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Hans Förstl

Publications and source records attributed to Hans Förstl.

At least 19 recordsLinked to original sources
PubMed2007

Personality change in old age.

PURPOSE OF REVIEW: The present short review summarizes some of the most important personality changes in older adults. RECENT FINDINGS: Personality changes in old age are usually minimal. Cluster B personality disorders appear to become less prevalent. Significant changes in personality are typically associated with frontotemporal lobar degeneration (e.g., slowly progressive sociopathy), Alzheimer's disease, mild cognitive impairment due to incipient dementia or underlying medical illness. SUMMARY: Therefore, we suggest that a significant change in personality in old age always warrants careful neuropsychiatric examination.

Adaptation, Psychological↗
PubMed2006

No association of chromatin-modifying protein 2B with sporadic frontotemporal dementia.

Mutations of the chromatin modifying protein 2B gene (CHMP2B) were identified, in a Danish pedigree, to cause familial frontotemporal dementia (FTD). To explore the possible genetic contribution of common CHMP2B variants in sporadic FTD, we analyzed 14 single nucleotide polymorphisms covering the entire genomic region of CHMP2B. After adjustment for multiple testing single marker and haplotype analysis revealed no significant association with sporadic FTD. Thus, we conclude that CHMP2B can be excluded as a susceptibility gene conferring risk to sporadic forms of FTD.

Aged↗
PubMed2006

A functional polymorphism within plasminogen activator urokinase (PLAU) is associated with Alzheimer's disease.

A number of susceptibility loci for Alzheimer's disease (AD) have been identified including a region on Chromosome 10q21-q22. Within this region the plasminogen activator urokinase gene (PLAU) was considered as a reasonable candidate from its functional implication in plasmin generation, a serine protease capable of degrading beta-Amyloid (Abeta) protein. We screened 56 single nucleotide polymorphisms (SNPs) around PLAU using 1751 individuals from four independent case-control samples (Munich, N=679; Bonn N=282; Brescia (Italy) N=219; Perth (Australia) N=557 and one discordant sib-pair sample (Munich N=622). In brain tissue samples of neuropathologically confirmed cases with AD (N=33) we analyzed plaque counts according to the risk allele. We identified that one functional exonic SNP (rs2227564) is associated with development of AD using the four independent case-control samples (Munich, P=0.02; Bonn, P=0.005; Brescia (Italy), P=0.001; Perth (Australia), P=0.03) and the discordant sib-pair sample (P=0.001). In brain tissue, from neuropathologically confirmed cases with AD, we identified significantly higher plaque counts in carriers of the risk allele (N=6; 60.3+/-16.9) compared with non-carriers (N=9; 26.3+/-8.8; P=0.007). This study provides compelling evidence of a genetic and functional involvement of a common PLAU variant into the pathogenesis of AD. Further functional investigations are warranted to elucidate the specific role of PLAU, respectively, PLAU variants in the metabolism of Abeta proteins.

Age of Onset↗
PubMed2006

Weak independent association signals between IDE polymorphisms, Alzheimer's disease and cognitive measures.

Functional and genetic studies suggest that insulin-degrading enzyme (IDE) may be a strong functional and positional candidate. As there is a lack of consensus in regards to the level and location of IDE association signals we aimed to clarify these discrepancies through genotyping 28 SNPs in a large case-control collective together with quantitative measures of cognitive ability (MMSE). Four SNPs (rs11187007, rs2149632_ide12, rs11187033, rs11187040) were found to be associated with AD (nominal p<0.01). Tests with MMSE scores adjusted for disease duration identified associations, with the most significant result for rs1999763 (nominal p=0.008). Similarly, different reconstructed IDE haplotypes were associated with AD and higher MMSE scores. The association signals are only borderline significant after adjustment for multiple testing, but add further evidence to previous published results on the association between IDE and AD or MMSE. A subgroup analysis indicated more prominent associations with AD in younger, and with MMSE in older patients. There may be two independent effects mediated by IDE variants, risk for AD and modification of disease progression.

Aged↗
PubMed2006

Dementia in the Greco-Roman world.

Greek and Roman physicians developed distinct and detailed ideas, which can be regarded as early versions of our modern concept of dementia. Several classical sources--some of them medical--offer intriguing descriptions of many cognitive and behavioral symptoms in dementia, which are currently used for diagnostic purposes. Limitations of this ancient concept are due to terminological and epidemiological factors, but also to the physicians' social role. Only a small part of this early literature is cited in contemporary work on the origin of the dementia concept, which can be clearly traced back to the Age of Enlightenment and whose earlier history still needs to be elucidated.

Aging↗
PubMed2006

The cathepsin D rs17571 polymorphism: effects on CSF tau concentrations in Alzheimer disease.

The lysosomal protease cathepsin D (CtsD, EC 3.4.23.5; gene, CTSD) has been associated with Alzheimer disease (AD) due to its cerebral expression being increased early in the course of AD; additionally, a CTSD exon 2 polymorphism (rs17571; NT_009237.17:g.569834T>C) may confer risk to AD. Functionally, it may be implicated in amyloid precursor protein (APP) processing and tau protein degradation. The objective of this study was to determine whether the CTSD exon 2 polymorphism affects cerebrospinal fluid (CSF), concentrations of beta-amyloid (Abeta42) and tau in two independent samples from Germany (n=73) and Sweden (n=66). Patients carrying the CTSD rs17571-T allele had significantly decreased CSF levels of tau (Munich, p=0.003; Swedish, p=0.029; combined sample, p<0.001), whereas no significant effect was observed on Abeta42 concentrations. Likewise, no significant impact was observed on Mini Mental State Examination (MMSE) scores. The data of both independent samples suggest that the CTSD rs17571 polymorphism does not affect APP processing but shows significant effects on tau processing. The result may corroborate the implication of the lysosomal system in the pathogenesis of AD and is of particular importance if CSF tau is used as a diagnostic biomarker.

Alzheimer Disease↗
PubMed2006

New aspects of psychiatric morbidity in idiopathic environmental intolerances.

OBJECTIVE: To understand idiopathic environmental intolerances (IEI)-formerly multiple chemical sensitivities (MCS)-it is helpful to outline its characteristic psychiatric morbidity. METHOD: We applied a standardized interview according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (SCID) to 305 environmental patients with and without IEI. RESULTS: Somatoform, affective and anxiety disorders were the most frequent diagnoses but only slightly differed between patients with or without IEI. In both groups, current substance-related disorders were rare. We found a clearly higher prevalence of psychotic, especially current delusional disorders, in IEI. CONCLUSION: Somatization, depression, and anxiety are frequent in IEI but nonspecific. Psychotic disorders are more common in IEI than in other types of environmental illness. It appears worthwhile to study personality and cognitive style to explain the pivotal features of IEI.

Adolescent↗
PubMed2005

TNF polymorphisms in Alzheimer disease and functional implications on CSF beta-amyloid levels.

Alzheimer disease (AD), vascular dementia, and stroke are all associated with inflammation though their respective initiating factors differ. Recently a polymorphism in the proinflammatory cytokine tumor necrosis factor (TNF), in association with apolipoprotein E (APOE), was reported to increase AD risk. Two SNPs, rs1799724 (-850C>T; NT_007592.14:g.22400733C>T) and rs1800629 (-308G>A; [NT_007592.14:g.22401282G>A]), and the APOE polymorphism were genotyped in 506 patients with sporadic AD and in 277 cognitively healthy controls. In a subset of 90 individuals we also investigated whether these SNPs exerted any functional effects on cerebrospinal fluid (CSF) beta-amyloid (Abeta) levels. The frequency of the rs1799724 genotypes and the rs1799724-T allele were significantly different in AD individuals (P=0.009; odds ratio [OR], 1.63; 95% confidence interval [CI], 1.13-2.34), while the rs1800629 SNP was not associated with AD. Significant interaction was observed between the rs1799724-T and APOE epsilon4 alleles in that the rs1799724-T allele significantly modified risk associated with possession of the epsilon4 allele only (epsilon4 in absence of rs1799724-T: OR, 2.92; 95% CI, 2.00-4.27; epsilon4 in presence of rs1799724-T: OR, 6.65; 95% CI, 3.26-13.55; P=0.03). Haplotyping analysis revealed a significant overrepresentation of an rs1799724-T/rs1800629-G haplotype in AD (P=0.012; OR, 1.60; 95% CI, 1.11-2.29), although to a lesser degree than rs1799724-T alone. Further, the rs1799724-T allele was found to be associated with lower levels of CSF Abeta42 (P=0.023), thus corroborating the genetic findings. Inheritance of the rs1799724-T allele appears to synergistically increase the risk of AD in APOEepsilon4 carriers and is associated with altered CSF Abeta42 levels. Further investigations are warranted to assess the significance of these novel findings.

Aged↗
PubMed2005

Self-reported chemical sensitivity in Germany: a population-based survey.

OBJECTIVES: Environmental clinics are frequented by patients with fears and complaints related to environmental triggers. A dose-independent overreaction to small doses of widely used and generally non-toxic chemicals is referred to as multiple chemical sensitivity (MCS), but no clearly defined clinical syndrome with objective physical findings has been delineated so far. We aimed to obtain information about symptoms, supposed environmental triggers, the frequency of self-reported chemical sensitivity, and of the diagnosis MCS in Germany. METHODS: We conducted a representative survey among 2032 adult Germans. RESULTS: We found self-reported chemical sensitivity in 9% and physician-diagnosed MCS in 0.5% of our representative sample. Physical complaints were common in the whole study population and in chemically sensitive individuals, but there was no clear-cut symptom constellation among the latter. The most common complaints were headache, fatigue, sleep disturbances, joint pain, mood changes and nervousness. A subjective connection between complaints and environmental triggers was denied by 67% of the whole group and by 35% of the self-reported chemically sensitive. Factor analysis of environmental triggers suggested that a specific exposure situation rather than chemical similarity is the basis for individual trigger combinations. CONCLUSIONS: The prevalence of subjective sensitivity towards chemicals is similar to such rates reported from other countries. There is a relatively low awareness of the MCS-concept, and it appears to be diagnosed less frequently than, e.g., in the USA. Since symptoms and triggers in chemically sensitive individuals did not differ from the general population, our data do not suggest the existence of a widespread new syndrome related to chemical sensitivities in Germany. We outline the limitations of self-reported chemical sensitivity as the major criterion for such a contentious diagnosis as MCS.

Adolescent↗
PubMed2005

Uncommon causes of dementia: an historical account.

The search for the possible causes of common and uncommon forms of dementia has a long and interesting history. This paper presents a brief review of how the concept of dementia has evolved over time and an historical outline of the causative factors associated with these disorders. Currently available evidence leads to the conclusion that there is only one common cause of dementia: Alzheimer's disease with or without other overlapping pathological processes (such as cerebrovascular disease, traumatic brain injury, etc.). All other forms of dementia are, in isolation, uncommon.

Cerebrovascular Circulation↗
PubMed2005

'Alzheimer's disease': more data, but are we any more informed?

PURPOSE OF REVIEW: While we adhere to traditional misconceptions regarding the nature of age-associated neurodegenerative, and vascular and other brain changes, we will not re-design our research projects, and we will not reconsider and improve our pragmatic diagnostic and therapeutic approach. RECENT FINDINGS: This review focuses (1) on the continuum of cognitive deficits from mild cognitive impairment to manifest dementia, (2) on the spectrum of neurodegenerative, vascular and other cerebral co-morbidity, and (3) on some reversible examples of the rare outliers (limbic encephalitis, Hashimoto encephalopathy) not to be included in the common severity and cerebral co-morbidity spectrum of senile cognitive impairment. SUMMARY: We will only be more informed if we accept appropriate concepts and draw the right conclusions. Important new research has not yet filtered into the minds of dementia researchers specializing in 'normal ageing' or 'mild cognitive impairment', 'Alzheimer's disease' or 'dementia with Lewy bodies', tauopathies or synucleopathies, etc.

Journal Article↗
PubMed2004

[Incidence and risk factors of delirium after hip surgery].

OBJECTIVE: Postoperative delirium is common among elderly hip surgery patients. The objective of the current study was to determine the incidence of delirious states and to identify possible risk factors. METHOD: The sample consisted of 200 consecutive patients, age 60 years and older, who underwent hip surgery because of acute hip fracture or elective hip replacement. Patients were prospectively assessed preoperatively and on a daily basis postoperatively using the Confusion Assessment Method (CAM). Associations between risk factors and delirium were analysed by means of multiple logistic regression models. RESULTS: 20.5 % of the sample were diagnosed with postoperative delirium. Statistically significant risk factors for the development of delirium were higher age, lower preoperative cognitive test performance and severe physical comorbidity. Some other putative risk factors tended to be associated with postoperative delirium, but failed to reach statistical significance. CONCLUSIONS: The study confirmed a high incidence of delirium among hip surgery patients. Apart from established risk factors like old age, low cognitive test performance, and comorbidity, no other significant risk factors could be identified.

Aged↗
PubMed2003

Mild cognitive impairment: making headway by stepping backwards.

Mild cognitive impairment (MCI) is a prevalent medical problem and the concept and term have become a catch-phrase for research and clinical practice. However, little is known about the most effective tools for a clinical diagnosis of MCI, its potential significance for individual patients and the best possible intervention--at least as long as MCI is considered as a diagnostic entity. We propose a simplified diagnostic and interventional algorithm for the detection and management of patients with MCI. We argue that MCI is so important, because it represents the closest call for an identification of treatable diseases or risk factors before the final manifestation of irreversible brain changes. Stepping backward by focussing on underlying disease processes and attempting causal interventions must be preferred to a mere symptomatic treatment of MCI as a preclinical form of Alzheimer's disease.

Age of Onset↗
PubMed2003

Alzheimer-plus.

Explore the source record for details and available documents.

Aged↗
PubMed2002

The clock drawing test and questionable dementia: reliability and validity.

OBJECTIVES: In order to evaluate the suitability of the clock drawing test (CDT) for the detection of questionable dementia (QD), we assessed the inter-rater reliabilities and intercorrelations of four common scoring methods of the CDT in a sample of non-demented subjects and determined the concurrent validity. METHODS: The study sample consisted of 253 discharged general hospital patients, aged between 65 and 85 years. Subjects were screened for cognitive impairment during their hospital stay. Four to six weeks after discharge each non-demented patient was visited at home and interviewed by a trained psychologist. The interview procedure included a cognitive test battery incorporating the CDT, the Mini-Mental State Examination (MMSE), the Syndrome Short Test (SKT), and a verbal fluency test (VF). The criteria of the Clinical Dementia Rating (CDR) were used to differentiate between cognitively normal subjects and those with QD. Clock drawings were scored independently and blindly by two raters according to four different methods. The agreement between raters was assessed, as well as the agreement between the different scoring methods. The association of gender, education, age, test performance and CDR-rating with CDT scores was examined. Accuracy of the CDT for the detection of QD was calculated. RESULTS: Inter-rater reliabilities were high for all four scoring methods. However, substantial differences among the scoring methods were observed, the proportion of abnormal test results varying between 9% and 50%. The CDT correlated significantly with MMSE, SKT and VF, but correlation coefficients were low (r = 0.13 to r = 0.32). Furthermore, CDT scores were influenced by age, gender, and education. Sensitivity of the CDT for QD was 66%, specificity was 65%; the negative predictive value was 73%, the positive predictive value 58%. CONCLUSION: In a sample of non-demented elderly, the reliability of the CDT was sufficiently high, but the different scoring methods were not equivalent. When established cut-off scores were used, the proportion of abnormal CDTs were significantly different. Concurrent validity with other common cognitive tests was unsatisfactory. The CDT lacks sufficient sensitivity and specificity for the identification of QD and should not be used alone to screen for possible prodromal stages of dementing illnesses. The association of age, gender and level of education with CDT scores should be taken into account by clinicians using the CDT.

Aged↗
PubMed2002

[Increased level of tonic sympathetic arousal in high-vs. low-alexithymic cervical dystonia patients].

The purpose of this study was to assess whether alexithymia is a risk factor for autonomic dysregulation in cervical dystonia (spasmodic torticollis, ST). Alexithymia was assessed by an authorized German version of the TAS-20. In a first step, we recruited 10 ST-patients with high alexithymia scores (> 62; M = 69.2, SD = 3.0) and compared them with 10 ST-patients with low alexithymia scores (< 35; M = 28.7, SD = 4.3) on physiological and subjective responses to a cognitive and an emotional laboratory stressor. High-alexithymic ST-patients generally showed increased levels of autonomic arousal (higher SCL, more NS.SCF and lower T; 0.016 </= p </= 0.065) under all experimental conditions. In a second step, we used a less extreme alexithymia-definition (high >/= 57 vs. low </= 36) in a sample of 2 x 20 probands and found no significant differences. Our results suggest a chronically increased level of sympathetic activation in high-alexithymic patients with spasmodic torticollis.

Adult↗
PubMedDate not supplied

Association between the presenilin-1 mutation Glu318Gly and complaints of memory impairment.

Presenilin-1 mutations account for nearly 50% of all early-onset familial cases of Alzheimer's disease. Most of these mutations are completely penetrant, although the recently described Glu318Gly substitution seems to have only partial penetrance. These findings suggest that the Glu318Gly mutation may work as a genetic risk factor for Alzheimer's disease. We designed the present study to investigate the frequency of this mutation among non-demented volunteers with subjective memory impairment (n = 58) and controls (n = 66). Four (6.8%) subjects with complaints of memory problems, but no controls, carried this mutation. The presence of the Glu318Gly mutation was associated with significantly lower cognitive performance when compared to controls (P = 0.011). However, there was no significant association between the presence of the mutation and the cognitive performance of individuals within the memory complainers group. Follow-up studies should clarify whether the Glu318Gly mutation increases the risk of cognitive decline in later life.

Adult↗