The rate of conversion of mild cognitive impairment to dementia: predictive role of depression.

BACKGROUND: Mild cognitive impairment (MCI) is a condition referring to the persons with cognitive deficits measurable in some form or another, but not meeting criteria for dementia, and who have an increased risk of becoming demented. OBJECTIVE: To establish the rate of progression to dementia in MCI, to investigate the risk of conversion for amnestic vs multiple-domains subtypes, and to identify the predictors of progression. METHODS: MCI (n = 105) individuals enrolled in a longitudinal study received annual clinical and psychometric examinations for up to a mean of 3 years. The diagnosis of MCI according to Mayo Clinic Petersen's Criteria was conducted by a panel of specialists. RESULTS: After 3 years of follow-up, 23 of 105 subjects with MCI were diagnosed with dementia. 40 showed cognitive decline not dementia, 34 were stable and showed no cognitive decline or improvement, while eight showed cognitive improvement. CONCLUSIONS: We conclude that conversion rate from MCI to DSM-IIIR dementia was 21.9% over a period of 3 years. The occurrence of depressive symptoms may constitute a predictor for those who are more likely to progress to dementia. The risk of conversion to dementia was higher among the subjects with an evidence of impairment extending beyond memory than with those who suffered only from memory deficits, and the subjects who converted to dementia in this subtype had significantly higher baseline plasma total homocysteine levels than non-converters.

Prevalence of major and minor depression in elderly persons with mild cognitive impairment--MADRS factor analysis.

OBJECTIVE: The aim of the study was to detect the prevalence of depressive syndromes and symptoms in the sample of elderly persons with Mild Cognitive Impairment (MCI), and to analyse Montgomery-Asberg Depression Rating (MADRS) item scores. METHOD: The subjects of the study were 102 consecutive out-patients with MCI. All subjects were assessed by an experienced psychiatrist and MADRS was applied. Major and minor depressive episodes were defined according to DSM-IV criteria. Factor analysis was used to analyse baseline MADRS item scores. RESULTS: Three patient groups emerged according to the depressive symptoms distribution and severity scores basis: those with major depression constituted 19.6% (n = 20), with minor depression 26.5% (n = 27), and with very few depressive symptoms 53.9% (n = 55). Three interpretable MADRS factors were identified, using the factor analysis with Varimax rotation: the first consisting of apparent and reported sadness, inability to feel, pessimistic thoughts, the second consisting of inner tension, reduced sleep, reduced appetite, suicidal thoughts, and the third with concentration difficulties and lassitude. CONCLUSIONS: It was concluded that both major and minor depression is common in MCI. Three MADRS factors were identified and labelled as anhedonia-pessimism, anxiety-vegetative, and cognitive-inhibition.

Behavioural pathology in Alzheimer's disease with special reference to apolipoprotein E genotype.

The aim of this study was to define the co-occurrence of behavioural symptoms and Alzheimer's disease (AD) in relation to apolipoprotein E (APOE) genotype. Probable AD patients from the Alzheimer's Day Clinic (n = 139) were assessed with the 'Behavioural Pathology in Alzheimer's Disease' rating scale, and their APOE genotype was determined. This study demonstrated no relationship between presence of the APOE epsilon4 allele and any of the behavioural symptoms assessed, including delusions, hallucinations, depression, activity disturbances, aggressiveness and anxiety. Activity disturbances, delusions, hallucinations and aggressiveness paralleled the severity of AD, increasing in frequency with the severity of the dementia. The prevalence of delusions, hallucinations, aggressiveness and depression were found to be associated with lower levels of education.

[Psychophysiological correlates of primary insomnia]. / Psychofizjologiczne wskazniki bezsennosci przewleklej.

Psychophysiological differences between 16 patients with primary insomnia, 7 men and 9 women, of mean age 40.8 years, and 16 controls, matched according to age, sex and education, were studied. Insomniacs differed from controls in the following results: their motor activity level was higher during night, sleep efficiency was lower and complexity in slow wave sleep was higher. The Hyperarousal Scale score was higher in insomniacs and it correlated with severity of insomnia in Athens Insomnia Scale. Sleep latency in MSLT was not shorter in patients group. Reaction time was shorter, moreover, the number of presentations necessary to memorize all items of Selective Reminding Test was greater in these patients. Degree of the learning disturbance correlated with the Athens Insomnia Scale score. No correlations were found between Selective Reminding Test and standard polysomnographic parameters. To sum up, the hypothesis on 24-hour hyperarousal in primary insomnia has been confirmed and learning impairment has been documented in the present study, independent of standard polysomnographic parameters.

Expression of vascular endothelial growth factor and basic fibroblast growth factor receptors in lung cancer.

OBJECTIVE: To determine the expression of two angiogenic factors, vascular endothelial growth factor (VEGF) and fibroblast growth factor receptors (FGFR), in non-small cell lung carcinoma (NSCLC) in relation to tumor stage (TN0, TN1, TN2) and in association with the expression of p53 protein, a potential suppressor of tumor angiogenesis. STUDY DESIGN: The immunohistochemical (IHC) expression of VEGF and FGFR was examined in paraffin sections of 56 NSCLC in relation to the presence of lymph node metastases and p53 expression. Nodal status of NSCLC determined: 27 tumors, N0; 16, N1; and 13, N2 stage. Semiquantitative analysis with a score corresponding to IHC staining intensity and percentage of positive cells was used. Statistical analysis was performed with the chi 2 test. RESULTS: A significant association was noted between VEGF and FGFR expression in NSCLC. No relation was found between VEGF, FGFR expression and lymph node metastasis or p53 expression. CONCLUSION: We assume that VEGF and FGFR act in a synergistic manner in NSCLC and that their expression is not related to lymph node metastases. Angiogenesis is a very complex phenomenon and heterogeneous within tumors. Also, it is affected by microenviromental factors.

Therapeutic drug monitoring in depression.

The difference between Therapeutic Drug Monitoring (TDM) and uncontrolled therapy consists in the fact that in TDM we can predict a certain scheme of treatment according to clinical and laboratory results. It is a method which serves to increase the efficacy and safety of pharmacotherapy in an individual patient. This paper presents the results of the treatment with tricyclic antidepressants based on the monitoring of serum drug level in 32 patients with indications for using pharmacogenetic as well as pharmacoelectroencephalographic tests. Clinical status of the patients was evaluated according to: Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Clinical Global Impression Scale (CGIS), and TCA concentration in serum was determined using Fluorescence Polarization Immunoassay (FPIA). Hydroxylation phenotype was determined using debrisoquine as a model drug. EEG was recorded in four leads: F3-C3, F4-C4, P3-O1, P4-O2. In the present study, we did not found any significant correlation between clinical status and serum TCAs concentrations measured by FPIA method. Efficacy of antidepressant treatment and stabilization of serum TCA concentrations depended largely upon the time course of the treatment. Debrisoquine phenotyping revealed the presence of one poor metabolizer (MR = 15) in the examined group of patients. A significant improvement in the clinical status of the patients, the stabilization of therapeutic drug concentrations, the appearance of antidepressive profiles in the pharmaco-EEG profile after 14 days of therapy, as well as the starting value determined by SERS were shown to be prognostic factors for the further antidepressant therapy.

Lung carcinoids. Tumor angiogenesis in relation to clinicopathologic characteristics.

OBJECTIVE: To evaluate the prognostic value of carcinoid angiogenesis for the presence of lymph node metastases, histologic subtype and tumor size. STUDY DESIGN: The study group consisted of 72 resected primary lung carcinoids, 57 typical and 15 atypical. TNM staging was performed. The histologic criteria for carcinoids was based on the Flieder classification. Angiogenesis, expressed as tumor microvessel density, was estimated in sections stained with CD34 antibody, according to Weidner's method. RESULTS: The size of carcinoids was related to the histologic type: the average tumor diameter of typical carcinoids was significantly smaller than the average diameter of atypical carcinoids (P = .003, U = 207, Z = -3.023). Atypical carcinoids represented a more aggressive form of tumors than typical carcinoids; patients with typical carcinoids developed lymph node metastases less frequently (10% vs. 33%) as compared to patients with atypical carcinoids; the difference was statistically significant (P = .032). Tumor angiogenesis failed to distinguish the histologic type of carcinoids and did not indicate the presence or absence of regional lymph node metastases; neither did pTN stage or tumor size. CONCLUSION: Angiogenesis is not a determining factor of the metastatic potential of pulmonary carcinoids.

High resolution study of sleep spindles.

OBJECTIVE: Universal high-resolution time-frequency parameterization of sleep EEG structures. METHODS: A new algorithm called Matching Pursuit was used for the decomposition of sleep EEG into waveforms chosen from a large and redundant set of functions. As a result all signal structures were parameterized in terms of their frequency, time occurrence, time span and energy. Slow wave activity and sleep spindles were identified according to neurophysiological criteria and various distributions describing their time evolution, topographical and frequency characteristics were constructed. RESULTS: Two types of sleep spindles of different topological and spectral properties were identified. High time-frequency resolution made possible separation of superimposed spindles. Cross-correlation between high- and low-frequency components of superimposed spindles revealed a fixed time-delay between them, the high-frequency component preceding the low-frequency one. CONCLUSION: The results of our study suggest that processes of generation of both types of sleep spindles are weakly coupled.

Expression of CEA and trophoblastic cell markers by lung carcinoma in association with histological characteristics and serum marker levels.

The study of tumour markers in lung cancer has focused mainly on serum-based analysis. The controversy about carcinoembryonic antigen (CEA), pregnancy specific glycoprotein 1 (SP1) and beta human chorionic gonadotropin (betahCG) production in lung carcinoma has been reported in several studies. The aims of this study were: to explore an expression of CEA, SP1 and betahCG in various histological types of lung carcinoma with respect to the grade of differentiation; and to define the relationship between tumour marker expression and serum marker concentration. Ninety two lung tumours (75 non-small cell carcinomas (NSCLC) and 17 small cell lung carcinomas (SCLC)) entered the study. Tumour marker expression was compared with the serum levels of CEA, SP1 and betahCG in 57 patients (pts) with NSCLC and four pts with SCLC. Positive immunostaining of CEA and SP1 was observed in 87% NSCLC, and betahCG was found in 24% NSCLC. In the SCLC group positive staining showed in 29% of tumours, SP1 in 51% and betahCG in 18%. Positive CEA expression ranged from 50-100% within the carcinomatous cell population (pcp) and was more characteristic for well and moderately differentiated adenocarcinomas. This finding was in contrast to squamous cell carcinomas, where the majority of tumours expressed CEA in 1-50% pcp. A significant negative correlation was noticed for adenocarcinoma between tumour expression and grade of histological differentiation for CEA (P < 0.001) and SP1 (P = 0.023). Results were not significant for squamous carcinoma. Significant differences of serum CEA concentration were noticed between adenocarcinoma and squamous carcinoma (P = 0.003). In addition, a statistically significant relation was found between serum CEA concentration and an early (I + II) and advanced (IIIa + IIIb + IV) stage of NSCLC (P = 0.031). A significant correlation was noticed when serum CEA and tumour CEA expression was compared for NSCLC (P < 0.001), and for serum betahCG and tumour betahCG (P = 0.019).

[The pattern of small cell lung carcinoma in autopsy (based on material of the Pathology Department, National Institute of Tuberculosis and Lung Diseases in Warsaw]. / Autopsyjny obraz raka drobnokomórkowego, (na podstawie materialu Zakladu Patomorfologii IGiChP w Warszawie).

The aim of this study was to review autopsy findings in small cell lung carcinoma (SCLC) patients (pts)--in order to assess the distribution of the disease at the time of death and to analyse the pattern of SCLC in relation with different therapeutic modalities. The pattern of autopsy findings was assessed in 100 pts SCLC: 85 pts after treatment with chemotherapy, with or without chest and cranial irradiation; and 15 pts without any therapy. The primary tumours were present in 59% pts (50 of 85), the residual tumour deposits were diagnosed in 32% (27 of 85) pts. The significant difference in the rate of locoregional disease was found between pts given chemotherapy and pts after combined therapy. The tumours occurred significantly more frequently in pts after chemotherapy, than in pts after chemotherapy with irradiation on the chest (75% and 41% respectively, p = 0.03). The chest irradiation with chemotherapy caused less frequent occurrence of the residual tumours than chemotherapy alone (48% and 20%, respectively, p = 0.026). The rate of brain metastases was significantly higher in pts given chemotherapy than in pts treated with chemotherapy and chest irradiation or chemotherapy and curative brain irradiation (90%, 67% and 36% of 50 cases, respectively). Distant metastases were distributed in the same pattern in both studied groups. The distribution of metastases was not dependent on the disease extent at the time of diagnosis.