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Vesna Jelic

Publications and source records attributed to Vesna Jelic.

8 recordsLinked to original sources

Effects of statins on cognitive function in patients with Alzheimer's disease in galantamine clinical trials.

BACKGROUND AND OBJECTIVE: A number of reports have been published on the possible involvement of changes in brain cholesterol metabolism in the origin of Alzheimer's disease (AD) and the potential for influencing these changes by administration of HMG-CoA reductase inhibitors ('statins'). The aim of this study was to evaluate a potential association between use of statins and maintenance of cognitive function in patients with AD in galantamine clinical trials. METHOD: A post hoc analysis was conducted on data pooled from three double-blind, placebo-controlled, clinical trials of galantamine in patients with AD. Patients were divided into four treatment groups: statin plus galantamine (n = 42), statin alone (n = 50), galantamine alone (n = 614) or neither galantamine nor statin (n = 619). RESULTS: Galantamine was associated with a significant beneficial effect on cognitive status (p < 0.001). The association of use of statins with changes in cognitive status was not significant (p = 0.083). There was no significant interaction between the effects on cognition of statins and galantamine (p = 0.183) and no statistically significant changes in adverse effect rates were observed. CONCLUSION: These findings suggest the need for larger long-term trials to confirm or refute possible effects of statins on cognitive function and the potential interaction of statins with acetylcholinesterase inhibitors in the treatment of AD.

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Application and comparison of classification algorithms for recognition of Alzheimer's disease in electrical brain activity (EEG).

The early detection of subjects with probable Alzheimer's disease (AD) is crucial for effective appliance of treatment strategies. Here we explored the ability of a multitude of linear and non-linear classification algorithms to discriminate between the electroencephalograms (EEGs) of patients with varying degree of AD and their age-matched control subjects. Absolute and relative spectral power, distribution of spectral power, and measures of spatial synchronization were calculated from recordings of resting eyes-closed continuous EEGs of 45 healthy controls, 116 patients with mild AD and 81 patients with moderate AD, recruited in two different centers (Stockholm, New York). The applied classification algorithms were: principal component linear discriminant analysis (PC LDA), partial least squares LDA (PLS LDA), principal component logistic regression (PC LR), partial least squares logistic regression (PLS LR), bagging, random forest, support vector machines (SVM) and feed-forward neural network. Based on 10-fold cross-validation runs it could be demonstrated that even tough modern computer-intensive classification algorithms such as random forests, SVM and neural networks show a slight superiority, more classical classification algorithms performed nearly equally well. Using random forests classification a considerable sensitivity of up to 85% and a specificity of 78%, respectively for the test of even only mild AD patients has been reached, whereas for the comparison of moderate AD vs. controls, using SVM and neural networks, values of 89% and 88% for sensitivity and specificity were achieved. Such a remarkable performance proves the value of these classification algorithms for clinical diagnostics.

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Treating the full spectrum of dementia with memantine.

An increasing number of elderly people result in increased social and economical impact of dementia, particularly its most common form Alzheimer's disease (AD). Dementia itself consists of a wide spectrum of disease, ranging from the mild cognitive impairment that progresses through several clinical milestones to advanced dementia. Drugs available at the moment on the market are approved for the treatment of mild to moderate dementia and their symptomatic effect is based on cholinergic substitution. However, the largest amount of costs utilised for dementia is institutional care for severely affected patients. At this stage of the disease both vascular and degenerative mechanisms contribute to the clinical expression of the disease. Recent clinical trials with the antiglutamatergic drug memantine have shown that cognitive benefit could be observed in patients with vascular dementia and reduced care dependence in those with moderately severe to severe form of the disease. The later findings are results from the M-BEST study, which is briefly rewieved here with some of the epidemiological, socioeconomical and clinical implications of such therapy.

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A critical discussion of the role of neuroimaging in mild cognitive impairment.

OBJECTIVE: In this paper, the current neuroimaging literature is reviewed with regard to characteristic findings in mild cognitive impairment (MCI). Particular attention is drawn to the possible value of neuroimaging modalities in the prediction and early diagnosis of Alzheimer's disease (AD). METHODS: First, the potential contribution of neuroimaging to an early, preclinical diagnosis of degenerative disorders is discussed at the background of our knowledge about the pathogenesis of AD. Second, relevant neuroimaging studies focusing on MCI are explored and summarized. Neuroimaging studies were found through Medline search and by systematically checking through the bibliographies of relevant articles. RESULTS: Structural volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET)/single photon emission tomography (SPECT) are currently the most commonly used neuroimaging modalities in studies focusing on MCI. There were considerable variations in demographical and clinical characteristics across studies. However, significant hippocampal and entorhinal cortex volume reductions were consistently found in subjects with MCI as compared with cognitively unimpaired controls. While hippocampal and entorhinal cortex atrophy in subjects with MCI are also well-established risk factors for the development of AD, these measures cannot be regarded as being of high predictive value in an individual case. Evidence for other typical neuroimaging changes in MCI is still scarce. In PET and SPECT studies, reduced blood flow and/or glucose metabolism in temporoparietal association areas, posterior cingulate and hippocampus were associated with a higher risk of progressive cognitive decline in MCI. In quantitative electroencephalogram (QEEG), low beta, high theta, low alpha and slowed mean frequency were associated with development of dementia. CONCLUSIONS: Existing studies suggest that neuroimaging measures have the potential to become valuable tools in the early diagnosis of AD. To establish their value in routine use, larger studies, preferably with long prospective follow-up are needed.

Alzheimer Disease↗

Treatment of mild cognitive impairment: rationale, present and future strategies.

Mild cognitive impairment (MCI) is a condition with a high conversion rate to Alzheimer's disease (AD), which justifies early diagnostic and therapeutic interventions. At the moment, treatment strategies for AD could be extrapolated to interventional strategies in MCI. This article reviews currently available symptomatic treatments with acetylcholinesterase inhibitors, putative treatments such as antiglutamatergic drugs, nootropics, antioxidants, anti-inflammatory drugs and still controversial estrogen replacement therapy, and visionary treatments targeting neuropathological substrates of the disease, such as amyloid production and aggregation, phosphorylation of tau, formation of neurofibrillary tangles and apoptosis. Findings from epidemiological studies have expanded our knowledge on risk as well as possible neuroprotective factors and given means to develop preventive strategies with antihyperlipidaemic drugs such as statins. A wide range of suggested treatments and their possible combinations necessitate their efficacy assessment in well-designed randomized clinical trials where the crucial prerequisites are selection of the treatment population and definitions of outcome measures. Prevention and disease-modifying strategies are raising ethical questions because interventions are focused on non-diseased elderly at risk, which means that emphasis should be not only on efficacy but also on long-term safety.

Animals↗

Long-term treatment of Alzheimer disease: efficacy and safety of acetylcholinesterase inhibitors.

During the past 20 years, research on Alzheimer disease (AD) and other dementias has increased our understanding of these disorders and has opened doors to new methods of treatment. Acetylcholinesterase inhibitors (AChEIs) have been successful in reducing symptoms in patients with mild-to-moderate AD and led to the US Food and Drug Administration's approval of four AChEIs for the treatment of AD. Although these agents are approved for only mild-to-moderate AD, and the available data for most of them are from trials of only 6 months' duration, long-term studies suggest that the benefits of AChEI treatment can endure for up to 4 years. A common pattern of response to treatment is initial improvement in cognition, followed by maintenance of cognitive gains above baseline for up to 1 year. Generally there is a decline in cognition to below baseline levels after approximately 1 year of treatment, but the level of cognition remains above that predicted for those not receiving pharmacologic treatment. Furthermore, long-term studies suggest that early diagnosis and treatment with AChEIs yield better long-term outcomes. Patients who received continuous pharmacologic treatment from the outset generally had better long-term outcomes than those who received placebo in the double-blind phase of these trials.

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