Bihemispheric cerebral FDG PET correlates of cognitive dysfunction as assessed by the CERAD in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by a variety of cognitive deficits which can be reliably assessed by the neuropsychological test battery of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), but the cerebral changes underlying the respective cognitive deficits are only partly understood. Measures of severity of dementia in AD as well as delayed episodic memory performance in mild cognitive impairment significantly correlated with bihemispheric cerebral glucose hypometabolism. We therefore hypothesized that the CERAD cognitive battery may represent cerebral dysfunction of both hemispheres in patients with AD. In 32 patients with AD, cerebral glucose metabolism was investigated using positron-emission-tomography with 18Fluorodeoxyglucose (FDG PET) and associated with the test scores of the CERAD cognitive battery by statistical parametric mapping. Episodic memory scores significantly correlated with temporopari etal glucose metabolism of both hemispheres while delayed episodic memory significantly was correlated with the right frontotemporal cortices. Verbal fluency and naming scores significantly correlated with glucose metabolism in left temporoparietal and right frontal cortices, whereas constructional praxis predominantly correlated significantly with the bilateral precuneus. In conclusion, the results of our study demonstrate that not only memory function but also functions of language and constructional praxis in AD are associated with glucose metabolism as revealed by FDG PET in subsets of uni- and bilateral brain areas. The findings of our study for the first time demonstrate that in AD neuropsychological deficits as assessed by the CERAD refer to different cerebral sites of both hemispheres.

Neural correlates of delayed episodic memory in patients with mild cognitive impairment--a FDG PET study.

Mild cognitive impairment (MCI) is characterized by cognitive deficits which do not yet reach the threshold of dementia but represent a putative preclinical state of Alzheimer's disease (AD). Little is known about the neural correlates of delayed episodic memory which is among the earliest signs of cognitive decline in patients at risk of developing AD. We performed resting state positron emission tomography (PET) with (18)Fluorodeoxyglucose (FDG) in patients with MCI, and hypothesized a correlation between delayed episodic memory performance and frontal glucose metabolism since the latter is relatively spared in the preclinical phase of the disease. 43 patients (age: 69.7+/-7.9 years; 24 male, 19 female) with MCI were investigated by FDG PET. Significant positive correlations with delayed episodic memory performance were calculated by statistical parametric mapping. To our knowledge the present study is the first to demonstrate by FDG PET the neural correlates of delayed episodic memory in patients with MCI. Our study revealed a pattern of cerebral glucose metabolism including bifrontal regions which may contribute to the delayed episodic memory performance of patients with MCI. Since not all patients with MCI will further deteriorate, AD specific mechanism may not be concluded from the present study but warrant longitudinal investigations.

[CSF levels of total tau protein in patients with mild cognitive impairment and Alzheimer's disease]. / Tauproteinspiegel bei Patienten mit leichter kognitiver Beeinträchtigung und Alzheimer-Demenz.

In recent studies, patients diagnosed with Alzheimer's disease (AD) showed significantly elevated CSF levels of tau protein. Tau protein was therefore regarded as a putative molecular marker for AD. Since early diagnosis of AD is warranted for appropriate therapeutic intervention, investigation of total tau protein levels in patients with Aging Associated Cognitive Decline (AACD) and AD are reasonable. In our study the CSF concentrations of total tau protein were measured by ELISA in 132 patients with AD, 29 patients with AACD and 24 healthy controls. CSF concentrations were compared between the subgroups of mild, moderate and severe AD, AACD and the control group and were correlated with age and severeness of the illness. The concentration of total tau protein was increased significantly in patients with severe and moderate AD compared to all other groups. Within the group of AD patients, total tau protein correlated significantly with the severity of the dementia but not with age. Although the range of the measured tau protein concentrations is wide and overlapping between the diagnostic groups our data indicate that from a clinical point of view significantly increased tau protein levels confirm the clinical diagnosis of AD while normal values do not exclude it.

Reliability and validity of the Knowledge about Depression and Mania Inventory.

BACKGROUND: The knowledge that patients with affective disorders have about their illness is attributed increasing importance. For a number of psychiatric disorders, the imparting of information about the illness is now standard treatment. However, the relevance of knowledge about a patient's disorder has to date not been sufficiently studied. One reason for that is that only few psychometrically validated instruments for the assessment of illness knowledge exist. The aim of this study was the development and psychometric evaluation of a questionnaire to assess knowledge about affective disorders. METHODS: The Knowledge about Depression and Mania Inventory (KDMI) was evaluated with a sample of 337 patients with major depression, relatives of patients with depression and schizophrenia, and controls. RESULTS: With the 44-item KDMI, the 3 dimensions knowledge of symptoms, knowledge of treatment and knowledge of coping strategies were differentiated. From these 44 items two 22-item parallel tests were developed for follow-up assessment. The scales showed good internal consistency. There were numerous indicators of the validity and sensitivity to change of the scales. It was shown that older patients and patients with lower levels of education are less knowledgeable about affective disorders. There were significant differences in the scales of the KDMI before and after a psychoeducative group for relatives. CONCLUSIONS: The study showed that knowledge about affective disorders can be reliably and validly measured by a questionnaire. Because of its brevity the KDMI is suitable for everyday use in clinical practice, and it forms the basis for further investigation of the significance of illness knowledge, as well as for evaluation of the effects of psychotherapy in this area.

Reduced cerebral glucose metabolism in patients at risk for Alzheimer's disease.

While significantly reduced glucose metabolism in fronto-temporo-parietal and cingulate cortices has been demonstrated in Alzheimer's disease (AD) compared with controls, cerebral glucose metabolism in patients with mild cognitive impairment who subsequently develop AD is less well-defined. In the present study we measured cerebral glucose metabolism by positron emission tomography (PET) with (18)F-2-fluoro-2-deoxy-D-glucose in 14 patients with aging-associated cognitive decline (AACD), 44 patients with AD, and 14 healthy control subjects at baseline. The AACD patients were clinically followed up, and conversion to AD was determined. Compared with controls, AACD patients had significantly reduced glucose metabolism in the right precuneus, posterior cingulate, right angular gyrus, and bilateral middle temporal cortices, while the respective deficits were more pronounced in AD patients and also involved the frontal cortices. AACD patients who subsequently converted to AD (AACD-converters) showed more extended metabolic changes which also involved the frontal and temporal cortices, right cingulate gyrus, right thalamus, and bilateral precuneus.

Influence of delayed CSF storage on concentrations of phospho-tau protein (181), total tau protein and beta-amyloid (1-42).

It is generally accepted that cerebrospinal fluid (CSF) biomarkers such as tau protein, phosphorylated tau protein (threonine 181) and beta-amyloid (1-42) can facilitate early and differential diagnosis of Alzheimer's disease (AD). Since the respective concentrations can only be measured in a number of specialized centers, time to CSF specimen work-up has been considered as crucial for the stability of the respective biomarkers. When shipping of CSF samples is needed for biomarker measurement and immediate freezing of samples is not available, an overnight delay of up to 24h frequently occurs. Therefore, we investigated the potential impact of a 24h delayed freezing on CSF biomarker concentrations and compared it to 2h storage (room temperature, 20 degrees C) and an immediate freezing. First, storage at room temperature for 2h had only marginal, non-significant effects on the concentrations of CSF total tau protein and phospho-tau protein (181) compared to immediate freezing. Second, storage at room temperature for 24h did not significantly affect total tau protein or phospho-tau protein but beta-amyloid (1-42) concentrations which increased significantly compared to the samples frozen immediately. These results indicate that CSF samples for the evaluation of total tau and phospho-tau protein may be kept at room temperature for up to 24h whereas CSF samples for beta-amyloid (1-42) need to be frozen immediately.

Psychosocial factors associated with knowledge about affective disorders in patients with depression.

BACKGROUND: Increasing importance is attributed to the knowledge that patients have concerning their illness. For psychiatric disorders, imparting information about the illness has become a standard part of treatment. Despite the great clinical relevance of knowledge about depression, only few empirical studies on this subject have been carried out. This study aimed to identify psychosocial factors associated with greater or lesser knowledge about affective disorders. METHODS: Sixty-one in-patients with depression were recruited and tested with the Knowledge about Depression and Mania Inventory. RESULTS: Almost all patients sought specific information about their disorder prior to admission to hospital. There were large differences in patients' knowledge about the disorder and their choice of information source. Older and less educated patients had less knowledge about affective disorders. Patients with less illness knowledge also have a less favourable illness concept, poorer interpersonal relationships and more passive coping strategies. CONCLUSIONS: The results show that knowledge about affective disorders is a central illness characteristic that has numerous implications for the ability to cope with the disorder, as well as for psychotherapeutic management. The results contribute to a clarification of the relationship between psychoeducation and psychotherapy.

CSF tau protein and FDG PET in patients with aging-associated cognitive decline and Alzheimer's disease.

INTRODUCTION: In Alzheimer's disease (AD), accelerated neurofibrillary tangle formation occurs which is associated with increased tau protein release into the cerebrospinal fluid (CSF). Recent studies found significantly increased CSF tau already in patients at risk of developing AD, indicating its potential as a biochemical marker of AD. Cerebral glucose metabolism is reduced in frontotemporoparietal and cingulate cortices in patients with mild AD. However, few studies have investigated CSF tau protein and cerebral glucose metabolism changes in patients at risk to develop AD. METHODS: 48 patients with AD, 88 patients with aging-associated cognitive decline (AACD), and 39 healthy controls were included. In all participants, CSF levels of tau were determined by ELISA at baseline and compared between the diagnostic groups. 14 AACD patients and 14 controls underwent (18)F-fluorodeoxyglucose positron emission tomography (FDG PET). RESULTS: AD patients showed the highest CSF tau levels compared with AACD patients and controls. AACD patients had significantly higher tau levels than the controls but lower than the AD patients. AACD patients were characterized by reduced glucose metabolism in bilateral middle temporal cortex, left posterior cingulate cortex, right angular gyrus, and right precuneus compared with controls. CONCLUSION: In conclusion, our findings reflect and confirm the clinical judgment of an incipient neurodegenerative disorder in a considerable portion of AACD patients. In patients with AACD, CSF tau levels and cerebral glucose metabolism show an altered pattern comparable with that found in AD and thus may facilitate early diagnosis.

Dimensions of the Typus melancholicus personality type.

The Typus melancholicus personality type (TMP) is characterised by orderliness, conscientiousness and interpersonal dependence. Several standardised instruments have been developed for the assessment of the Typus melancholicus personality. To date there has been no systematic comparison of these instruments and in particular it has been unclear whether TMP represents a single trait or a personality trait constellation. The aim of this study was the comparison of four TMP questionnaires and the investigation of the dimensionality of the personality as revealed by these questionnaires. The factorial validity of four TMP questionnaires was examined based on a sample of n = 264 psychiatric inpatients and normal controls. In a factor analysis of the items of the TMP questionnaires, four dimensions could be differentiated: Dependence, Intolerance of Ambiguity, Norm-Orientation, and Perfectionism. Psychometric evaluation showed good values for the individual items and the new TMP scales. The four subscales had a differential correlation profile in relation to the dimensions of the five-factor model of personality. The TMP scales could distinguish a group of depressed patients from a group of normal controls. The results show that TMP personality is not a single trait but consists of four related but separate traits. These can be clearly distinguished from those of the five-factor model of personality. The analysis of the TM concept therefore also represents a theoretical perspective for the integration of the personality characteristics which are relevant for depression. Based on this analysis, we constructed a multidimensional TMP inventory which forms the basis for the investigation of the effect of TM personality on clinical outcome and on psychotherapeutic treatment.

Interactive regulation of affect in postpartum depressed mothers and their infants: an overview.

Specific patterns of interaction emerging in the first months of life are related to processes regulating mutual affects in the mother-child dyad. Particularly important for the dyad are the matching and interactive repair processes. The interaction between postpartum depressed mothers and their children is characterized by a lack of responsiveness, by passivity or intrusiveness, withdrawal and avoidance, as well as a low level of positive expression of affect. Thus, an impaired capability to regulate the child's affect has been demonstrated in depressed mothers. Maternal aggression, neglect toward infants, infanticidal thoughts, as well as infanticidal behavior are mainly linked to severe postpartum depression, especially with psychotic symptoms. The findings on mother-child interaction reported in this paper are based on mothers with mild to moderate depressive disorders without psychotic symptoms. Considering the stability of interaction patterns in the course of depressive illness as well as the long-term consequences of these interactions, it seems surprising that there are still few systematic studies of depressed mothers interacting with their infants. In connection with an overview on these issues, treatment models for parent-infant psychotherapy are discussed.

Hippocampal glucose metabolism is associated with cerebrospinal fluid estrogen levels in postmenopausal women with Alzheimer's disease.

Animal studies indicate that estrogens, such as 17beta-estradiol (E(2)), may enhance hippocampal metabolism and function. In postmenopausal Alzheimer's disease (AD) patients, cerebrospinal fluid (CSF) E(2) levels were significantly lower than in non-demented controls. This finding was inversely correlated with CSF beta-amyloid levels. To address the potential impact of this finding, E(2) levels in CSF were correlated with regional cerebral [18F]2-fluoro-2-deoxy-D-glucose (FDG) uptake as measured using positron emission tomography (PET) in six postmenopausal AD patients. CSF E(2) levels were determined using an electro-chemiluminescence-immunoassay on the Roche Elecsys 2010 immunoassay analyzer. Basic image processing was done by MEDx, using SPM routines for spatial normalization and statistics. CSF E(2) levels were significantly correlated with cerebral glucose metabolism in the left hippocampus. This is the first clinical study indicating an association between CSF E(2) concentration and hippocampal glucose metabolism in postmenopausal women with AD.

Cerebrospinal fluid tau levels in Alzheimer's disease are elevated when compared with vascular dementia but do not correlate with measures of cerebral atrophy.

Increased tau levels are a well-established finding in Alzheimer's disease (AD). In contrast, the potential value of tau levels in the differential diagnosis of AD, vascular dementia (VD) and major depression warrants further investigation. The potential impact of psychotropic medication also needs to be established. We investigated cerebrospinal fluid (CSF) tau protein concentrations in 88 patients with AD, 23 patients with VD, 25 patients with major depression and 17 age-paralleled controls without cognitive impairment with respect to important clinical variables, type and dosage of psychotropic medication and cerebral changes as assessed by magnetic resonance imaging (MRI). The AD patients showed significantly elevated tau levels compared with patients with VD or major depression and controls. Tau levels obtained in the VD group were intermediate, with significant differences from both AD patients and patients with major depression and controls. Within the AD group, no significant correlation between tau levels, severity of dementia, age, duration of disease, type and dosage of psychotropic medication or MRI volumetric changes arose. A subgroup of AD patients without increased tau levels was characterized by a significantly larger percentage of patients with presenile onset.

Cerebrospinal fluid tau protein levels in schizophrenia.

Increased cerebrospinal fluid (CSF) tau protein levels are generally considered to provide a sensitive marker of neurodegenerative processes such as Alzheimer's disease (AD). Since a more pronounced cognitive decline has been described in older schizophrenic patients, it has been hypothesized that these patients might be at a higher risk of developing AD. CSF levels of total tau protein and tau protein phosphorylated at threonine 181 (phospho-tau) were determined among 19 older and younger patients with schizophrenia compared to 20 age-matched healthy controls. No significant differences in CSF total tau and phospho-tau levels arose between patients with schizophrenia and controls. Although our results do not exclude a progressive neurodegenerative pathology, they provide evidence against major neuronal degeneration such as an AD-related pathology associated with increased tau levels in schizophrenia.

Levels of total tau and tau protein phosphorylated at threonine 181 in patients with incipient and manifest Alzheimer's disease.

Cerebrospinal fluid tau protein levels are considered to be a promising marker for Alzheimer's disease (AD) and may facilitate early detection. Using the newly developed INNOTEST Phospho-Tau((181P)) kit examination of total tau and tau protein phosphorylated at threonine 181 (phospho-tau 181) revealed significantly (P<0.05) higher values in both patients with incipient and manifest AD than in controls. In patients with vascular dementia, phospho-tau 181 levels were not different from controls but were significantly lower than in patients with manifest AD. These findings suggest that total and phosphorylated tau protein may facilitate early detection and differential diagnosis of AD.

Typus melancholicus personality type and the five-factor model of personality.

Personality traits are significant factors in the development and course of depression. Apart from the classical five-factor model of personality, other personality constellations, such as Tellenbach's Typus melancholicus, have been described in association with depressive disorder. Several instruments have been developed to assess the Typus melancholicus personality (TMP). A systematic comparison of these instruments has not been done to date. The goal of this study was the comparison of four questionnaires used in assessing TMP. Four TMP questionnaires were compared and their relationship to the five-factor model of personality was examined among 264 psychiatric patients and normal controls. It was found that the TMP type represents a trait distinct from those of the five-factor model. TMP inventories had only moderate concurrent validity. The single TMP scales focus on different aspects of the TMP, despite their common core. Both the five-factor personality traits and the TMP scales were able to differentiate a group of depressed patients from control groups. The results show that TMP is not one trait but a personality trait constellation. This leads to the conclusion that a number of dimensions must be taken into consideration in the construction of a TMP inventory. This multidimensionality contributes to the refinement of the TMP concept and differentiates its therapeutic implications.