Biomedical subjects

A Wallin

Publications and source records attributed to A Wallin.

At least 181 records · Page 10Linked to original sources

PubMedDate not supplied

Frontotemporal dementia can be distinguished from Alzheimer's disease and subcortical white matter dementia by an anterior-to-posterior rCBF-SPET ratio.

Sixteen patients with frontotemporal dementia (FTD), 27 with early-onset Alzheimer's disease, 25 with late-onset Alzheimer's disease, 19 with subcortical white matter dementia (SWD) and 28 normal controls underwent semiquantitative regional cerebral blood flow measurement (rCBF) using single-photon emission tomography (SPET; (99m)Tc-HMPAO) and either computerized tomography (CT) or magnetic resonance imaging (MRI) of the brain. An anterior-to-posterior rCBF-SPET ratio (mesial superior frontal gyrus/medial temporal lobes) was calculated, which significantly separated the FTD group from the other dementia groups and controls with a sensitivity of 87.5% and a specificity of at least 78.6%. CT/MRI was found to be helpful in the differential diagnosis between FTD and SWD. In FTD patients, the mesial superior frontal gyrus, near the polus frontalis, was found to be the region with the most reduced rCBF values.

Aged↗

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Intrathecal release of nitric oxide in Alzheimer's disease and vascular dementia.

A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of brain damage in dementia. We have recently demonstrated that patients with Alzheimer's disease (AD) and vascular dementia (VaD) display an intrathecal production of proinflammatory cytokines. TNF-alpha, one of these cytokines, leads to the production of nitric oxide (NO), a potent inflammatory mediator, by induction of inducible NO synthase. The aim of the present study was to investigate the intrathecal levels of nitrate, one of the main metabolites of NO, and to relate its levels to the degree of intellectual impairment, in patients with AD and VaD. Twenty patients with early AD and 26 patients with VaD were analyzed with respect to cerebrospinal fluid levels of nitrate by gas chromatography/mass spectrometry. Interestingly, in patients with AD but not VaD, the intrathecal levels of nitrate were significantly and inversely correlated (r = -0.68, p = 0.002) to the degree of intellectual impairment. Our study demonstrates an inverse correlation between the intrathecal levels of nitrate and the degree of cognitive impairment in patients with AD, suggesting a neuroprotective effect of NO in AD.

Aged↗

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The cerebrospinal fluid levels of tau, growth-associated protein-43 and soluble amyloid precursor protein correlate in Alzheimer's disease, reflecting a common pathophysiological process.

Cerebrospinal fluid (CSF) levels of tau (total tau), growth-associated protein-43 (GAP-43), soluble amyloid precursor protein (sAPP; i.e. total sAPP), and beta-amyloid(42) (Abeta(42)) were studied in patients with frontotemporal dementia (FTD; n = 14), Alzheimer's disease (AD; n = 47) and vascular dementia (VAD; n = 16), and in age-matched controls (n = 12). CSF-tau was increased in AD compared to controls and FTD (p < 0.001 for both). CSF-GAP-43 was increased in AD compared to controls (p < 0.05), and both CSF-GAP-43 and CSF-sAPP were increased in AD compared to FTD (p < 0.01). Positive and highly significant correlations were found between CSF-tau and CSF-GAP-43 in all groups and between CSF-tau, CSF-GAP-43 and CSF-sAPP in AD. The correlations found may reflect a common pathophysiologic process such as axonal degeneration.

Aged↗

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Treatment of Alzheimer's disease with clioquinol.

As heavy metal ions may be implicated in the formation of senile plaques in Alzheimer-afflicted brains, treatment with clioquinol was tested in 20 patients with Alzheimer's disease. Clioquinol is a chelator that crosses the blood-brain barrier and has greater affinity for zinc and copper ions than for calcium and magnesium ions. Treatment was given for 21 days at doses of 20 mg/day to 10 patients and 80 mg/day to another 10 patients. The study was blind to the dosages but included no controls. Cerebrospinal fluid (CSF) investigations revealed a significant increase at day 7 and a decrease at day 21 in Tau protein and growth-associated protein (GAP43). These proteins are increased in Alzheimer's disease and considered as rather stable markers. The initial increase may indicate a temporary cytotoxicity to the brain and/or an increased release into the CSF from stores in the tissue, possibly from senile plaques where the proteins are accumulated. The levels of CSF-Tau protein correlated positively and significantly with the serum levels of copper and also with the serum copper/zinc ratio. Clinical ratings showed slight improvement after 3 weeks treatment with clioquinol in this open study.

Aged↗

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Intracerebroventricular administration of GM1 ganglioside to presenile Alzheimer patients.

We have conducted a preliminary study of the optimum conditions for a therapeutic effect of ganglioside GM1 in Alzheimer's disease. Five patients with the early onset form of Alzheimer's disease (AD type I) received the ganglioside by intracerebroventricular administration for 12 months. Bilateral stereotactic punction of the frontal horns of the ventricular system was performed, and shunt catheters were implanted and connected to a programmable pump. The optimum GM1 dose varied between 20 and 30 mg/24 h. Neurological neuropsychological, psychiatric and neurochemical examinations were performed 7 days before surgery and on days 30, 90, 180 and 360. No patient found the surgery difficult and no patient or relative regretted that they participated in the study. The patients became more active and safer in relation to others and to performance of various activities from day 90. The cerebrospinal fluid level of the monoamine metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased.

Aged↗

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The neurochemistry of vascular dementia.

Vascular dementia (VAD) is cognitive impairment caused by changes in the blood circulation of the brain. It is not synonymous with multi-infarct dementia. The latter is a subgroup of VAD. Neurochemical investigations of noninfarcted brain tissue from patients with VAD show general changes in VAD brains. The serotonin metabolism is severely reduced and so is the activity of choline acetyltransferase. Monamine oxidase B is significantly increased in the white matter. A severe decrease in myelin components indicates white matter disturbances of such a degree that they must be considered to be of pathogenetic importance. The levels of some neuropeptides in the hypothalamus are increased. This is a finding which is in agreement with clinical findings of a high activity in the hypothalamic-pituitary-adrenal axis in patients with VAD. This high activity is possibly due to a loss of serotonergic inhibitory tone on the hypothalamus in VAD brains.

Brain↗

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The clinical diagnosis of vascular dementia.

The question was addressed whether the three vascular dementia (VAD) subtypes, multi-infarct dementia (MID), strategic-infarct dementia (SID), and subcortical white matter dementia (SWMD) fulfil the basic criteria for a disease: does a distinct pattern of clinical features match a distinct pathological picture for the various VAD subtypes? No obvious correspondence between structural pathological changes and symptoms or signs was found in the MID and SID subtypes. Therefore, the disease status of these VAD subtypes can be questioned. The VAD subtype SWMD, however, appeared to fulfil the basic criteria for a disease, as the subcortical white matter changes corresponded to the subcortical symptom pattern, with mental slowness, extrapyramidal and bilateral pyramidal deficits.

Brain↗

PubMedDate not supplied

Relationship between mental impairment and HPA axis activity in dementia disorders.

In 40 patients with Alzheimer's disease (AD, < 65 years), 56 patients with senile dementia of the Alzheimer type (SDAT, > or = 65 years) and 45 patients with vascular dementia (VAD), basal cortisol levels were estimated and the dexamethasone test (DST) was performed. The degree of dementia was assessed according to DSM-III-R and the GBS scale was used for quantitative measures of functional impairment. There were no significant differences in basal cortisol levels. Especially in the VAD group, scores on functional impairment correlated significantly with post-DST cortisol levels. The results indicate hypothalamic overactivity in demented patients which can be correlated to the degree of dementia. In VAD, and to a certain extent also in SDAT, there appears to be a disconnection between cortical areas, including the hippocampus and the hypothalamus.

Aged↗

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Glial fibrillary acidic protein in the cerebrospinal fluid of patients with dementia.

Glial fibrillary acidic protein (GFAP) is the structural protein of the astroglial intermediate filament that forms the morphological basis of astrogliosis. In the present study, GFAP concentrations in cerebrospinal fluid were measured in patients with various dementia diseases. A significant correlation between GFAP and age was found both in the total dementia group and in the controls. Covariance analysis with GFAP as dependent variable and age and albumin ratio as covariates followed by multiple group comparisons showed that, with regard to GFAP levels, the controls (n = 39) differed significantly from the patients with vascular dementia (n = 20; p < 0.05), senile dementia of the Alzheimer type (n = 29; p < 0.05), and 'pure' Alzheimer's disease (n = 8; p < 0.05), but not from those with frontal lobe dementia (n = 5).

Adult↗

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Apolipoprotein E in cerebrospinal fluid from patients with Alzheimer's disease and other forms of dementia is reduced but without any correlation to the apoE4 isoform.

Apolipoprotein E (apoE) has been suggested to play a role in regenerative processes in the brain after trauma, and also in the pathogenesis of Alzheimer's disease (AD). We examined cerebrospinal fluid (CSF) apoE in a material consisting of 23 patients with early-onset AD (EAD), 31 with late-onset AD (LAD), 16 with frontal-lobe dementia (FLD), 25 with vascular dementia (VAD) and 25 controls. CSF-apoE was decreased in all of EAD (1.8 +/- 1.1 mg/l; p < 0.0005), LAD (2.5 +/- 0.9 mg/l; p < 0.0005), VAD (2.3 +/- 1.4 mg/l; P < 0.0005) and FLD (3.0 +/- 1.3 mg/l; p < 0.05) compared to the control group (5.7 +/- 4.0 mg/l). Since apoE4 has been found to bind to beta/A4-amyloid, and AD patients homozygous for apoE4 to have higher number of senile plaques than apoE3 homozygotes, we also examined the relation between CSF-apoE and apoE alleles. However, CSF-apoE did not significantly differ between patients with different apoE isoforms. Our findings support that apoE is involved in the pathogenesis of dementia disorders, both degenerative and vascular, but the CSF-apoE level is not influenced by the apoE isoforms. CSF-apoE may be used as an unspecific marker for neurodegenerative disorders, but not in purpose of differential diagnostics between different dementia disorders.

Age of Onset↗

PubMedDate not supplied

Sleep-related breathing and movement disorders in healthy elderly and demented subjects.

Reported findings regarding sleep and sleep disorders in the elderly often conflict. Differences in results across studies may arise from selection of subjects, definitions and recording conditions. Our purpose was to test a method to study elderly, both healthy and demented, under the most natural conditions, without disturbing a fragile sleep. Using clinical parameters and a non-disturbing recording method, we evaluated sleep quality in patients with carefully diagnosed dementia and compared the results to a group of healthy subjects between 50 and 70 years of age. Healthy subjects awoke less and had more quiet sleep than patients, while in patients a tendency for delayed sleep latency and more active sleep was observed. Consistent with previous investigations, sleep-related respiratory disorders (SRRD) were more common in patients than in the matched control group, and periodic breathing appeared only among patients. SRRD, of both obstructive and central types, were only mild, with periodic breathing dominating only among patients. Most of the desaturations were less than 10%. We did not observe respiration of the Cheyne-Stokes type. Patients had more sleep-related movement disorders (SRMD), particularly with increase of twitches and long movements. Periodic movements were not significantly increased among the patients. The method, and the data obtained may be useful for practitioners dealing with sleep disorders in geriatric populations. In the elderly, interactivity between sleep, SRRD and SRMD may be bidirectional and as elderly and demented subjects might have a distorted homeostatic sleep response, SRRD and SRMD, even in a mild form, may cause sleep disruption and worsen dementia.

Aged↗

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Diagnosis of dementias using partial least squares discriminant analysis.

Twenty patients with Alzheimer's disease (AD), 34 with senile dementia of the Alzheimer type (SDAT) and 12 with vascular dementia (VAD) were carefully investigated. The diagnoses were made according to the DSM-III-R criteria and for AD/SDAT also according to the NINCDS-ADRDA criteria. The data set consisted of 29 descriptor variables obtained at the examination, and the data were fitted to a partial least squares model using dummy variables for the response variables (i.e. clinical diagnoses). The distribution of the scores over the descriptor variable space revealed adequate classification regarding all three diagnoses, with some overlap between SDAT and AD and between VAD and SDAT. The study demonstrates a clear difference in symptomatology between AD and SDAT with no influence of age per se or the severity of dementia.

Aged↗

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Chromogranin A in cerebrospinal fluid: a biochemical marker for synaptic degeneration in Alzheimer's disease?

Biochemical markers for AD would be of great value both to improve the clinical diagnostic accuracy in scientific studies and to increase the knowledge of the pathogenesis of the disorder. One of the main features of AD is a degeneration of synapses. Therefore, we examined if chromogranin A (CrA), the major protein of large dense-core synaptic vesicles, in cerebrospinal fluid (CSF) may be of value as a biochemical marker for the synaptic function in AD. The mean concentration of CrA in CSF was about 7.5 times higher than its concentration in serum, and there was no significant correlation between CSF-CrA and the blood-brain barrier function (measured as the CSF/serum albumin ratio), nor between CSF-CrA and serum-CrA. These findings suggest that the major portion of CSF-CrA is locally produced within the CNS. There were no significant differences in CSF-CrA between the AD (n = 29), vascular dementia (n = 13), and age-matched control (n = 9) groups (99.9 +/- 58.9 ng/ml, 108.0 +/- 69.4 ng/ml, and 115.1 +/- 44.4 ng/ml, respectively). However, when the AD group was subdivided into AD type I (n = 12) and AD type II (n = 17), a lower concentration of CSF-CrA was found in AD type I (72.8 +/- 28.9 ng/ml) compared with controls (115.1 +/- 44.4 ng/ml), p < 0.02, and compared with AD type II (119.1 +/- 67.5 ng/ml), p < 0.05, while CSF-CrA did not significantly differ between AD type II and controls. These findings suggest that CSF-CrA has a potential as a biochemical marker for the synaptic degeneration in AD type I, and gives further support for the relevance of identifying the AD type I (pure AD) subgroup in scientific studies.

Aged↗

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EEG findings in dementia are related to the parietal lobe syndrome.

EEG indicators were correlated with clinical items in 174 patients with dementia diagnoses based on the DSM-III-R criteria. The patients' clinical symptomatologies were presented as regional brain syndromes, i.e. parietal lobe, frontal lobe, subcortical and global (nonregional) syndromes. The EEGs were abnormal in 87% of the cases. The typical abnormalities consisted of diffusely distributed slow wave activity. A significant correlation was found between the degree of slow wave abnormality and the degree of dementia. The results of the statistical analysis also suggest that EEG slow wave activity in dementia primarily reflects parietal lobe dysfunction. No association seems to exist between EEG slow wave activity and frontal lobe dysfunction.

Aged↗

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Clinical heterogeneity of probable Alzheimer's disease.

When the symptomatology in probable Alzheimer's disease (AD) was studied, two subgroups emerged: one with predominant cortical symptoms of parietal type (AD type I) and another with general cognitive symptoms but absence of or only mild cortical symptoms (AD type II). In AD type I, the age at onset was significantly lower, confusional symptoms and leukoariosis on computerized tomographic scan were less frequent, and the ganglioside GM1 concentration in cerebrospinal fluid was significantly higher than in AD type II. Although the significance of changes in cerebrospinal fluid gangliosides has not been fully elucidated, it is possible that the increase in cerebrospinal fluid GM1 reflects a more severe degeneration of neurons and synapses in AD type I than in AD type II. The relation between symptomatology and leukoariosis suggests that leukoariosis has clinical significance in AD patients. The total results suggest heterogeneity of probable AD. AD type I appears to constitute a classic AD subgroup with memory disturbances and marked cortical symptoms of parietal type, while age-related changes, vascular changes, and leukoariosis may be responsible for the more generalized symptomatology in AD type II.

Aged↗

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Limited role of the intestinal microflora in the nephrotoxicity of hexachloro-1,3-butadiene in rats.

The nephrotoxicity of hexachlorobutadiene has been investigated in germ-free rats and compared to conventional rats that have a normal intestinal microflora. Presynthesized mercapturate intermediates of hexachlorobutadiene, the glutathione and the cysteine S-conjugate, were also administered. Germ-free rats appeared to be slightly more susceptible to hexachlorobutadiene by judging the extent of morphological changes compared to conventional ones. A similar response was also observed after treatment with the glutathione and cysteine S-conjugates. However, no significant difference between germ-free and conventional animals was monitored in the extent of elevation of blood urea nitrogen and plasma creatinine after treatment with hexachlorobutadiene or the glutathione and the cysteine S-conjugates. The urinary excretion of marker enzymes was monitored and showed that gamma-glutamyl transferase was significantly more increased in the germ-free rats when treated with the cysteine S-conjugate. In addition, no difference in the rate of glutathione conjugation of hexachlorobutadiene was measured between the two groups. Although a tendency toward a protective effect by the presence of an intestinal microflora was observed, the role of the intestinal microflora in detoxifying hexachlorobutadiene seems to be of limited importance in rats.

Animals↗

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Heterogeneity of vascular dementia: mechanisms and subgroups.

Today, multiple, thromboembolically generated cerebral infarcts are regarded as the main pathogenetic pathway of vascular dementia (VAD), with multi-infarct dementia (MID) as its clinical counterpart. However, taking into account other vascular mechanisms that may influence the brain, such as vessel-wall damage (atherosclerosis, hyalinosis, amyloid angiopathy, or blood-brain barrier dysfunction), cerebrovascular insufficiency (disturbance of systemic circulation, perfusion vulnerability related to the vascular anatomy of the brain, or disturbance of autoregulation), and hyperviscosity, it is evident that MID is not the only VAD category. The diagnosis of MID ought to be reserved for the combination of progressive dementia associated with cerebral ischemic events and evidence of infarction that is mainly associated with the large cerebral arteries. Subcortical white-matter dementia characterized by frontosubcortical symptomatology, white-matter lesions, and small-vessel involvement with or without lacunes/infarcts--a combination of lacunar dementia and Binswanger's disease--appears to be another important VAD disease.

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Role of white matter lesions in cognitive impairment of vascular origin.

White matter changes are detected with high frequency by neuroimaging techniques in aged subjects with cerebrovascular risk factors or diseases and in cognitively impaired patients. Their direct role in causing cognitive deterioration has not been established, although their frequency is higher in demented subjects than in normal controls, and they are associated with specific cognitive deficits, particularly those related to impairment of frontal lobe functions. The aim of this paper is to critically review the existing knowledge about the role of white matter lesions in cognitive impairment of vascular origin. After reviewing the scarce evidence and the numerous clues suggesting a possible role of white matter lesions in causing mental decline, proposals are advanced about elements that could be a basis for revised criteria for vascular dementia for clinical trials. Finally, some items requiring future joint investigations in the fields of age-related white matter lesions are identified.

Cerebrovascular Disorders↗