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Biomedical subjects

J Diehl

Publications and source records attributed to J Diehl.

At least 19 recordsLinked to original sources

[Misdemeanor in frontotemporal dementia].

The nature and prevalence of misdemeanor in patients with dementia due to frontotemporal lobar degeneration has been described in a few case reports and in two small U.S. studies. Our clinical impression suggests that antisocial and aggressive behaviour are relatively frequent in this patient population. The objective of the present study was to verify this observation. For this purpose we developed a standardized questionnaire on misdemeanor in Frontotemporal Dementia. Using this instrument caregivers of 30 patients with Frontotemporal Dementia (FTD), 11 patients with Semantic dementia (SD) and 33 patients with Alzheimer-type dementia (AD) were interviewed. The interview included questions about theft, burglary, damaging other peoples' belongings, verbal or physical offence, bodily harm, drug abuse and use of weapons. Questions about the frequency of criminal behaviour, the amount of damages and consequences if applicable completed the questionnaire. Misdemeanor was found in half of the patients with FTD (15 out of 30) and in 7 out of 11 patients with SD, but only in one out of 33 patients with AD. The most frequent type of inappropriate behaviour was theft (13 patients), particularly shoplifting. 8 patients with FTD, 1 patient with SD and 1 patient with AD entered someone else's house without permission. 10 patients with FTD and 3 patients with SD but none of the patients with AD had physically threatened spouses, relatives or strangers. In one case another person was hurt.

Adult↗

[Efficacy of caregiver support groups for dementia].

Counseling of caregivers is an essential component of the management of patients with dementia. According to the empirical research in this field, peer-led self-help groups have the potential to improve subjective outcomes including emotional support, social contact, and control over one's life and thus may facilitate caregiving and reduce psychological burdens. Self-help groups have not been shown, however, to modify objective outcomes such as the time spent for care or the frequency of nursing home admissions. The outcomes of counseling programmes led by professionals depend on the focus of intervention and may include benefits in psychological and psychosomatic symptoms, coping with stress, and managing behavioural disturbances. Studies in the U.S., Australia, and Finland have demonstrated that multimodal counseling programmes led by professionals significantly reduce the number of nursing home admissions and therefore may have considerable importance for health economics.

Caregivers↗

Frontotemporal dementia, semantic dementia, and Alzheimer's disease: the contribution of standard neuropsychological tests to differential diagnosis.

CERAD-NAB (Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery) data were compared between 51 patients with frontotemporal dementia, 13 with semantic dementia, and 69 with Alzheimer's disease. There were statistically significant differences between the 3 groups. Compared with patients with Alzheimer's disease, patients with frontotemporal dementia were more impaired on Animal Fluency but not on any other CERAD-NAB subtest. Patients with semantic dementia performed worse in Animal Fluency and Boston Naming Test compared with frontotemporal dementia and Alzheimer's disease. Multiple logistic regression analysis revealed that in the differentiation between frontotemporal dementia and Alzheimer's disease, the combination of Animal Fluency and Boston Naming Test correctly classified 90.5% of patients. In segregating semantic dementia and Alzheimer's disease, the combination of Boston Naming Test and Mini Mental State Examination resulted in a correct classification of 96.3%. These findings demonstrate that the Mini Mental State Examination and the language subtests of the CERAD-NAB are valuable clinical instruments for the differential diagnosis between early frontotemporal dementia, semantic dementia, and Alzheimer's disease.

Aged↗

Region-specific decline of cerebral glucose metabolism in patients with frontotemporal dementia: a prospective 18F-FDG-PET study.

OBJECTIVE: The aim of this study was to examine the pattern of glucose uptake and the changes over time of metabolic deficits in patients with frontotemporal dementia (FTD). METHODS: 10 patients who had received the clinical diagnosis of FTD underwent positron emission tomography scanning at the time of their first examination (baseline) and at follow-up (after 17.1 +/- 6.0 months). For statistical analysis, we used the SPM 99 software. First, we compared the data of the patients at baseline with an age-matched healthy control group. Second, we compared glucose uptake at follow-up with baseline measurements. RESULTS: Compared with normal controls, FTD patients showed significant metabolic deficits primarily in frontal cortical areas, but also in the caudate nuclei and the thalami. At follow-up, a significant progression of metabolic deficit was exclusively observed in the orbitofrontal parts of the frontal lobe and in the subcortical structures. DISCUSSION: These findings demonstrate that the clinical progression in patients with FTD is accompanied by a region-specific decline in cerebral glucose metabolism.

Brain Chemistry↗

[Mild cognitive disorder. Questions of definition, diagnosis, prognosis and therapy].

The syndrome of mild cognitive impairment (MCI) is heterogeneous in terms of aetiology, psychopathology, and prognosis. It is characterised by cognitive deterioration significantly exceeding the decline attributable to aging but not reaching the severity of dementia. The prevalence of MCI is estimated to be 17% in the population over 65 years old. At neuropathological examination, a large proportion of patients with mild cognitive impairment, particularly of the amnestic type, show typical features of Alzheimer's disease. The former progresses to dementia at an annual rate of 10% to 15%. In some cases, however, there is stable impairment or remission. The neurodegenerative process of Alzheimer's disease can be demonstrated in at least some patients using volumetric magnetic resonance imaging, 18-FDG positron emission tomography, or biochemical markers in the cerebrospinal fluid. It is not yet known whether patients with mild cognitive impairment or at least those with predementia Alzheimer's disease can benefit from currently available symptomatic treatments. Patients with early-stage Alzheimer's are an important target group for treatment interventions aiming at slowing the neurodegenerative process.

Adult↗

Cerebral metabolic patterns at early stages of frontotemporal dementia and semantic dementia. A PET study.

OBJECTIVE: To determine the patterns of cerebral glucose metabolism in frontotemporal dementia (FTD) and semantic dementia (SD). METHODS: 25 patients with mild FTD and 9 patients with mild SD as well as 15 healthy age-matched control subjects underwent 18F-FDG- positron emission tomography. Patient scans were compared with control scans using SPM-99. RESULTS: As compared with healthy control subjects patients with FTD showed an extensive symmetrical hypometabolism of the frontal lobes (height threshold P <0.01) which spared the motor cortex. Patients with SD showed a hypometabolism in the whole left temporal lobe and in the right temporal pole. CONCLUSIONS: In the clinical syndromes of FTD and SD two distinct patterns of cerebral metabolism were identified. FTD was associated with frontal hypometabolism, whereas in SD cerebral glucose metabolism was exclusively reduced in the temporal lobes. Our findings are consistent with the notion that FTD and SD begin as strictly lobar neuronal degenerations and that a spread of pathological changes is not seen until more advanced stages.

Aged↗

Lack of association between a single nucleotide polymorphism within the choline acetyltransferase gene and patients with Alzheimer's disease.

Alterations of the cholinergic system may account for typical clinical and pathophysiological disturbances of Alzheimer's disease (AD). In particular, a marked decline of choline acetyltransferase activity (CHAT) and as a consequence of acetylcholine during the course of the disease has been described. Due to the chromosomal localization of CHAT at 10q11.23 and its possible role in the pathophysiology of AD, CHAT may represent an appropriate candidate gene conferring risk to AD. In fact, a recent study identified a functional single nucleotide polymorphism (SNP) within the first common exon of CHAT, which was associated with AD giving an odds ratio of 3.8 (Neurosci. Lett. 333 (2002) 9). Because of the potential importance of this finding we analyzed this SNP and another functional SNP within exon 9 (rs868749) of the CHAT gene using a German case control sample consisting of 242 patients with AD and 143 cognitively healthy controls. No statistically significant differences were obtained for the previously described polymorphism. In addition, the exon 9 SNP (rs868749) was not polymorphic in the studied population. We conclude that the previously identified polymorphism is not associated with AD.

Aged↗

[Frontotemporal dementia. Results from "Frontotemporal Demential and Pick's Disease Conference"].

At the Frontotemporal Dementia and Pick's Disease Conference, recent data concerning the epidemiology, diagnosis, and therapy of frontotemporal dementia were presented. Topics included clinical manifestations, differential diagnosis, pathologic and genetic bases of the disease, therapy, and specific problems facing patients and care givers. A consensus in the terminology of this condition was sought.

Dementia↗

[Features of frontotemporal dementia from the perspective of a special family support group].

Eight spouses of patients diagnosed with frontotemporal dementia (FTD) participated in a special support group. Seven weekly sessions of 90-min duration were held. This pilot project provided the opportunity to learn more about FTD and the specific problems and needs of caregivers. Their problems are predominantly due to changes in the patients' personalities and behaviour, not to the cognitive impairment. Furthermore, in contrast to Alzheimer's disease, patients are relatively young, the current state of scientific knowledge about FTD is unsatisfactory, and the disease is almost unknown among physicians. As part of the group activity, caregivers received information on the typical symptoms of FTD. This enhanced their understanding of the alterations in the patients' personalities and behaviour and facilitated acceptance of the disease. During group meetings, participants were encouraged to express their own needs and to deal with painful emotions including aggression, anger, mourning, and guilt. The caregivers felt relieved by sharing their problems with others. They were able to learn from each other and to exchange suggestions and solutions. The group also helped to establish new contacts and friendships. Participants' evaluations of the novel intervention were very positive. We conclude from these initial observations that support groups are needed for caregivers of patients with FTD which are tailored to their specific needs.

Adaptation, Psychological↗

[German-speaking memory clinics: state of the art and practical recommendations].

The 7th annual meeting of the memory clinics of Germany, Switzerland and Austria in March 2002 in Göttingen, Germany was an optimal opportunity to make an inventory about the state of the art in diagnostic and therapy of dementia and mild cognitive impairment in German-speaking memory clinics. Several problems were discussed including difficulties in 1) diagnosis of patients with aphasia or foreign patients, 2) handling of demented patients without a caregiver, 3) psychological support for patients, who have been diagnosed in a very early stage, 4) misunderstandings between general practitioners, neurologists and psychiatrists in private practice on the one hand and the memory clinics on the other hand, 5) recommendations for prevention of dementia, 6) recommendations concerning dementia and car driving and 7) questions of genetic counselling. The following paper is a summary of the results of a workshop in Göttingen and gives practical recommendations based on the experiences of the memory clinics.

Aged↗

Tau and Abeta42 protein in CSF of patients with frontotemporal degeneration.

BACKGROUND: CSF concentrations of tau and beta-amyloid protein-42 (Abeta42) have been extensively studied in AD. Few data are available concerning CSF levels of both proteins in patients with frontotemporal degeneration (FTD). METHODS: The authors investigated CSF tau and Abeta42 concentrations in 34 patients with FTD, 74 patients with AD, and 40 cognitively healthy control subjects. CSF levels of tau and Abeta42 were measured by ELISA. With use of receiver operating characteristic-derived cutoff points and linear discrimination lines, the diagnostic sensitivity and specificity of both markers were determined. RESULTS: CSF tau concentrations were significantly higher in FTD than in control subjects but were significantly lower than in AD. CSF Abeta42 levels were significantly lower in FTD than in control subjects but were significantly higher than in AD. In subjects with FTD, neither tau nor Abeta42 levels correlated with the severity of dementia. The best discrimination between the diagnostic groups was obtained by simultaneous measurement of tau and Abeta42, yielding a sensitivity of 90% at a specificity of 77% (FTD vs controls) and a sensitivity of 85% at a specificity of 85% (FTD vs AD). CONCLUSIONS: In FTD, CSF levels of tau are elevated and Abeta42 levels are decreased. With use of these markers, subjects with FTD can be distinguished from control subjects and from patients with AD with reasonable accuracy.

Aged↗

Cerebrospinal fluid tau and beta-amyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment.

CONTEXT: Cerebrospinal fluid tau protein and beta-amyloid 42 (Abeta42) protein are altered even in very mild Alzheimer disease (AD). So far, few data exist for subjects with mild cognitive impairment (MCI). OBJECTIVE: To investigate the potential of cerebrospinal fluid tau and Abeta42 for predicting progression from MCI to AD in a longitudinal study of 28 patients with MCI who received follow-up for 18 months. DESIGN: An 18-month prospective study. SETTING: Clinical follow-up study of community-residing subjects with MCI. MAIN OUTCOME MEASURES: Cerebrospinal fluid tau and Abeta42 concentrations were measured using enzyme-linked immunosorbent assay at baseline. The potential of both biomarkers was evaluated to predict the progression to dementia, the end point of this study, using multiple logistic regression analysis. RESULTS: Of 28 subjects with MCI, 12 progressed to dementia (2 to frontotemporal dementia; 10 to AD). Six subjects had progressive MCI, and 10 subjects showed stable MCI. Cerebrospinal fluid tau levels were significantly elevated in patients who progressed to probable AD (P =.002) and subjects with progressive MCI (P =.003) compared with subjects who had stable MCI. Cerebrospinal fluid Abeta42 levels were significantly lower in patients who progressed to probable AD (P =.007) and those with progressive MCI (P =.04) than in subjects with stable MCI. Logistic regression analysis identified elevated tau protein level as a predictor of cognitive deterioration (P =.02), whereas a delayed verbal recall score at baseline was significantly associated with the development of probable AD (P =.03). CONCLUSION: Our results indicate that altered tau and Abeta42 concentrations may be detectable in subjects who are clinically diagnosed as having MCI but demonstrate the pathological changes of AD.

Aged↗

Frontotemporal dementia: patient characteristics, cognition, and behaviour.

OBJECTIVES: To describe sociodemographic data of patients with frontotemporal dementia (FTD), to compare the cognitive profile of patients with FTD with that of severity-matched patients with Alzheimer's disease using the CERAD neuropsychological battery (CERAD-NP), to investigate the frequency of behavioural disturbances, and to examine the relation between FTD-specific non-cognitive behavioural symptoms of patients with FTD with age and sex. METHODS: Fifty outpatients were diagnosed with FTD according to the Lund-Manchester consensus criteria. Cognitive impairment was assessed in 30 patients using the CERAD-NP. Severity of dementia was rated on the Clinical Dementia Rating (CDR). Eleven non-cognitive symptoms were rated by severity. To compare CERAD-NP results between patients with FTD and AD, 30 patients with AD were matched for age, sex, and global severity of cognitive performance. RESULTS: The average age at onset of first symptoms was 57.8 years. Eighteen patients (36%) had a positive family history of dementia. On the CERAD-NP patients with FTD performed significantly better than patients with AD on word list learning, delayed verbal recall and visuoconstruction (p < 0.05). There were no significant differences between FTD and AD on naming and verbal fluency tasks. The most frequent non-cognitive behavioural symptoms in FTD were loss of insight, speech abnormality, and apathy. Non-cognitive behavioural symptoms were more frequent in younger and in male than in older patients and in female patients. CONCLUSIONS: The CERAD-NP is a valuable clinical instrument for the cognitive evaluation of patients with suspected FTD. Complementary short tests of attention and executive function may be recommended. To enhance diagnostic sensitivity informant interviews should focus on non-cognitive behavioural changes, taking advantage of standardised questionnaires.

Adult↗

A polymorphism of the brain-derived neurotrophic factor (BDNF) is associated with Alzheimer's disease in patients lacking the Apolipoprotein E epsilon4 allele.

Because of its implication in neuroprotection, formation of long lasting memories and a disturbed function in Alzheimer's disease (AD), brain-derived neurotrophic factor (BDNF) may represent an appropriate candidate gene conferring risk to AD. Recently, a single nucleotide polymorphism (C-270T) within the BDNF gene has been associated with late onset AD in a Japanese population giving an odds ratio (OR) of 3.8. Because of the importance of this finding we analysed the BDNF polymorphism in a German sample consisting of 210 patients with AD and 188 cognitively healthy controls. The T-allele frequency was higher in patients with AD (11.9%) compared to controls (6.9%) (P = 0.035; OR = 2.26; 95% CI: 1.04-4.48). The risk conferred by the T-allele was stronger in patients who lack the ApoE epsilon4 allele giving an OR of 2.61 (1.21-5.64) P = 0.015, particularly in patients with early onset of the disease; OR 3.13 (1.32-7.43); P= 0.01. Due to the small number of patients showing both, lack of the ApoE epsilon4 allele and the BDNF T allele (n = 18), the result needs to be confirmed in a larger sample. The results suggest that the BDNF C-270T polymorphism is a relevant risk factor for AD particularly in patients lacking the ApoE epsilon4 allele in this German sample.

Age of Onset↗

Apolipoprotein E polymorphism in German patients with frontotemporal degeneration.

OBJECTIVES: The apolipoprotein E (apoE) polymorphism, designated as epsilon2, epsilon3, epsilon4, is a genetic risk factor associated with several forms of dementia. Inconclusive results have been reported in patients with frontotemporal degeneration which prompted this study of the apoE polymorphism in a German sample with frontotemporal degeneration. METHODS: the frequencies of the epsilon2 and epsilon4 alleles and the effect of these alleles on the age at onset in 52 patients with frontotemporal degeneration who underwent a thorough diagnostic examination and in 182 cognitively healthy age matched controls were assessed. Genotype comparisons between the groups were performed using multiple logistic regression analysis. Ages at onset according to the apoE genotype were compared by linear regression analysis. RESULTS: In patients with frontotemporal degeneration apoE epsilon2 and epsilon4 allele frequencies were 9.6% each, whereas the corresponding frequencies in controls were 9.6% and 9.9%, respectively. There was no significant difference in either epsilon2 or epsilon4 allele frequency between the groups. Age at onset was highest in patients with the epsilon2/epsilon3 genotype (61.3 years) followed by patients with the epsilon3/epsilon3 (58.3 years) and was lowest in patients with the epsilon3/epsilon4 genotype (56.4 years) but the differences failed to reach statistical significance. CONCLUSION: Allelic variants of the apoE gene do not modulate occurrence or age at onset in this sample of German patients with frontotemporal degeneration.

Age of Onset↗

Non-local concepts and models in biology.

In this paper, we consider local and non-local spatially explicit mathematical models for biological phenomena. We show that, when rate differences between fast and slow local dynamics are great enough, non-local models are adequate simplifications of local models. Non-local models thus avoid describing fast processes in mechanistic detail, instead describing the effects of fast processes on slower ones. As a consequence, non-local models are helpful to biologists because they describe biological systems on scales that are convenient to observation, data collection, and insight. We illustrate these arguments by comparing local and non-local models for the aggregation of hypothetical organisms, and we support theoretical ideas with concrete examples from cell biology and animal behavior.

Animal Communication↗

Gingival reaction on crowns with cast and sintered metal margins: a progressive report.

Sintered metals have been developed recently for the construction of metal ceramic crowns (Degusint U). An unbalanced, randomized double-blind study was conducted to compare the gingival response to artificial crowns with sintered noble metal margins and cast noble metal margins (Degudent U) by measuring the sulcus-fluid-flow rate (SFFR) in highly motivated patients. In a prior study marginal opening of 20 microns were recorded for cast metal crowns, whereas two sintered metal crowns had marginal openings of 40 microns. Three metal ceramic crowns (Renaissance, Degusint U, and Degudent U for the copings and VMK 68 porcelain) with subgingival margins were prepared and fabricated for 12 intact natural teeth. The SFFR was measured for teeth with artificial crowns and adjacent natural teeth after provisional insertion of each crown. Significantly elevated SFFRs were recorded for all artificial crowns compared with the adjacent natural teeth, but there were no variations recorded for the different types of crown margins.

Analysis of Variance↗