Tracking of Alzheimer's disease progression with cerebrospinal fluid tau protein phosphorylated at threonine 231.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
H Hampel
Publications and source records attributed to H Hampel.
Polymorphisms in the alpha-2 macroglobulin gene in psychogeriatric patients.
Recent reports have suggested that genetic polymorphisms in the alpha-2 macroglobulin (A2M) gene are associated with an increased risk for Alzheimer's disease. In the present study we tested two polymorphisms in the alpha-2 macroglobulin gene, a 5 bp deletion at the 5' splice site of exon 18 and a G/A point mutation (V1000I) in exon 24, in a sample of 118 healthy, non demented controls and 238 consecutively recruited gerontopsychiatric patients, diagnosed as: Alzheimer's disease (N=88), mild cognitive impairment (N=32), subjective cognitive complaints (N=54) and depression/other psychiatric disorders (N=64). The aim of this study was to test whether the investigated polymorphisms has a high enough selectivity and specificity to distinguish between the different gerontopsychiatric disorders or to differentiate genetically AD from other forms of dementia, respectively. Also a possible relation to the APOE varepsilon4 polymorphism was examined. Our study failed to show an association between the two investigated polymorphisms in the alpha-2 macroglobulin gene and any of the four different psychogeriatric patient subgroups, either alone or in combination with the APOE varepsilon4 genotype.
Aged↗
[Your help is needed! Autopsy brings new knowledge regarding Alzheimer dementia].
Diagnosis upon autopsy of patients suffering from Alzheimer's disease (AD) and other dementing disorders is required to confirm or reject the clinical diagnosis. Autopsy studies are crucial to validate diagnostic criteria as well as to gain new insights in AD epidemiology, genetics, pathophysiology and therapy. The current decrease of autopsy rates leads to a lack of research which is essential to improve diagnosis and therapy of AD. Only the cooperation between physicians in memory-clinics, general practitioners and neuropathologists can prevent this unfortunate development. Brain-Net, the German brain bank, is a unique approach to provide organisational support for such a concerted action.
Aged↗
Detection of tau phosphorylated at threonine 231 in cerebrospinal fluid of Alzheimer's disease patients.
A new sandwich ELISA is described which shows specificity for tau phosphorylated at threonine 231 and preferentially reacts with Alzheimer's disease (AD) brain extracts relative to other dementias. This assay was used to analyze 58 antemortem cerebrospinal fluid samples. Twenty-three of 27 AD samples (85% sensitivity) yielded signals greater than the cutoff, while only one of 31 non-AD samples (97% specificity) were greater. This indicates that detection of phosphotau in cerebrospinal fluid with this sandwich ELISA could prove useful in the diagnosis of AD.
Aged↗
[Therapy of Alzheimer dementia. Current status and prospects].
In recent years, considerable progress has been made both in the diagnosis and treatment of dementia. Drugs have been developed which enhance cognitive performance in a large percentage of those afflicted, delay impairment of the ability to cope with the tasks of daily life, and avoid premature admission to a nursing home. In the practical medical care setting, however, these advantages are being utilized to only a limited extent, and this despite the fact that numerous therapeutic options are now available for the treatment of AD. New therapeutic approaches are aimed at inhibiting the pathological cleavage and extracellular and intracellular deposition of amyloid, preventing the toxic effects of amyloid accumulation around the neurons, and re-establishing intracellular transport deranged by the aggregation of neurofibrils. A further approach is the use of combinations of available substances with differing, possibly synergic, effects. Over and beyond this, treatment of AD in the "presymptomatic stage", or in the stage of only mild cognitive disturbance, is currently the subject of clinical trials.
Aged↗
[Old myths hinder therapy. Memory disorders are not an expression of "normal" aging].
Explore the source record for details and available documents.
Aged↗
[Multiconceptual therapy in Alzheimer's disease].
UNLABELLED: SOCIAL AND ECONOMICAL IMPACT: Alzheimer's disease is a neurodegenerative dementia raising major public health concern in industrialized countries. The consequences are not only medical but also social and economical. PERSPECTIVES: It is thus important to establish diagnostic principles, therapeutic goals, and global strategies guiding the behavior of physicians, family and patients faced with this dreaded disease. Currently, only a few rare symptomatic treatments are available, but research in this field points to potentially effective preventive and etiopathogentic therapeutic protocols associating drugs, social support, and psychotherapy.
Alzheimer Disease↗
Serotonin transporter (5-HTT) gene polymorphism in psychogeriatric patients.
Several studies have attempted to confirm an association between a deletion/insertion polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and Alzheimer's disease independent from the apolipoprotein E (APOE) varepsilon4 status. We examined this deletion/insertion polymorphism of the serotonin transporter gene in a sample of 222 consecutively recruited gerontopsychiatric patients which was divided into four different diagnostic groups: Alzheimer's disease (N=84), mild cognitive impairment (N=29), subjective cognitive complaints (N=49), depression/other psychiatric disorders (N=56) and 118 healthy, non-demented controls. The aim of this approach was to test whether the investigated polymorphism has a high enough selectivity and specificity to distinguish between the different gerontopsychiatric disorders or to differentiate genetically AD from other forms of dementia, respectively. We could not detect any significant differences in the allelic distribution of the deletion/insertion polymorphism of the 5-HTT gene between the four patient subgroups and the control group. This finding indicates that the serotonin transporter does not appear to be a major susceptibility factor in the pathophysiology of Alzheimer's disease and other psychogeriatric disorders.
Aged↗
Combined assessment of tau and neuronal thread protein in Alzheimer's disease CSF.
OBJECTIVE: Comparative study of CSF levels of tau and AD7C-neuronal thread protein (NTP) in patients with AD and control subjects. BACKGROUND: AD is characterized by neurofibrillary tangles composed of the abnormally hyperphosphorylated microtubule-associated protein tau. AD7C-NTP is a proposed AD marker expressed at early stages of neurofibrillary degeneration. METHODS: Enzyme-linked immunosorbent assays specific for tau and AD7C-NTP. CSF samples were obtained from 35 demented patients (25 with antemortem clinical diagnosis of probable AD, 5 with neuropathologic diagnosis of definite AD, 5 with Lewy body pathology), 29 nondemented patients with PD, and 16 elderly healthy control subjects. Receiver operating characteristics (ROC) and multivariate discriminant analysis for AD versus controls. Correlational analysis of CSF tau and AD7C-NTP and of each marker with Mini-Mental State Examination (MMSE) scores was performed. RESULTS: Levels of both tau and AD7C-NTP were significantly elevated in the AD patients compared with control subjects. ROC analysis showed that CSF tau distinguished between patients with AD and nondemented control subjects with 63% sensitivity and 89% specificity, AD7C-NTP with 70% sensitivity and 87% specificity. Combined evaluation of both markers with discriminant analysis raised the specificity to 93% at a 63% sensitivity level. Both markers positively correlated with each other within the AD group, but not among control subjects. CSF levels of AD7C-NTP, but not of tau, showed a small but significant inverse correlation (r = -0.43) with MMSE scores of AD patients. CONCLUSIONS: CSF levels of tau and AD7C-NTP may be useful biomarkers for AD.
Aged↗
Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis.
Germline PTEN mutations cause Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR), two hamartoma-tumour syndromes, and somatic PTEN alterations have been shown to participate, to a greater or lesser extent, in a wide variety of sporadic neoplasia. PTEN is a tumour suppressor and dual-specificity phosphatase which affects apoptosis via its lipid phosphatase activity in the phosphoinositol-3-kinase and AKT pathway as well as inhibiting cell spreading via the focal adhesion kinase pathway. CS and BRR share some features, such as hamartomas and lipomatosis. To determine whether other syndromes characterized by overgrowth and lipomas are part of the PTEN syndrome spectrum, we ascertained six individuals with overgrowth and lipomas but who did not meet the diagnostic criteria for CS or BRR. Five had Proteus syndrome and one, a Proteus-like syndrome. When germline DNA and DNA from at least one involved tissue per case were examined for PTEN mutations, only the Proteus-like patient was found to harbour a germline R335X mutation. Interestingly, a lipomatous mass, an epidermoid naevus and arteriovenous malformation tissue, all of which were sampled from physically distinct sites, were all found to carry a second hit R130X mutation on the allele opposite the germline R335X. Both mutations have been described in CS and BRR. We postulate that the second hit, R130X, occurred early in embryonic development and may even represent germline mosaicism. Thus, PTEN may be involved in Proteus-like syndrome with its implications for cancer development in the future.
Arteriovenous Malformations↗
Alzheimer's disease, depression and normal ageing: merit of simple psychomotor and visuospatial tasks.
INTRODUCTION: A brief psychometric test battery was used to differentiate Alzheimer's disease (AD) patients from patients with depression and healthy age-matched control subjects. The purpose was to investigate the discriminative value of simple psychomotor and visuospatial tasks that were implemented in a computer-assisted test battery. METHODS: Manumotoric coordination, discrimination reaction time and performance on a visuospatial pattern-matching task were assessed. Subjects were 30 patients with the diagnosis of probable AD (mild to moderate), 22 patients with a major depression and 15 healthy normal control subjects. RESULTS: Discrimination reaction time separated the three groups most distinctly, but general level of cognitive functioning was a significantly confounding variable. There were no differences between the AD and the depressed patients when the MMSE was used as a covariate. Substantial deficiencies in manumotoric coordination were found in both demented and depressed patients. The visual pattern-matching task yielded longer reaction times in both patient groups than in the control group. CONCLUSION: Translated into neuropsychological terms, these data suggest deficiencies in basic central operations, a slowing of central information processing and attentional deficits in AD and depressed patients. Psychomotor tasks were able to distinguish effectively healthy elderly persons from AD and depressed patients. This test battery, however, appears to be limited in differentiating AD from depression.
Aged↗
Epigenetic PTEN silencing in malignant melanomas without PTEN mutation.
A tumor suppressor gene at 10q 23.3, designated PTEN, encoding a dual specificity phosphatase with lipid and protein phosphatase activity, has been shown to play an important role in the pathogenesis of a variety of human cancers. Germline mutations in PTEN cause Cowden syndrome (CS), which is characterized by multiple hamartomas and a high risk of breast and thyroid cancers. Frequent loss of heterozygosity at 10q is found in both early and advanced-stage sporadic melanomas; however, mutations or deletions in PTEN are detected mainly in melanoma cell lines. In this study, we examined PTEN expression in 34 unselected sporadic melanomas (4 primary melanomas, 30 metastases) using immunohistochemistry and correlated this with the results of structural studies of this gene. Immunostaining of 34 melanoma samples revealed no PTEN expression in 5 (15%) and low PTEN expression in 17 (50%), whereas the rest of the tumors (35%) had high levels of expression. Hemizygous deletion was found in 32% of the tumors but neither intragenic PTEN mutation nor biallelic deletion was found in any of the samples. Of the 5 melanomas showing no PTEN expression, 4 had no mutation or deletion of PTEN. Of the 13 tumors having weak PTEN immunoreactivity and informative loss of heterozygosity results, 6 had evidence of hemizygous allelic loss of PTEN while the remaining 7 had intact PTEN. These results strongly support PTEN as a major tumor suppressor on 10q involved in melanoma tumorigenesis and suggest an epigenetic mechanism of biallelic functional inactivation not previously observed in other cancers where PTEN might be involved.
DNA Mutational Analysis↗
The neurometabolic landscape of cognitive decline: in vivo studies with positron emission tomography in Alzheimer's disease.
Alzheimer's disease, the most common form of dementia in the elderly, is characterized by the progressive, global and irreversible deterioration of cognitive abilities. The development of positron emission tomography (PET) methodologies has made it possible to study the in vivo brain metabolic correlates of human cognitive and behavioral functions. Moreover, as PET scan examinations can be repeated, the progression of the neuropathological process and its relation to cognitive dysfunction can be followed over time. In an effort to understand the changes in neural function that precede and accompany onset of dementia and their relation to clinical manifestations, in the last several years, we have conducted clinical, neuropsychological and brain metabolic studies in groups of Alzheimer's disease patients at different stages of dementia severity or with distinct clinical pictures and in populations at risk for developing the disease. Here, we discuss the main findings and implications obtained from these studies.
Alzheimer Disease↗
Hereditary colorectal cancer: risk assessment and management.
There are at least nine major cancer susceptibility syndromes that infer an increased risk for colorectal cancer and/or colorectal polyposis; hereditary nonpolyposis colorectal cancer syndrome, Muir-Torre syndrome, Turcot syndrome, the I1307K polymorphism of the APC gene, familial adenomatous polyposis, attenuated familial adenomatous polyposis, Peutz Jeghers syndrome, juvenile polyposis, and the PTEN hamartoma tumor syndrome. As a result, the differential diagnosis of hereditary colorectal cancer can be complex. In addition, there has been a dramatic increase in the knowledge available regarding risk assessment and management of hereditary colorectal cancer syndromes. The literature was reviewed to develop this concise review of the hereditary colorectal cancer syndromes to facilitate the accurate diagnosis of each syndrome and the appropriate medical care for individuals with these diagnoses. Referral to a qualified Clinical Cancer Genetics program is appropriate if any of these syndromes is suspected and they will ensure the most up-to-date information is available to the patient, their family, and their health care professionals.
Colorectal Neoplasms↗
Corpus callosum measurement as an in vivo indicator for neocortical neuronal integrity, but not white matter pathology, in Alzheimer's disease.
Explore the source record for details and available documents.
Alzheimer Disease↗
Efficacy of a touchscreen computer based family cancer history questionnaire and subsequent cancer risk assessment.
OBJECTIVE: A computer based touchscreen family cancer history questionnaire was developed and implemented to facilitate the provision of cancer risk assessments for the ambulatory and outpatient populations of a free standing cancer hospital. METHODS: A questionnaire consisting of a series of branched point decision making screens was developed which enables the participant to enter demographic data, personal cancer history, and cancer histories for first and second degree relatives. A freestanding touchscreen computer kiosk system was used to place the questionnaire in public areas of the cancer hospital and clinic. Genetic professionals analysed the data received, using published criteria, and provided a basic cancer risk assessment and surveillance recommendations within 10 business days. A survey was completed by a small random group of users (n = 59) three to six months after receipt of their risk assessment. RESULTS: After 11 months, 1440 people had entered information and received a written communication. Only 2% of completed questionnaires contained insufficient information to provide a basic risk assessment. Of the small group of participants surveyed, almost all (95%) felt "very comfortable" using the system, 93% remembered receiving the risk assessment letter when queried three to six months later, 42% felt their perceptions about cancer risk had changed, and 20% had made changes in their or their family's cancer surveillance practices. CONCLUSION: The touchscreen computer family history questionnaire allows easy collection of family history information, provision of risk assessments to a broad population, and promotes increased awareness of familial risk and appropriate surveillance.
Cancer Care Facilities↗
Pisa syndrome (pleurothotonus): report of a multicenter drug safety surveillance project.
BACKGROUND: Pisa syndrome is usually regarded as a rare adverse event of neuroleptic medication. However, its frequency and predisposing factors have yet to be defined. Here, we investigated risk factors of Pisa syndrome occurring in a large population of psychiatric patients surveyed during a multicenter drug safety project. METHOD: Twenty episodes of Pisa syndrome were documented in 17 patients within a population of 45,000 psychiatric patients monitored by a multicenter drug safety surveillance project (Projekt zur Uberwachung der Arzneimittelsicherheit in der Psychiatrie) between 1990 and 1997. All results were related to the epidemiologic data provided for this population and systematically analyzed regarding history of medication, current medication, comedication, and clinical course. RESULTS: A constellation of putative risk factors was found in the majority of patients: previous treatment with classical neuroleptics, combined pharmacologic treatment, female gender, old age, and the presence of an organic brain disorder. Given these risk factors, Pisa syndrome was also documented with atypical neuroleptic drugs such as clozapine, olanzapine, and sertindole. CONCLUSION: We conclude that Pisa syndrome is a very rare adverse event occurring with neuroleptic treatment. In patients exhibiting the reported constellation of risk factors, neuroleptic drugs should be administered with particular caution.
Adult↗
Is the EEG helpful in diagnosing and monitoring lithium intoxication? A case report and review of the literature.
Lithium is potentially toxic to the central nervous system. Clinical lithium neurotoxicity may appear at any time during therapy and may go unrecognized. Failure to appreciate this fact leads to delays in diagnosis and treatment, placing the patient at risk of permanent neurological damage or death. In spite of a largely clinical diagnosis of lithium intoxication, the EEG provides an objective criterion of intoxication. We report a case of lithium intoxication with neurotoxic symptoms associated with marked EEG changes despite moderate lithium serum levels. In contrast to the interindividually varying EEG changes under uncomplicated lithium therapy, pathological EEG findings are the rule in the case of intoxication. Several reports evince a closer relationship between neurotoxic symptoms with EEG changes than with serum levels of lithium. This is of clinical interest with respect to intoxication under therapeutic lithium serum levels, since the EEG is the only examination indicating an intoxication. In patients with intoxication, the phenomenon of long-lasting EEG changes after discontinuation of lithium is discussed with respect to neuronal storing of lithium and persisting neurological disturbances.
Aged↗