intermixed with new distracters. Echo-planar magnetic resonance imaging (MRI) of BOLD signal changes was used to compare cerebral activation between active and resting conditions. During encoding, activation of the left precentral gyrus related to the motor response was observed in some subjects. Averaged data showed increased activation of the left precentral gyrus, the supplementary motor area (SMA), the left inferior frontal gyrus and in the left temporo-occipital junction. During recognition, motor response-related activity was found in the precentral cortex and SMA in most subjects. Activation in other brain areas showed considerable interindividual variation. In the entire group, recognition showed activation of the left dorsolateral prefrontal cortex, the precentral gyrus, the SMA, and the temporo-occipital junction. The total amount and the distribution of task-related cerebral activation varies considerably between individuals and might correspond to individual preferences of cognitive strategies. The investigation of these interindividual variations will be an exciting scientific challenge in the near future.

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