Effects of acupuncture on glycometabolic enzymes in multi-infarct dementia rats.

Acupuncture has exhibited therapeutic effects on vascular dementia in our previous research. The mechanism of its anti-dementia effects involves energy metabolism. For brain cells, glucose metabolism is almost the only source of energy, and glucose metabolism disorders are early signs of dementia. In addition, glucose metabolism associates closely with glycometabolic enzymes, thereby maintains normal energy supply in brains and neurological and mental activities. In order to investigate its anti-dementia mechanism, we studied the effects of acupuncture on behavior of multi-infarct dementia (MID) rats and glycometabolic enzymes protein expression and activities in their brains. Results showed acupuncture improved the cognitive disorder, and increased the activities of hexokinase, pyruvate kinase, and glucose 6 phosphate dehydrogenase. Accordingly, it suggests that the anti-dementia effects of acupuncture may be mediated by up regulation of hexokinase, pyruvate kinase, and glucose 6 phosphate dehydrogenase activities, influencing energy metabolic system and thus overcoming the dysfunctional cognition of MID.

Overexpression of semicarbazide sensitive amine oxidase in the cerebral blood vessels in patients with Alzheimer's disease and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Semicarbazide sensitive amine oxidase (SSAO) metabolizes oxidative deamination of primary aromatic and aliphatic amines, and, in the brain, it is selectively expressed in blood vessels. SSAO expression is examined, by immunohistochemistry with a purified polyclonal antibody to SSAO from bovine lung, in the brains of subjects with Alzheimer disease (AD; n=10), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL; n=2), and age-matched controls (n=8). SSAO immunoreactivity is restricted to meningeal and parenchymal blood vessels in control and diseased brains. Yet, a marked and selective increase in SSAO immunoreactivity occurs in association with betaA4 vascular amyloid deposits in patients with AD, and in the vicinity of the typical granular deposits in the blood vessels of gray and white matter in patients with CADASIL. Oxidative deamination of primary aromatic and aliphatic amines by SSAO produces ammonia, hydrogen peroxide and the corresponding aldehyde. Moreover, increased SSAO immunoreactivity is associated with increased Cu/Zn superoxide dismutase 1 expression restricted to abnormal blood vessels in diseased brains. Therefore, it is suggested that increased SSAO expression is a source of oxidative stress in the blood vessel wall in AD and CADASIL.

[Neuro-specific enolase in acute ischemic stroke and related dementia patients].

Neuron-specific enolase (NSE) levels of cerebrospinal fluid (CSF) were measured in 39 patients with ischemic stroke and 15 controls. There was a significant increase of CSF NSE in patients with acute ischemic stroke as compared with the controls. The altered CSF NSE levels were well correlated with the infarct size in CT scan. The CSF NSE levels were higher in 6-patients who were diagnosed as multi-infarct dementia (MID) after 6-month follow-up than in 22 non-MID patients of this series. Our research supports the view that CSF NSE can be a useful biochemical marker for brain ischemia. The importance of CSF NSE for dementia related to ischemic stroke is worth further studying.

Neuron-specific enolase in patients with acute ischemic stroke and related dementia.

Neuron-specific enolase (NSE) levels of cerebrospinal fluid (CSF) were measured in 39 patients with ischemic stroke and 15 controls. There was a significant increase of CSF NSE in acute ischemic stroke patients as compared with the controls. The altered CSF NSE levels correlated well with the infarct size in CT scan. The CSF NSE levels were higher in 6-multiinfarct dementia (MID) patients who were diagnosed after 6-month follow-up than those in 22 non-MID patients of this series. Our research supports the view that CSF NSE can be a useful biochemical marker for brain ischemia. The importance of CSF NSE in the study of dementia related to ischemic stroke is worth further studies.

Cerebrospinal fluid of patients with senile dementia of Alzheimer's type shows an increased inhibition of alpha-chymotrypsin.

The inhibition of alpha-chymotrypsin induced by cerebrospinal fluid from patients with senile dementia of Alzheimer's type, vascular dementia, and nondemented controls was investigated. We optimized the sensitivity of the assay so that the inhibition of alpha-chymotrypsin could be measured in all samples. The competitive inhibition was proportional to the amount of cerebrospinal fluid (CSF) added to the reaction mixture. After correction for protein concentration, the inhibition was higher with CSF from patients with senile dementia of Alzheimer's type than with those from patients with vascular dementia or controls. Inhibitory activity appeared to be specific for alpha-chymotrypsin because no inhibition for papain was found. Moreover, the depletion of alpha 1-antichymotrypsin from CSF by immunoadsorption revealed that this serpin was responsible for the disappearance of the inhibitory activity. Our findings suggested that the increased alpha-chymotrypsin inhibitory activity might represent an in vivo functional index of an abnormal protease metabolism in patients with Alzheimer's disease.

CSF cholinesterase in early-onset and late-onset Alzheimer's disease and multi-infarct dementia of Chinese patients.

Using Ellman spectrophotometric method we measured the total cholinesterase (ChE) activity in lumbar cerebrospinal fluid (CSF) of 13 persons without neurological disorder, 10 non-demented patients with cerebral infarcts, 17 patients with dementia of Alzheimer's type (DAT) (11 presenile, 6 senile cases), 10 patients with multi-infarct dementia (MID), 1 patient with Parkinson's disease associated with dementia. The ChE activity in CSF was significantly lower in the DAT group compared with age-matched control subjects (p < 0.001). This paper also analyses the possibility of using CSF ChE activity as a marker of DAT, and the relationships between its level of activity and the age of the patient at onset, stage of illness and severity of dementia as well as discrepancies in the data published so far. Previous work has shown that ChE activity in the brain tissue and CSF of MID is normal: therefore, if low ChE activity is found in the CSF of MID patients, as was obtained in 8 out of 10 cases in our series, the diagnosis of mixed dementia should be considered.

CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters.

Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a subgroup of MID patients characterised by dilated ventricles and disturbed CSF hydrodynamics. These data suggest that a low CSF outflow conductance may facilitate the clearance of acidic substances from the arachnoid space at the probenecid sensitive active transport site. Alternative explanations would be that a pathologically low CSF outflow conductance is accompanied by an inverse caudorostral flow of CSF or a compromised trans-ependymal diffusion.

Platelet MAO-B activity and the psychopathology of Parkinson's disease, senile dementia and multi-infarct dementia.

Monoamine oxidase-B (MAO-B) activity of platelets of an age- and sex-matched group of controls was compared with several groups of inpatients having non-familial dementia of Alzheimer type (DAT), Parkinson's disease (PD), multi-infarct dementia (MID), mixed types of these 3 diseases and a group of other central nervous system (CNS) organic disorders. All patients were subjected to several psychometric tests, including the Sandoz Clinical Assessment--Geriatric Scale, Hamilton Rating Scale for Depression, Mini-Mental State Examination and the Organic mental Disorder Scale (OMDS). A statistically significant enhancement of MAO-B activity could be observed in DAT patients and in PD patients, whereas the MID group showed a mean activity similar to that of the control group and the group with other organic CNS disorders. In DAT patients the degree of dementia in the OMDS test and the enhancement of MAO activity were positively correlated, but PD did not show such a correlation. It is concluded that the increase of MAO activity in PD and in DAT might be due to a disease-related enhanced affinity to oxygen and to such oxygen-derived radicals as superoxide or hydroxyl radicals. However, a possible drug-induced enhancement of MAO activity in PD cannot be excluded. Furthermore, the MAO-B activity values in platelets of individual patients or controls are not indicative of diagnosis or prognosis of any of these diseases and are of no disease-related specificity.