CARDIOVASCULAR RISK FACTORS AS POTENTIAL MARKERS FOR MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE

Background: Mild cognitive impairment (MCI) is an early stage of cognitive decline that has a significant risk of converting to dementia. Cardiovascular pathology appears to have a major impact in cognitive decline, and it is clear that early identification and correction of cardiovascular morbidity could have a major impact on cognitive functioning. Subjects and methods: Our study was conducted in order to identify some cardiovascular risk factors among patients with cognitive decline (MCI or Alzheimer disease-AD) and to find if there is any correlation with the degree of cognitive decline. We evaluated the body mass index, total cholesterol, hypertension, history of smoking, alcohol consumption and diabetes mellitus in patients with MCI and AD, compared with an age-matched control group. Results: Regarding the body mass index, we observed a progressive decrease in patients with MCI and AD, in comparison with the control group. Similar aspects were also observed in the case of cholesterol levels, only that post hoc analysis revealed no significantly statistical differences between MCI and AD groups. The systolic blood pressure was increased in the patients with MCI and AD. Also, as in the case of cholesterol levels, post hoc analysis revealed no significantly statistical differences between MCI and AD groups. Pearson’s correlation showed significant connections between the cardiovascular risk factors and the results of the cognitive evaluation. Conclusions: Our results constitute additional evidence that cardiovascular risk factors are involved in cognitive regression. This finding could have an important impact on the management of dementia

The association between cholesterol levels and brachial/aortic augmentation index versus cognitive status in patients with cardiovascular risk factors

Cardiovascular pathology appears to have a major impact in cognitive decline, and early identification and correction of cardiovascular morbidity could have a major protective impact on cognitive functioning. However, it is not clear how the risk factors for vascular disease can also be risk factors for a general cognitive decline. Regarding cholesterol, its implications in cognitive decline are not very well understood, considering that a high level of cholesterol has been associated with both an increased and decreased risk of dementia. In the present context, we decided to study correlations between cholesterol concentration and the various subdomains of some main psychometric tests, such as MMSE (Mini-Mental State Examination) and MoCA (The Montreal Cognitive Assessment), as well as some measurements for systemic arterial stiffness (brachial and aortic augmentation index) and how they correlate with the aforementioned psychometric parameters. Our results provide additional evidence for a correlation between cholesterol levels and cognitive subdomains (with special focus on orientation, attention, recent memory and long-term memory). Additionally, a significant correlation was found between the brachial and aortic augmentation index and the results of both MMSE and MOCA tests

THE EFFECTS OF SHORT-TERM NICOTINE ADMINISTRATION ON BEHAVIORAL AND OXIDATIVE STRESS DEFICIENCIES INDUCED IN A RAT MODEL OF PARKINSON’S DISEASE

Background: We previously demonstrated that a 6-hydroxydopamine (6-OHDA) induced lesion of substantia nigra (SN), which is a very well known animal model of Parkinson’s disease, resulted in memory deficits and increased brain oxidative stress. Also, recent reports had suggested that nicotine from smoke may contribute, at least in some parts, to the apparent neuroprotective effect of tobacco use in Parkinson’s disease. Subjects and methods: In this way, in the present study we were interested to examine the effects of low-dose nicotine administration (5 days, 0.3 mg/kg/day) in a rat model of Parkinson’s disease, on behavioral parameters from Y-maze or shuttle-box task and also on the oxidative stress markers from the temporal lobe, which is one of the most vulnerable cortical area to oxidative stress effects. Results: The administration of nicotine resulted in significant improvements of short-term memory, as seen in the Y-maze task, as well an increase of conditioned avoidance responses and decreased number of escape failures in the shuttle-box task. Additionally, an increase in the specific activity of glutathione peroxidase and a decrease of the lipid peroxidation processes is reported. Moreover, we found a significant correlation between the behavioral results from the Y-maze and shuttle-box tasks and the levels of oxidative stress markers. Conclusions: Taken together our data suggest that short-term administration of low-dose nicotine facilitates memory processes and improves the oxidative stress status of the brain, after a 6-OHDA induced lesion of the SN

Establishing echocardiographic and arterial stiffness markers as predictors of cognitive decline

Different factors seem to contribute to cognitive impairment in the elderly population. It is unclear which cardiovascular risk factors are the most significant contributors to cognitive decline. Although there is some recent neuropathological evidence that vascular lesions and atherosclerotic occlusion of the cerebral arteries may unmask or strengthen the clinical expression of cognitive decline and dementia, there is still little knowledge about the relevance of echocardiographic and arterial stiffness markers as predictors for cognitive decline. In the present study we decided to investigate whether and how the severity of cognitive impairment could be related to cerebral hemodynamic impairment, as well as the possible contribution of the alterations in cerebral hemodynamics (as expressed through some echocardiographic and arterial stiffness markers) to the progression of cognitive decline in a group of patients with cognitive impairments, as compared to a control group with no cognitive deficits. The main finding of our study indicated significant differences in terms of echocardiographic and arterial stiffness markers between the two groups, one composed of patients with cognitive impairment and one with normal-cognitive patients, which suggests an association between these parameters and poor cognitive function. While these functional changes of the cerebral vessel functions could have an important role in the pathogenesis of dementia, the identification of simple and accurate measures that are acceptable to patients and can serve as indicators of current cognitive impairment or the risk of cognitive decline could be very helpful in developing long-term preventive and therapeutic treatments for these patients

OXIDATIVE STRESS IN SCHIZOPHRENIA - FOCUSING ON THE MAIN MARKERS

Oxidative stress is the condition arising from imbalance between toxic reactive oxygen species and antioxidant systems. It is believed that increased oxidative stress may be relevant to the pathophysiology of schizophrenia. In this way, the main markers of the lipid peroxidation processes include 4-hydroxynonenal and malondialdehyde. On the other side, the potential toxicity of free radicals is counteracted by a number of cytoprotective antioxidant enzymes that limit the damage, such as superoxide dismutase and glutathione peroxidase. However, the reports regarding the status of oxidative stress markers schizophrenia are very inconsistent, with various authors stating both increased and decreased activities of the main antioxidant enzymes, while others did not observe any significant modifications, as compared to control groups. Similar aspects were also reported in the case of the lipid peroxidation markers, although in here the contradictions are much more reduced than in the case of the antioxidant defences. It is generally believed that the equivocal results mentioned above may be due to different tissues studies, different species or the administrated treatment and the duration of the disease/treatment. In this context, in the present paper we were interested to review some studies regarding the oxidative stress status in patients and animal models of schizophrenia, by referring mainly to antioxidant enzymes and lipid peroxidation markers

HIPPOCAMPAL NEURONAL LOSS IN THE CA1 AND CA3 AREAS OF ALZHEIMER’S DISEASE PATIENTS

Background: It is believed that in Alzheimer’s disease (AD) some areas of the brain are particularly vulnerable to specific degenerative processes and that they could exhibit neuronal dysfunction in the earliest stage of the disease. The implications of the hippocampus in memory processes are very well known and it is likely that the hippocampus would be among the first areas of the brain affected by the pathogenic mechanisms occurring in AD. However, the distinction between the neurodegenerative changes that accompany normal ageing and those that characterize AD is not clear. Also, the distribution of the hippocampal cell loss in both normal aging and AD is not very well understood. Subjects and methods: In this context, we focused on the quantification of the neuronal density in the four specific areas of the hippocampus (CA1-CA4) of AD brains, as compared to an age-matched control group, by using the Nissl staining technique. Results: We found a significant reduction of neuronal density especially in the CA1 and CA3 hippocampal areas. The most prominent decrease was found at the CA1 area level, as compared to all other 3 areas which were analyzed. Conclusions: In the present study we managed to demonstrate and confirm a significant neuronal loss of hippocampus in AD, as compared to an age-matched control group. Moreover, it seems that this decrease of hippocampal neuronal density is more prominent especially at the CA1 and also in the CA3 hippocampal areas. This could have important implications in the design of therapeutic and investigative strategies of AD. However, larger samples are necessary in order to provide the basis for firmer conclusions in this area of research

Comparison between the effects of typical and atypical antipsychotics on oxidative stress status in schizophrenic patients

We determined the specific activities of some enzymatic antioxidant defenses like superoxide dismutase (SOD) and glutathione peroxidase (GPX), as well as a lipid peroxidation marker (MDA-malondialdehyde) from the serum of patients with schizophrenia treated with typical and atypical antipsychotics, in comparison with a normal age- matched control group. We observed an increased oxidative stress in schizophrenic patients treated with typical antipsychotics, compared to controls. Moreover, we demonstrated an antioxidant effect of atypical antipsychotics, since these patients showed an increased activity of SOD, compared to control subjects and a slightly decrease of MD

THE OXIDATIVE STRESS HYPOTHESIS IN ALZHEIMER’S DISEASE

Oxidative stress may be involved in many somatic and psychiatric pathological states including dementia. The hypothesis of oxidative stress involvement in dementia is supported by much scientific data through biochemical, genetic and molecular studies. Thus, there are many reports of an increased level of the markers for oxidative damage, alterations in the specific activity of the antioxidant system, mutations in specific genes, mitochondrial disturbances and also several connections between oxidative stress and amyloid plaques. Despite these evidence and clinical approaches in using antioxidant therapy in dementia treatment, studies have failed to prove a clear benefit for antioxidant treatment in dementia. Hence, there is a need for further research regarding antioxidant therapy in very early stages of dementia