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H Förstl

Publications and source records attributed to H Förstl.

At least 19 recordsLinked to original sources
PubMed2006

Fine mapping of the MAPT locus using quantitative trait analysis identifies possible causal variants in Alzheimer's disease.

In addition to senile plaques, neurofibrillary tangles are characteristic of Alzheimer's disease (AD) pathology, suggesting a clear involvement of the microtubule-associated protein tau (MAPT) in AD. Recent findings, suggesting that the H1c haplotype is associated with increased risk, now also implicate MAPT genetically. In this study, we aim to clarify this association by a fine mapping approach using both a traditional phenotypic association analysis and a quantitative trait (QT) analysis using cerebrospinal fluid (CSF) tau protein levels in the German population. Here, we report that both methodologies identify that the H1c haplotype may play important role in AD (AD risk, P=0.007, uncorrected; CSF tau levels, P=0.027, uncorrected). Further, the use of a sliding window approach in the QT analysis allowed for the narrowing down of the region where a probable causal variant may be located. The data suggest that this may lie at or within close proximity to the rs242557 single nucleotide polymorphism as association with CSF tau levels seems to be primarily driven by rs242557 in a gene dosage-dependent manner (trend model: P=0.002, uncorrected). These findings provide functional evidence to support the genetic association of MAPT with AD.

Aged↗
PubMed2006

[Initial symptoms, survival and causes of death in 115 patients with frontotemporal lobar degeneration].

The early and differential diagnosis of the clinical phenotypes of frontotemporal lobar degeneration (FTLD), including frontotemporal dementia (FTD), semantic dementia (SD) and non-fluent progressive aphasia (NFPA), can be challenging. It may be difficult not only to differentiate these conditions from normal aging, psychiatric disorders, and other dementias, but also to distinguish between them. For early diagnosis, information on the initial and presenting symptoms of the FTLD phenotypes is essential. In the present study caregivers of 78 patients with FTD, 20 patients with SD and 17 patients with PA were interviewed about initial symptoms. In patients with FTD, the most frequent initial symptoms were alterations of personality, followed by forgetfulness and word finding difficulty. Patients with SD presented with word finding difficulty and behavioral disturbances. Almost all patients with PA developed word finding difficulty as the first manifestation of their disorder. Diagnostic latency - the time from disease onset to diagnosis was 4.1 years in FTD, 4.2 years in SD and 3.1 years in PA. Caregivers, and in some cases also patients, should be educated about the likely course and mortality of FTLD. To obtain information about survival time and cause of death associated with FTLD we analyzed follow-up data on 106 patients of whom 25 had died. The median survival time from the occurrence of first symptoms was 14 years. Mortality risk was significantly higher in patients with an early disease onset. Causes of death were varied, but pneumonia and sudden unexplained deaths were particularly frequent.

Age of Onset↗
PubMed2006

Behavioral disturbances in the course of frontotemporal dementia.

BACKGROUND: Behavioral disturbances are prominent in frontotemporal dementia (FTD), and their occurrence has been the topic of several investigations. Nonetheless, the prevalence and severity of behavioral disturbances of patients with FTD in different degrees of dementia severity have rarely been studied. OBJECTIVE: The aim of this study was to assess and compare the prevalence and severity of behavioral disturbances in patients with mild FTD and in patients with moderate/severe dementia. METHODS: We included 21 outpatients with mild FTD [Clinical Dementia Rating (CDR) = 1] and 19 patients with moderate or severe dementia (CDR = 2 or 3) in this study. Behavioral disturbances were assessed using the Neuropsychiatric Inventory (NPI). RESULTS: We found a statistically significant difference in the total NPI scores between patients with mild FTD and patients with moderate or severe FTD, the latter scoring higher. Apathy was the most prevalent symptom in both patient groups (90.5 and 100%). Except appetite and eating disturbance, which appeared in 77.8% of the patients with moderate/severe dementia, all other symptoms were clearly less common (<50%). CONCLUSION: The results highlight the variability of behavioral disturbances in mild and moderate/severe stages of FTD.

Age of Onset↗
PubMed2006

No association of vacuolar protein sorting 26 polymorphisms with Alzheimer's disease.

Using a case-control sample we evaluated a possible involvement of the Vacuolar protein sorting 26 (VPS26) gene in the pathogenesis of AD. VPS26 located at 10q22.1 denotes a retromer subunit functionally involved in the cellular trafficking of Memapsin 2 (BACE). Genotyping of eight single nucleotide polymorphisms covering the complete VPS26 gene and haplotypic analysis revealed no association with AD. Thus, we conclude that VPS26 can be excluded as a major positional and functional candidate gene conferring risk to AD.

Aged↗
PubMed2006

Decline of cerebral glucose metabolism in frontotemporal dementia: a longitudinal 18F-FDG-PET-study.

OBJECTIVE: To identify the pattern of progression of decline of cerebral glucose metabolism in frontotemporal dementia (FTD, frontal variant). METHODS: 22 patients with mild FTD underwent 18F-FDG-positron emission tomography at baseline and at follow-up in average 19.5 months later. Patient scans were compared with scans from 15 healthy age-matched control subjects on a voxel-by-voxel basis using SPM-99. RESULTS: As compared with healthy control subjects at baseline patients with FTD showed a significant symmetrical hypometabolism of the frontal lobes sparing the motor cortex, of the caudate nuclei, insula and thalamus bilaterally. At follow-up further significant reductions in glucose metabolism were observed in the parietal and temporal cortices. CONCLUSIONS: In early stages of FTD the neurodegenerative process is limited to the frontal lobes. During the progression of the disease, the pathological changes pass over the lobar borders and spread into the parietal and temporal cortices.

Aging↗
PubMed2006

[Presenile dementia in memory clinics--incidence rates and clinical features].

This study describes the clinical features of presenile dementia diagnosed in memory clinics. It further gives an estimate of the declared incidence for the German city of Munich and surrounding counties. Twelve memory clinics in Switzerland and Germany were considered, among them all of the four in Munich. A total of 267 patients with onset of illness under the age of 65 were included. Only 16 patients (6%) were younger than 50. Men and women were affected about equally often. The most common cause of dementia was Alzheimer's disease (67%), followed by frontotemporal degeneration (13.5%) and vascular (5.6%) dementia. The declared incidence was estimated at 8.3 new cases of dementia per year among 100,000 persons in the 50-64 age range, with an incidence rate of Alzheimer's disease at 6.3/100,000. It can be concluded that memory clinics fulfill an important function in the care of patients with presenile dementia, since they are highly utilized by younger patients in early stages of the illness.

Adult↗
PubMed2006

[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↗
PubMed2005

[Relationships between mental and cardiac diseases].

Affective and schizophrenic illnesses are associated with an elevated--in particular cardiovascular-related--risk of mortality. Patients with a cardiac disease who suffer from episodes of depression should be treated with selective serotonin reuptake inhibitors. Sertraline and citalopram have a low potential for interaction. Thioridazine, pimozid and ziprasidone are the substances that most commonly lead to lengthening of the QTc interval and thus to repolarization disorders. However, the results of studies carried out to date show that, in contrast to thioridazine and pimozid, ziprasidone has not so far been suspected of having an association with sudden heart death. Prior to starting treatment with tricyclic antidepressants or neuroleptics, a baseline ECG should be obtained. Follow-up ECG should be recorded and consideration given to possible drug interactions leading to cardiac arrhythmias, in particular when low-potency antipsychotics are used.

Controlled Clinical Trials as Topic↗
PubMed2005

The Alzheimer variant of lewy body disease: a pathologically confirmed case-control study.

The objective of the study was to identify clinical features that distinguish patients with dementia with Lewy bodies (DLB), who were classified as Alzheimer's disease (AD) patients, from patients with AD. We examined a group of 27 patients from our memory clinic, originally diagnosed with AD, of whom 6 were postmortem found to have DLB. For the present study, we compared cognitive, noncognitive and neurological symptoms between the two groups. We found that there were no differences on ratings of dementia and scales for activities of daily living. Patients with DLB performed better on the MMSE and the memory subtest of the CAMCOG, but there was no difference in any other cognitive domain. Furthermore, genetic risk factors, including family history of dementia or allele frequency of the apolipoprotein epsilon4, did not discriminate between the two groups, and there were no differences on CCT scans. Taken together, our findings suggest that Lewy body pathology may be present in patients who do not show the typical clinical features which distinguish DLB from AD.

Aged↗
PubMed2005

[Nightmares in patients with Alzheimer's disease caused by donepezil. Therapeutic effect depends on the time of intake].

Dementia of the Alzheimer type (DAT) has been linked to losses of cholinergic function in the brain. The acetylcholinesterase inhibitors donepezil, rivastigmine and galantamine improve cognitive performance in manifest dementia. These substances, however, also influence the quality of sleep, and particularly the quality and amount of dreams. We therefore investigated the influence of the time point of donepezil intake on the occurrence of nightmares. We observed a clear-cut relationship between the occurrence of nightmares and an evening dose of donepezil in eight patients with DAT. None of these patients reported nightmares when donepezil was taken in the morning. We suggest that the activation of the visual association cortex during REM sleep is enhanced by donepezil, a mechanism most likely facilitating the development of nightmares in patients with DAT.

Aged↗
PubMed2005

Postoperative acute confusional state in typical urologic population: incidence, risk factors, and strategies for prevention.

OBJECTIVES: To determine the incidence of, and predictors for, the acute confusional state (ACS) in older patients after urologic surgery. ACS is among the most common complications after surgery in older patients. It is associated with increased postoperative morbidity, longer hospital stays, and greater mortality. Agitation caused by ACS might have deleterious consequences in a large proportion of older patients, especially after urologic surgery. Only a few studies, of highly selected urologic procedures, have been reported, and all showed an astonishingly low percentage of patients with this distressing condition. METHODS: We examined 100 consecutive, older patients (age 60 years or older), prospectively, before and after urologic surgery, to determine both the incidence of, and the predictors for, ACS. RESULTS: Only 7 of the 100 patients developed postoperative ACS. The risk factors identified were preoperative cognitive deficits, pre-existing depression, impaired vision, and the operative time. CONCLUSIONS: These results suggest that postoperative ACS is relatively rare after urologic surgical procedures; however, patients who are likely to develop ACS can be identified, prompting consideration for prophylactic antidelirium care.

Acute Disease↗
PubMed2005

[Heart and brain -- the influence of psychiatric disorders and their therapy on the heart rate variability].

Psychiatric disorders are associated with autonomic dys-regulations. There is evidence that these dys-regulations are partly responsible for the increased mortality in patients with psychiatric disorders. The determination of the heart rate variability (HRV) is a method easily applicable and allows the assessment of the autonomic control of the heart rate regulation. A multitude of HRV parameters with different physiological meanings have been introduced, the most widely used parameters are presented and characterized in this paper. Many studies have shown a reduced HRV in patients with major depression. Most studies found a reduced parasympathetic activity. However some authors discuss an elevated sympathetic activity. The magnitude of HRV reduction correlates to the severity of the depression. In patients with coronary diseases, major depression is an independent risk factor of mortality. Antidepressive therapy with serotonin reuptake inhibitors has failed to improve the prognosis of this patients. Patients with panic disorders also have a reduced HRV due to an elevated sympathetic control and reduced vagal control. In schizophrenic patients a reduced HRV was found in long term electrocardiogram recordings, whereas short term recordings did not show a reduced HRV. Patients with Alzheimer's disease also have a reduced HRV, which is limited to the low frequency component. Therapy with cholinesterase inhibitors further influences HRV by reducing the high frequency component and might increase the risk for arrhythmias. HRV analysis and integration in the assessment and monitoring of psychiatric patients before and during therapy elucidate the role of autonomic disturbances in such diseases and may help to optimize treatment.

Alzheimer Disease↗
PubMed2005

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↗
PubMed2005

Neurological soft signs are associated with APOE genotype, age and cognitive performance.

Neurodegeneration is associated with increased frequency of neurological soft signs (NSS). We designed the present study to investigate the association between NSS and subjective memory complaints, cognitive function and apolipoprotein E genotype in a community-dwelling sample of volunteers participating in an ongoing longitudinal program investigating predictors of cognitive decline. NSS were found to be associated with apolipoprotein E (APOE) epsilon4 genotype (p = 0.015), age (p = 0.012) and poor cognitive performance, as assessed by the Mini Mental State Examination (p = 0.053). There was no significant difference between subjects with and without memory complaints in relation to the frequency of NSS (p = 0.130). The association with age and the APOE epsilon4 genotype suggests that the systematic investigation of NSS may contribute to identify subjects at risk of clinically significant cognitive decline in later life.

Adult↗
PubMed2004

Prion protein codon 129 polymorphism and risk of Alzheimer disease.

The authors investigated the PRNP Met129Val polymorphism in 1,393 subjects including 482 patients with Alzheimer disease (AD) and two independent control groups. In patients, PRNP Met homozygosity conferred increasing risk with decreasing age at onset (onset: 61 to 70 years, n = 151, p = 0.02, odds ratio [OR] = 1.72, 95% CI = 1.2 to 2.53; onset: < or =60 years, n = 138, p = 0.013, OR = 1.92, 95% CI = 1.31 to 2.87), whereas no association was obtained in patients with onset at older than 70 years. The results suggest involvement of the prion protein in the pathogenesis of early-onset AD.

Age of Onset↗
PubMed2004

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↗
PubMed2004

[Frontotemporal dementia: specific problems for caregivers].

Frontotemporal dementia is a relatively rare neurodegenerative disease. In the majority of cases the onset is at a presenile age, and changes of behavior as well as alterations of personality and social conduct are predominant symptoms whereas cognitive deficits are mild. Therefore interventions for caregivers including self-help groups and educational programs which are usually tailored to Alzheimer's disease often do not meet the needs of caregivers of patients with FTD. The present paper reviews the clinical features of FTD, outlines the specific problems and burdens that caregivers are faced with, and describes novel interventions for this group of family caregivers.

Age Factors↗