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C Hock

Publications and source records attributed to C Hock.

At least 19 recordsLinked to original sources
PubMed2005

Consensus paper of the WFSBP Task Force on Biological Markers of Dementia: the role of CSF and blood analysis in the early and differential diagnosis of dementia.

Aging of population, and increasing life expectancy result in an increasing number of patients with dementia. This symptom can be a part of a completely curable disease of the central nervous system (e.g, neuroinflammation), or a disease currently considered irreversible (e.g, Alzheimer's disease, AD). In the latter case, several potentially successful treatment approaches are being tested now, demanding reasonable standards of pre-mortem diagnosis. Cerebrospinal fluid and serum analysis (CSF/serum analysis), whereas routinely performed in neuroinflammatory diseases, still requires standardization to be used as an aid to the clinically based diagnosis of AD. Several AD-related CSF parameters (total tau, phosphorylated forms of tau, Abeta peptides, ApoE genotype, p97, etc.) tested separately or in a combination provide sensitivity and specificity in the range of 85%, the figure commonly expected from a good diagnostic tool. In this review, recently published reports regarding progress in neurochemical pre-mortem diagnosis of dementias are discussed with a focus on an early and differential diagnosis of AD. Novel perspectives offered by recently introduced technologies, e.g, fluorescence correlation spectroscopy (FCS) and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) are briefly discussed.

Aged↗
PubMed2004

Frontotemporal dementia: impact of P301L tau mutation on a healthy carrier.

Frontotemporal dementia (FTD) is the second commonest form of dementia after Alzheimer's disease, but its clinical and biological features are less well known. To uncover its earliest signs, we studied the main clinical, neuroimaging, and biochemical findings in an asymptomatic carrier from a three generation FTD family, bearing the P301L pathogenic mutation in the tau gene. Except for selective impairment on the Verbal Fluency Test for letters, all cognitive tests were normal. The brain computed tomography scan was normal, but the brain single photon emission computed tomography and statistical parametric mapping (SPECT-SPM) scan revealed bilateral frontal lobe hypoperfusion. Levels of total tau, 181P-tau, and Abeta1-42 in the cerebrospinal fluid were increased compared with control values. We conclude that detection of these distinctive abnormalities should improve early diagnostic accuracy for FTD and help distinguish it from Alzheimer's disease.

Adolescent↗
PubMed2003

Association of late-onset Alzheimer disease with a genotype of PLAU, the gene encoding urokinase-type plasminogen activator on chromosome 10q22.2.

Urokinase-type plasminogen activator (uPA) converts plasminogen to plasmin. Plasmin is involved in processing of amyloid precursor protein and degrades secreted and aggregated amyloid-beta, a hallmark of Alzheimer disease (AD). PLAU, the gene encoding uPA, maps to chromosome 10q22.2 between two regions showing linkage to late-onset AD (LOAD). We genotyped a frequent C/T single nucleotide polymorphism in codon 141 of PLAU (P141L) in 347 patients with LOAD and 291 control subjects. LOAD was associated with homozygous C/C PLAU genotype in the whole sample (chi2=15.7, P=0.00039, df 2), as well as in all sub-samples stratified by gender or APOE epsilon4 carrier status (chi2> or = 6.84, P< or =0.033, df 2). Odds ratio for LOAD due to homozygosity C/C was 1.89 (95% confidence interval 1.37-2.61). PLAU is a promising new candidate gene for LOAD, with allele C (P141) being a recessive risk allele or allele T (L141) conferring protection.

Age of Onset↗
PubMed2003

Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization.

BACKGROUND: AD is characterized by cerebral deposition of beta-amyloid plaques with amyloid beta-peptide (Abeta) 42 as the major peptide constituent, along with neurofibrillary tangles and neuronal loss. In transgenic mice, active immunization against Abeta42 removes these plaques and improves cognitive function. A Phase I study in AD patients demonstrated good safety and tolerability of multiple injections of aggregated Abeta42 (AN1792) with QS-21 as adjuvant. METHODS: Three hundred seventy-two patients with mild to moderate AD were randomized to receive IM injections of AN1792 or placebo (4:1) at baseline and at months 1, 3, 6, 9, and 12 in a multicenter Phase II safety, tolerability, and pilot efficacy study. Dosing was terminated after four early reports of meningoencephalitis, but follow-up continued. The study remains blinded, and further results will be reported after its termination. RESULTS: Symptoms and laboratory findings consistent with meningoencephalitis occurred in 18 of 298 (6%) patients treated with AN1792 compared with 0 of 74 on placebo (p = 0.020). Sixteen of the 18 had received two doses, one had received one dose, and one had received three doses of the study drug before symptoms occurred. The median latency from the first and last injections to symptoms was 75 and 40 days. No case occurred later than 6 months after the first immunization. Anti-Abeta42 antibody titers were not correlated with the occurrence or severity of symptoms or relapses. Twelve patients recovered to or close to baseline within weeks, whereas six remain with disabling cognitive or neurologic sequelae. All 18 patients remain alive to date (December 31, 2002), 6 months to >1 year after symptom onset. CONCLUSIONS: Postvaccination meningoencephalitis occurred without clear relation to serum anti-Abeta42 antibody titers. Potential mechanisms such as T-cell and microglial activation may be responsible and are under consideration to develop a safer anti-Abeta immunotherapy for AD.

Adrenal Cortex Hormones↗
PubMed2003

Genetic association of acyl-coenzyme A: cholesterol acyltransferase with cerebrospinal fluid cholesterol levels, brain amyloid load, and risk for Alzheimer's disease.

A common polymorphism of the gene encoding acyl-coenzyme A: cholesterol acyltransferase 1 (SOAT1), which is involved in the regulation of beta-amyloid peptide generation, is associated with low brain amyloid load (P=0.03) and with low cerebrospinal fluid levels of cholesterol (P=0.005). This polymorphism of SOAT1 is also associated with reduced risk for Alzheimer's disease in ethnically distinct populations (P=0.0001, odds ratio: 0.6, 95% confidence interval 0.4-0.8).

Aged↗
PubMed2003

Saitohin gene is not associated with Alzheimer's disease.

BACKGROUND: The deposition of tau protein in neurofibrillary tangles constitutes an important feature of many neurodegenerative disorders, including Alzheimer's disease. A polymorphic gene, saitohin (STH), nested within the tau gene (microtubule associated protein tau, MAPT), was recently identified and an association of a non-synonymous polymorphism in STH with increased risk for Alzheimer's disease was suggested. OBJECTIVE AND METHODS: To test the above hypothesis in a case-control association study of two independent white populations within Switzerland and Greece, comparing genotype and allele frequencies from 225 Alzheimer's disease patients and 144 healthy control subjects. RESULTS: No differences in allelic or genotypic distributions between Alzheimer's disease patients and controls was found in the individual samples (Swiss/Greek) or in the combined sample. Stratification for the presence of apolipoprotein E (APOE) epsilon 4 allele, sex, or age did not show significant effects in the populations studied, nor was there an effect on the age of onset. CONCLUSIONS: No evidence was found for an association of the non-synonymous polymorphism (Q7R) in STH and Alzheimer's disease. This finding is in line with earlier studies showing no association between MAPT and Alzheimer's disease.

Aged↗
PubMed2002

Galantamine provides broad benefits in patients with 'advanced moderate' Alzheimer's disease (MMSE < or = 12) for up to six months.

We investigated whether galantamine (Reminyl), a cholinergic agent with a dual mode of action for the treatment of mild to moderate Alzheimer's disease (AD), would benefit patients with more advanced illness. We performed a post hoc analysis on pooled data from four pivotal studies in patients with 'advanced moderate' AD: baseline Mini-Mental State Evaluation (MMSE) scores < or = 12 (range 10-12; mean MMSE score 11) or Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores >30 (range 31-69; mean ADAS-cog score 39). Over 5-6 months, cognitive abilities were improved with galantamine versus placebo (p<0.001; mean treatment difference 6.5 points). At 6 months, galantamine benefited functional abilities (p<0.001 vs placebo). The first quartile of galantamine patients improved over baseline by 10.5 ADAS-cog points. Cognitive and functional abilities were maintained around baseline; behavioural symptoms were delayed. Over 6 months, galantamine provided a broad spectrum of benefits to patients with 'advanced moderate' AD.

Aged↗
PubMed2001

[Rational therapy of Alzheimer dementia based on current clinical studies].

Several preparations are currently available for the treatment of Alzheimer's dementia. To date only some of these drugs could show evidence of efficacy that would justify a recommendation for their therapeutic use. In the present survey, the results of five controlled clinical trials with acetylcholinesterase inhibitors versus Ginkgo-biloba extract have been analysed. The trials conducted with the acetylcholinesterase altogether have a larger patient population, an acceptable significance level of therapeutic effect as well as a lower rate of drop outs. Based on the documentation presented here, only the approved acetylcholinesterase inhibitors are currently to be recommended under strict scientific criteria for use in the treatment of Alzheimer's dementia.

Activities of Daily Living↗
PubMed2001

Non-replication of association between cathepsin D genotype and late onset Alzheimer disease.

In two recent studies from Germany, a strong association was found between the allelic variant T of the amino acid substitution encoding polymorphism 224 C/T (A38V) in exon 2 of the cathepsin D gene (CTSD) and late onset Alzheimer disease (AD). Other studies from Europe and the USA revealed ambiguous results. Therefore, we performed an independent association study on CTSD and AD in a sample of 324 Caucasian patients from Germany, Switzerland, and Italy with late onset AD, and 302 non-demented controls. We could not confirm an association between CTSD genotype and AD, although there was a slight but not significant increase in frequency of the T allele and T carrier status in AD. Post hoc data analyses suggested that there might be a stronger effect of CTSD genotype on AD risk in males, and an interaction between CTSD and APOE genotypes in males but not females.

Age Factors↗
PubMed2000

[Diagnosis and therapy of behavior disorders in dementia].

Alzheimer's disease is one of the most common brain disorder in the elderly. In most patients who develop dementia the core syndrome of cognitive dysfunction is superimposed over the course of the disease by behavioral disorders that manifest at least temporarily to varying degrees. These include depression, anxiety, agitation, restlessness, aggression, disturbances of the sleep-wake cycle, delusions and hallucinations. Classical psychiatric exploration can be complemented by the use of the Neuropsychiatric Inventory (NPI) which allows structured diagnosis and comparative documentation of the clinical course. The majority of psychotropic drugs used in psychogeriatics have not been specifically developed for or tested in elderly, often multimorbid patients. Substances used in psychogeriatrics are subject to special requirements due to the pharmacokinetic and pharmacodynamic changes specific to very old persons. They must show clinical efficacy and a low rate of cardiovascular, peripheral and central anticholinergic effects, a low delirogenic potential and favorable pharmacokinetic and pharmacodynamic properties. Most of the newer atypical neuroleptics (e.g. risperidone) and the newer antidepressants (e.g. from the class of selective serotonin reuptake inhibitors, SSRIs, or selective serotonin and noradrenaline reuptake inhibitors, SNRIs) tend to fulfill these criteria better than the high-potency neuroleptics of the butyrophene type (e.g. haloperidol) or the tricyclic antidepressants. For that reason, these newer products should usually be preferred over the conventional agents.

Aged↗
PubMed2000

Increased CSF levels of nerve growth factor in patients with Alzheimer's disease.

The authors quantitated CSF levels of nerve growth factor (NGF) in patients with AD, nondemented control subjects (CTR), and age-matched patients with major depression (DE). CSF levels of NGF were markedly higher in the AD group than in both the CTR and DE groups (p < 0.01 and p < 0.001). Increased CSF levels of NGF in AD patients may reflect reported accumulation of NGF in the AD brain and may constitute a candidate marker for clinical diagnosis and therapeutic monitoring.

Adult↗
PubMed2000

[Alzheimer dementia].

Alzheimer's disease is the most common form of dementia in the elderly. This review describes diagnosis, differential diagnosis, etiology and course of Alzheimer's dementia. Genetic and non-genetic risk factors are presented. In addition to the already available symptomatic therapies with acetylcholinesterase-inhibitors, new therapeutic approaches with protective and restorative substances are currently being developed.

Aged↗
PubMed2000

Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease.

OBJECTIVE: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). DESIGN: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. SETTING: The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany. PARTICIPANTS: Five hundred seventeen patients with AD and 390 control subjects. MEASURES: Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects. RESULTS: Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival. CONCLUSIONS: CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.

Age of Onset↗
PubMed2000

Region-specific neurotrophin imbalances in Alzheimer disease: decreased levels of brain-derived neurotrophic factor and increased levels of nerve growth factor in hippocampus and cortical areas.

BACKGROUND: Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5) are members of the neurotrophin gene family that support the survival of specific neuronal populations, including those that are affected by neurodegeneration in Alzheimer disease (AD). OBJECTIVE: To determine whether neurotrophin protein levels are altered in the AD-affected brain compared with control brains. METHODS: We quantitated protein levels of NGF, BDNF, NT-3, and NT-4/5, and calculated neurotrophin/NT-3 ratios in AD-affected postmortem hippocampus, frontal and parietal cortex, and cerebellum, and compared them with age-matched control tissue (patients with AD/controls: hippocampus, 9/9 cases; frontal cortex, 19/9; parietal cortex, 8/5; and cerebellum, 5/7, respectively). We applied highly sensitive and specific enzyme-linked immunosorbent assays in rapid-autopsy-derived brain tissue (mean+/-SD postmortem interval, 2. 57+/-1.75 h, n=71) to minimize postmortem proteolytic activity. RESULTS: Levels of BDNF were significantly reduced in hippocampus and parietal cortex (P<.001, and P<.01) as well as BDNF/NT-3 ratios in frontal and parietal cortices (P<.05, and P<.01) in the group with AD compared with the control group. Levels of NGF and NGF/NT-3 ratio were significantly elevated in the group with AD compared with the control group in the hippocampus and frontal cortex (P<.001). Levels of NT-4/5 and the NT-4/NT-3 ratio were slightly reduced in hippocampus and cerebellum in the group with AD compared with the control group (P<.05). In contrast, the levels of NT-3 were unchanged in all brain regions investigated. CONCLUSION: Decreased levels of BDNF may constitute a lack of trophic support and, thus, may contribute to the degeneration of specific neuronal populations in the AD-affected brain, including the basal forebrain cholinergic system. Arch Neurol. 2000.

Adult↗
PubMed2000

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↗
PubMed2000

Increased cerebrospinal fluid levels of neurotrophin 3 (NT-3) in elderly patients with major depression.

Neurotrophin 3 (NT-3) is a member of the neurotrophin gene family which supports the survival of specific neurons. NT-3 was shown to prevent the death of adult central noradrenergic neurons in vivo, a neuronal population which is associated with the pathophysiology of major depression. We quantitated CSF levels of NT-3 in elderly patients with major depression (DE) and compared them to patients with Alzheimer's disease (AD), and mentally healthy control subjects (CTR). CSF levels of NT-3 were markedly and significantly elevated in the DE group, as compared to either the AD or the CTR group (P < 0.01, and P < 0.001, respectively). In terms of diagnostic accuracy, measurement of NT-3 levels in DE resulted in 73.9% sensitivity, and 89.7% specificity. Increased CSF levels of NT-3 may indicate a disturbance of the central noradrenergic system in patients with DE. NT-3 may constitute a biochemical candidate marker for clinical diagnosis and for the evaluation of therapeutic strategies in DE.

Adult↗