Assessment of apoptosis with celebrospinal fluid proteins and event related potentials in patients with mild cognitive impairment

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PhD thesis (EN)

2008 (EN)
Κλινική μελέτη της απόπτωσης με βάση πρωτεϊνες του εγκεφαλονωτιαίου υγρού και γνωσιακά προκλητά δυναμικά σε ασθενείς με ήπια νοητική έκπτωση
Assessment of apoptosis with celebrospinal fluid proteins and event related potentials in patients with mild cognitive impairment

Παπαλιάγκας, Βασίλειος Θ.

Patients with Patients with mild cognitive impairment (MCI) have memory problemsbigger than those expected due to aging, but do not experience any impairmentin any other cognitive functions such as thought, cognition and attentionor difficulties in daily life activities. Apoptosis is a normal procedure, essentialfor the development of multicellular organisms, and is believed to playa role in MCI pathogenesis.The aim of this study was the examination of the cognitive function ofMCI patients, the assessment of the apoptotic process, using measurementsof cerebrospinal fluid proteins levels, and the finding of potential correlationsbetween possible mechanisms involved in MCI and Alzheimer’s disease(AD).The study group consisted of a total of one hundred and twenty one (121)subjects of which ninety one (91) patients with MCI and thirty (30) healthycontrols. The mean±SD age of the patient group was 67.1±6.9 years (range46-83 years) and of the control subjects 68.7±9.9 years (range 49-90 years).The patient group consisted of 35 males and 56 females and the control groupof 15 males and 15 females. The two groups were matched for age (t-test,t=-0.96, p=0.34) and gender (―2=1.24, p=0.27).All subjects underwent:a) An examination with auditory event-related potentials (AERPs). The examwas performed in the Clinical Neurophysiology Department of the 3rdNeurological Clinic of the Aristotle University of Thessaloniki in the hospital“G.Papanikolaou”. From the 91 patients, who underwent an examwith AERPs, 43 were re-examined after an average period time of 12months (range 7-17 months) and 11 after an average time of 22 months(18-26 months) from baseline. 22 patients underwent a third examinationafter an average time of 23 (±3) months from baseline.b) The MMSE neuropsychometric test.151A clinical evaluation of the current disease situation was performed inMCI patients.Furthermore a lumbar puncture was performed in 54 patients and thelevels of the CSF proteins: beta amyloid1-42, tau, Bcl-2, Fas, Fas-L and cytochromec were determined. In 20 of these patients a second sample of CSFwas taken after an average period of 11.5 months. During the study period,five patients developed AD.A statistical analysis was performed in the results of all the parametersin control subjects and MCI patients.The results in the control subjects reveal a significant increase with ageof the latencies of the AERP waves N200, P300 and SW. Furthermore the latenciesof all waves correlate significantly with each other. Therefore it seemsthat each one is dependent upon the other. There is a highly significant associationbetween P300-N200 latency difference and P300, whereas similarcorrelation exists between the difference between SW and P300 latencies andthe difference between the latencies of SW and N200.The difference between SW and P300 latencies is highly correlated withSW wave latency and associated with P300 latency.From the statistical analysis of the results in the MCI patients, similarcorrelations as those of the control group were observed, except for the correlationsbetween latency differences SW-N200 and SW-P300 and SW-P300with latencies of P300 and SW, which do not exist in MCI patients.Moreover, no significant correlation was observed in MCI patients betweentheir performance in MMSE and the characteristics of the three AERPwaves.A significant increase was observed in N200 latency in the baseline examinationof the MCI patients that later developed AD. The use of a cut-offvalue of 300 ms resulted in a high sensitivity and specificity in the discriminationbetween MCI and AD patients. Therefore, there are indications thatN200 latency may serve as an accurate neurophysiological diagnostic markerfor the early diagnosis of AD. Moreover a significant correlation was observedbetween beta-amyloid levels and N200 latency both in the baseline andfollow up exam. The combination of these parameters (cut-off values >287ms for N200 latency and <500 pg/ml for beta-amyloid) has the maximum diagnosticaccuracy (100% sensitivity, 100% specificity) for the progression ofMCI patients to AD.A great increase in the levels of CSF tau protein (4-fold) was observed,152153in the small number of MCI patients that developed AD. A similar increasewas also noticed in the levels of Fas-L and cytochrome c in the same patients,a fact that supports the theory that apoptosis is involved in AD but not inMCI. On the other hand, in the MCI patients that did not develop AD, onlythe tau protein levels were increased.We believe that, these results, indicate that MCI and AD are two distinctand in many ways not relevant clinical entities. It may be that MCI serves asan aggravating factor for the development of AD but it is not a causal factorfor AD. Furthermore, in our view, the correlations that exist between CSFcytochrome c levels and N200 amplitude, as well as between CSF beta-amyloidlevels and N200 latency (which implies that N200 amplitudes are influencedby whatever processes accompany changes in beta-amyloid duringMCI), indicates that MCI probably attacks those cells of the human cortexthat are involved in lateral inhibition.
Σκοπός της διατριβής ήταν η εξέταση της νοητικής λειτουργίας ασθενών με ΗΝΔ, η αξιολόγηση της αποπτωτικής διαδικασίας, όπως αυτή προσδιορίζεται με την μέτρηση των επιπέδων πρωτεϊνών του εγκεφαλονωτιαίου υγρού και η εύρεση πιθανών συσχετίσεων με τους μηχανισμούς που εμπλέκονται στην ΗΝΔ και την ΝΑ, με τη χρήση και των αποτελεσμάτων από εξετάσεις με ΑΓΠΔ.

PhD Thesis / Διδακτορική Διατριβή

Πρωτεϊνες ΕΝΥ
Ηπια Νοητική Διαταραχή
Γνωσιακά προκλητά δυναμικά
Alzheimer's disease (AD)
Cognition disorders
Mild Cognitive impairment (MCI)
Νόσος Αλτσχάϊμερ (ΝΑ)
CSF proteins
Γνωστικές διαταραχές
P300 wave
Event related potentials

Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (EL)
Aristotle University of Thessaloniki (EN)



Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης, Σχολή Γεωπονίας, Δασολογίας και Φυσικού Περιβάλλοντος, Τμήμα Γεωπονίας

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