Correlation between cognitive brain function and electrical brain activity in dementia of Alzheimer type

Enterocytes were detached from various parts of the digestive tract of chickens by treatment with DTT or with hyaluronidase. Isolated enterocytes were exposed to suspensions of the V4 strain of Newcastle disease virus (NDV). Removal of virus from the supernatant fluid was taken as evidence of binding of virus to enterocytes and residual virus was measured both by infectivity assay and by ELISA. Enterocytes from duodenum, jejunum, ileum, caecum, and rectum bound the virus; enterocytes from oesophagus, crop and proventriculus did not.     

Decreased lumbar cerebrospinal fluid levels of monoamine metabolites in vascular dementia

The levels of the monoamine metabolites 5-hydroxy-indoleacetic acid (5-HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxy-phenylglycol (HMPG) were determined in lumbar cerebrospinal fluid (CSF) of 56 patients with vascular dementia (VAD) and 57 healthy controls. Despite CSF sampling under standardized conditions, the variability in values was wide among both patients and controls. This suggests that yet unknown factors affect the lumbar CSF concentrations of monoamine metabolites. The VAD group showed significantly lower mean concentrations of 5-HIAA (p < .001) and HVA (p < .001) than the control group. These low concentrations appear to be no disease-specific phenomenon, but may be attributable to subcortical white-matter changes or a decreased production of monoamines, which are dependent on oxygen for their synthesis.     

Crystallized and fluid intelligence in elderly patients with mild dementia of the Alzheimer type

OBJECTIVE: To describe a systematic procedure for adapting, or 'tailoring' the World Health Organisation's 'global guidelines for the management of HIV/AIDS in adults and children' for use in two developing countries: Malawi and Barbados. DESIGN: In order for these guidelines to achieve reproducibility, clinical flexibility, and clinical applicability, a systematic procedure is needed to tailor the guidelines to the local practice conditions of specific settings. METHODS: A group of local experts in each country used a nominal group process to modify the global program on AIDS (GPA) guidelines for local use. Semantic analysis techniques, known as clinical algorithm nosology (CAN), were used to compare the two modified guidelines with the global ones to determine the extent and type of differences between sets of guidelines. RESULTS: Standard, locally-tailored algorithm map guidelines (AMG) were developed within 4 months. CAN semantic analysis showed that guideline structure was maintained; 572/858 (66.6%) decision nodes were found to be the same in the GPA/Malawi, GPA/Barbados and Malawi/Barbados comparisons. However, different guideline versions managed patients quite differently, as evidenced by clinical algorithm patient abstraction (CAPA) scores of between 0 and 8.46 (0 = different; 8 = similar; 10 = identical). Analysis of the 197 specific differences found in these abstractions showed that 83% were in approaches to diagnosis and therapy, while the remaining 17% related to disease prevalence. CONCLUSIONS: Standard techniques involving consensus used to develop clinical guidelines can also be employed to tailor these guidelines to local settings. Semantic analysis shows that the tailoring preserves structure but may involve significant modification to the processes of clinical care that could in turn affect care outcomes.     

Processing of neuropeptide Y and somatostatin in human cerebrospinal fluid as monitored by radioimmunoassay and mass spectrometry

The processing of four neuropeptides, neuropeptide Y (NPY) 1-36, NPY (18-36), somatostatin (SOM) 1-28, and SOM (15-28) was studied in human cerebrospinal fluid (CSF) by using a novel combination of methods that included radioimmunoassay (RIA) and mass spectrometry. Untreated CSF samples were chromatographed using reversed-phase high pressure liquid chromatography (RP-HPLC) followed by NPY-RIA or SOM-RIA. These results were compared with those obtained by incubating CSF with exogenous synthetic peptides and directly detecting peptide fragments by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-MS). Using this combination of methods, we were able to determine the probable identities of peptides/peptide fragments recognized in radioimmunoassays. The most important NPY-immunoreactive components in CSF were found to be NPY (1-36) and NPY (3-36). Metabolic products of SOM (15-28) were found to contribute to SOM-like immunoreactivity (SOM-LI) in CSF, but SOM (1-28) only to a lesser degree. Differences in the rate of neuropeptide processing were observed. These differences depended more on the length of the peptide than its sequence. NPY (18-36) and SOM (15-28) were rapidly and extensively processed, whereas NPV (1-36) and SOM (1-28) were processed much more slowly in CSF. The production of SOM (15-28) from SOM (1-28) by enzymes in CSF was not observed. Also, the presence of a disulfide bond in the somatostatins appeared to stabilize them against enzymatic digestion of the ring structure. The results detailed in this report confirm MALDI-MS important role in studies of neuropeptide processing in CSF.     

Acetylcholine in human CSF: methodological considerations and levels in dementia of Alzheimer type

Four different methods to measure acetylcholine (ACh) and choline (Ch) concentration, i.e. thermospray/mass spectroscopy (TS/MS), high pressure liquid chromatography/mass spectroscopy (HPLC/MS), high pressure liquid chromatography/electrochemical detection (HPLC/ECD) and gas chromatography/mass spectroscopy (GC/MS), both latter methods coupled to a solid phase extraction system were compared for their applicability to human lumbar cerebrospinal fluid (CSF). Furthermore, samples from 15 control persons and 11 patients with dementia of Alzheimer-type (DAT) were compared to search for an ACh deficit in the CSF in DAT. GC/MS was the most sensitive, but most laborious method, and HPLC/ECD was acceptably sensitive, reliable and more specific. TS/MS was not specific enough for CSF extracts and HPLC/MS was more specific, but far less sensitive. Thus, only GC/MS and HPLC/ECD were qualified to detect ACh in human CSF extracts. Comparison of GC/MS and HPLC/ECD revealed highly correlated levels of ACh (r = 0.999). Using HPLC/ECD, ACh concentrations were greatly reduced in the DAT group (3.75 +/- 1.40 pmol/ml CSF) as compared to the controls (6.14 +/- 1.39 pmol/ml CSF), but the difference between controls and DAT patients was not statistically significant due to the number of samples below detection limit (8 out of 11 samples in DAT, 7 out of 15 in controls). Ch concentrations were not statistically significant between the two groups. The data show that methodological limitations preclude a widespread clinical application of determining ACh in the human CSF. Despite of reductions of ACh in the CSF in DAT, the determination of Ach in the CSF is not suitable for diagnostic purposes.     

High cerebrospinal fluid tau and low amyloid beta42 levels in the clinical diagnosis of Alzheimer disease and relation to apolipoprotein E genotype

Methods for selective alkylation of chalcones in the alpha- or beta-position and for selective reduction of the alpha,beta-double bond have been developed. The antiparasitic potencies of the alpha,beta-double bond modified chalcones only differ marginally from the potencies of the parent chalcones indicating that the propenone residue only functions as a spacer between the two benzene rings, which are the true pharmacophore.     

Zinc deficiency increases hypothalamic neuropeptide Y and neuropeptide Y mRNA levels and does not block neuropeptide Y-induced feeding in rats

Zinc deficiency reduces intake and produces an unusual approximately 3.5-d cycle of intake in rats. The mechanism underlying the anorexia and cycling has not yet been defined; current hypotheses suggest that alterations in amino acid metabolism and neurotransmitter concentrations may be a part of this anorexia. Recent reports indicate that appetite-stimulating neuropeptide Y (NPY) may be elevated during zinc deficiency. This suggests that a resistance to NPY may exist during zinc deficiency because NPY levels are high, yet appetite is low. The purpose of this study was to measure NPY peptide and mRNA concentrations during zinc deficiency in specific nuclei of the hypothalamus in which peptide and mRNA for NPY are known to be associated with appetite, and also to determine whether zinc-deficient rats are responsive to central infusions of NPY. Both NPY peptide levels in the paraventricular nucleus and NPY mRNA levels in the arcuate nucleus were higher (P < 0.05) in zinc-deficient rats than in zinc-adequate rats. When rats were administered exogenous NPY to the paraventricular nucleus, both zinc-deficient and zinc-adequate rats responded similarly by increasing food intake. These results suggest that NPY is elevated during zinc deficiency in an attempt to restore normal food intake levels, rather than being reduced and thereby contributing to the anorexia associated with zinc deficiency. During zinc deficiency, NPY receptors are able to bind NPY and initiate an orexigenic response.     

Serial position effects in dementia of the Alzheimer type

We evaluated the usefulness of an automated hematology analyzer (SE-9000) for the identification and counting of peripheral blood stem cells (PBSCs). The samples tested were from 14 patients with hematological malignancies. Peripheral blood samples were collected from the subjects before and after a course of chemotherapy. From the leukapheresis sample, CD34+ cells, assumed to be hematopoietic stem cells, were obtained with an immunomagnetic cell separator. The CD34+ cells obtained accumulated in the gate corresponding to low recurrent frequencies of the automated hematology analyzer. This gate shows results of the 'immature information' (IMI) channel. Software for detection of only the cells that accumulated in this gate was therefore developed. With this trial program, the regression coefficient between the percentage of leukocytes from the blood samples that were CD34+ and the percentage of such leukocytes that appeared on the IMI channel was 0.79. With this analyzer, the number of PBSC could be counted in about 80 s. The identification and counting of cells picked up by the IMI channel should be clinically useful for the monitoring of changes in PBSC after chemotherapy for mobilization.     

Preserved cognitive skills in dementia of the Alzheimer type

OBJECTIVE: To describe preserved cognitive skills in patients with dementia. DESIGN: Case series. SETTING: Community clinic. PATIENTS: Five patients who met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease and were claimed to retain a cognitive skill. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Standard neuropsychological tests and individualized measures of patient's skilled behaviors. For patients who remained skilled at games, performance was compared with that of normal controls in direct competition. For the patient-trombonist, raters compared premorbid and postmorbid recordings of his play. RESULTS: One patient continued to play the trombone in a Dixieland band, although he could not name well-known numbers that he played. Another continued to solve adult jigsaw puzzles. A third patient retained skill at canasta, the fourth at dominoes. The fifth patient remained a skillful contract bridge player, although he could not name the suits or articulate simple bidding rules. Four patients had impaired performance on standard anterograde and remote memory and naming tests but performed normally on pursuit rotor and letter fluency tests. Mini-Mental State Examination scores for these patients ranged from 10 to 22. One patient refused neuropsychological testing but displayed his skill. CONCLUSIONS: Together with previous studies of preserved piano playing or painting skills, our findings indicate that a broad range of complex cognitive abilities may be preserved in patients with dementia of the Alzheimer type who cannot perform simpler actions.     

Neurobiology and clinical aspects of neuropeptide Y

Although a large and still increasing number of neuroactive peptides have been discovered in the mammalian brain over the years, it has been difficult to link most of these molecules with specific brain functions and/or brain diseases. A lack of pharmacological tools has hampered the study of brain peptide systems and the elucidation of which among these systems have retained important physiological functions through phylogenesis. Neuropeptide Y (NPY) is one the most abundant neuropeptides in the mammalian brain. A combination of basic and clinical studies has made it possible to circumvent some of these difficulties and provides evidence for a role of NPY in the control of endocrine hypothalamic and pituitary functions, in hypothalamic control of food intake and circadian rhythm, and in limbic emotional integration. Of particular interest is NPY's unique action as an endogenous anxiolytic and its possible role in clinical states of anxiety and depression. Here, we review the biology, anatomy, and physiology of central NPY systems and studies of these systems in various disease states.     

Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain

Cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA levels were measured with the Nucleic Acid Sequence-Based Amplification (NASBA) assay to determine the relationship with neurological status; 37 subjects with HIV dementia (HIV-D) were compared with 77 with HIV with minor neurological signs (HIV-MCMD) and 93 neurologically normal HIV-seropositive individuals (HIV-NML). The NASBA assay had a lower limit of detection of 100 copies per milliliter. Mean CSF log HIV RNA levels were significantly higher in those with dementia after adjusting for CD4 count and were correlated with dementia severity. Plasma levels did not distinguish comparably immunosuppressed subjects with or without dementia. CSF and plasma RNA levels were significantly intercorrelated for subjects with CD4 counts <200/mm3 and also correlated inversely with CSF beta2-microglobulin. CSF RNA levels were independent of CSF pleocytosis or antiretroviral exposure. Brain RNA levels were consistently higher than CSF but correlated with CSF values for dementia subjects. The NASBA assay can be used reliably to determine HIV RNA levels in CSF, brain, and plasma samples. CSF HIV RNA may be a surrogate marker for brain infection, based on the observed correlation with brain levels. The association between plasma HIV RNA and CSF levels of HIV and beta2-microglobulin suggests that both viral load and CNS immune activation are important determinants of neurological disease.     

Neurosyphilis and penicillin levels in cerebrospinal fluid

Because neurosyphilis may progress despite therapy with the recommended penicillin regimens, 15 subjects with positive tests for syphilis in the serum and cerebrospinal fluid (CSF) were studied. All of these patients had CSF pleocytosis. Two received penicillin G (5 and 10 million units per day intravenously, respectively) and 13 received benzathine penicillin G, 3.6 million units per week intramuscularly; treatment lasted four weeks. During intravenous and after intramuscular penicillin therapy, a spinal tap was performed on all subjects; later, assays were done. Of two patients who received intravenous penicillin G, one had 0.3 mug/ml and the other had 2.4 mug/ml penicillin in the CSF. Twelve of 13 patients who received benzathine penicillin G had no detectable penicillin in the CSF; one patient had 0.1 mug/ml penicillin in the CSF.     

Focal cognitive deficits in dementia of the Alzheimer type.

It is widely accepted that the natural history of Alzheimer type-dementia is accurately described by a relatively fixed, invariant sequence of stages of behavioral, cognitive, and neurological symptoms. This stage-wise deterioration model is examined and found wanting. The evidence shows that there is no generalization about the inevitable ordering of symptoms that has not been contradicted by reports in the literature. Two alternatives to the stage-wise model are discussed, both of which reject the notion of a homogeneous disintegration of function and take as a goal the delimitation of a set of symptom domains that define and differentiate patients. Of these 2 alternatives, the subgroups model and the multiple components model, the latter seems to accord best with the available data. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Autonomic dysfunction in patients with dementia of the Alzheimer type

Abnormalities of the noradrenergic system have been documented in the central nervous system of patients with dementia of the Alzheimer's type (DAT). To evaluate the autonomic sympathetic system in DAT, we measured lying and standing blood pressure (BP), pulse, and plasma epinephrine (E) and norepinephrine (NE) in 60 DAT patients (mean age +/- SD = 65 +/- 8 years), and 20 normal elderly controls. DAT patients had normal baseline findings (BP, pulse, NE, and E). Upon standing, plasma NE and E significantly increased in both DAT patients and controls, without group differences. However, the systolic BP response to standing was reduced in DAT patients compared with the normal controls (repeated measures ANOVA, p < 0.01). This impaired response of the systolic BP on standing was particularly evident in DAT patients with symptoms of depression. Severely impaired DAT patients did not differ in E, NE, BP, pulse, or in orthostatic changes from mild-to-moderately impaired patients. These results suggest that the sympathetic response to the stress of standing is functionally impaired in DAT. This deficit was especially evident when DAT was accompanied by depression, consistent with prior studies in non-demented depressed patients.     

Amygdala-hippocampal atrophy and memory performance in dementia of Alzheimer type

The aim of the present study was to examine the involvement of brain structures, especially the amygdala-hippocampal complex, in dementia of Alzheimer type (DAT), and to assess the relation of amygdala-hippocampal atrophy with memory dysfunction. 14 patients with DAT and 10 healthy age-matched controls were examined with different neuropsychologic tests including the UCLA-Auditory Verbal Learning Test. MRI was performed with a conventional 1.5-tesla scanner. Atrophy was found in many brain structures of demented subjects in comparison with healthy age-matched controls. The volumes of amygdala-hippocampal complexes and of the temporal lobes of demented subjects were more reduced than the total brain volume and other structures. Memory dysfunction was highly correlated with atrophy of the amygdala-hippocampal complexes and of the temporal lobes. Consequently, DAT seems to affect the amygdala-hippocampal complex and their related function (i.e. memory) more than other cerebral structures, but cerebral degeneration in DAT is not restricted to these structures.     

Effects of hyperglycemia on memory and hormone levels in dementia of the Alzheimer type: A longitudinal study.

The effect of hyperglycemia on hormone levels, metabolite levels, and memory performance was examined in 22 Ss with very mild and mild probable dementia of the Alzheimer type (DAT) and in 12 normal elderly adults. Ss were tested in 3 plasma glucose conditions (fasting baseline, 175 mg/dl, and 225 mg/dl) at initial and 18-mo follow-up sessions. Initially, adults with very mild DAT showed memory facilitation and elevations in plasma insulin in the 225-mg/dl glucose condition relative to baseline. At follow-up, very mild DAT patients whose dementia had progressed showed significant decreases in insulin and hyperglycemic memory facilitation. Changes in basal insulin and cortisol levels over time were correlated with memory changes for DAT Ss. These results suggest that glucoregulatory abnormalities may contribute to the pathophysiology of DAT. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bender-Gestalt Test performance in senile dementia of the Alzheimer type.

Bender-Gestalt Test performances of 144 persons with very mild, mild, or moderate senile dementia of the Alzheimer type (SDAT) and 96 healthy older adults ranging in age from 63 to 95 yrs were compared. Total scores and error types according to the modified Hutt-Briskin scoring system are reported. The Bender-Gestalt Test does not appear to be useful in differentiating very mild or mild SDAT from normal aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preclinical cognitive markers of dementia of the Alzheimer type.

56 nondemented elderly normal control (NC) Ss were studied at 3 consecutive annual administrations of the California Verbal Learning Test (CVLT). NC Ss with a positive family history for progressive dementia performed significantly worse than individuals with a negative family history for progressive dementia on several quantitative and qualitative indices of the CVLT and were more likely to undergo changes in diagnostic status over time (i.e., develop dementia of the Alzheimer type [DAT]). Stepwise discriminant function analyses of critical CVLT indices of the NC Ss and of 25 patients with mild DAT classified 5 NC Ss as DAT patients 1–2 yrs prior to their eventual changes in diagnostic status. Results suggest that specific memory deficits may serve as preclinical cognitive markers for DAT, especially in individuals with risk factors for DAT such as a positive family history. (PsycINFO Database Record (c) 2010 APA, all rights reserved)