Study design
In the proposed study, the patients will be divided into those receiving cholinesterase inhibitors (rivastigmine, galantamine and donepezil) and those receiving NMDA receptor antagonist therapy (memantine), based on the treatment they follow for AD. . A medical history of patients and controls, neuropsychological assessments using the respective questionnaires used in AD (which will be repeated at the end of the study-3 months) and a stool sample will be taken. Finally, a blood sample will be taken at the beginning of treatment to study P-gp ABCB1 gene polymorphisms and RLs and LPSs levels, and one at the end of the study to examinate drug levels RLs and LPSs levels in blood.
Duration:
Based on the required number of samples (patients and controls) the collection of these will last 6 months. Laboratory tests will take place in the next 12 months. Therefore, the main part of the study (sampling, laboratory analyzes) is expected to be completed in 18 months, while the stage of processing, analysis and verification of results is expected to last 6 months. The total duration of the study is expected to be 24 months.
Number of Subjects
135 subjects.
* 45 patients receiving treatment with cholinesterase inhibitors (rivastigmine, galantamine and donepezil).
* 45 patients receiving NMDA receptor antagonist (memantine).
* 45 healthy controls.
Patient Eligibility Screening Form (ESF):
An eligibility form documenting the patient's fulfillment of the entry criteria will be completed by the assessor. The following information will be included in the ESF:
* Patient identification: Initials (First initial of first name and first initial of surname), date of birth and Patient Identification Number.
* Written informed consent will be obtained from the subject. The informed consent form must be co-signed by the physician. The nature of the study and the potential risks associated with the trial will be explained to all subject candidates and their responsible informants.
* Signature and date: the ESF may be completed by an assessor but it is required that the principal investigator/study clinician sign and date the ESF to verify eligibility of the patient for inclusion.
Measured parameters:
For each patient who will participate in the study there should be a record of personal history that will include:
* Age
* Place of residence
* Eating habits (Mediterranean diet will be recommended)
* Smoking
* Medication followed in the last year
* Duration of the disease
* Other pathological conditions
Questionnaires
The neuropsychological assessment will include the following questionnaires, which are validated in Greek elderly population:
* Mini Mental Status Examination (MMSE)
* Montreal Cognitive Assessment (MoCA)
* Geriatrics Depression Scale (GDS)
* Functional or Cognitive Assessment scale (FUCAS)
Measurement methods
* The finding of P-gp ABCB1 gene polymorphisms will be performed with isolation of DNA with appropriate kits from the blood sample and will follow PCR technique with suitable primers and DNA electrophoresis or techniques real time PCR (taqman assay).
* Levels of RLs and LPs will be measured by the method ELISA and the use of corresponding antibodies.
* Drug levels in the blood will be measured by fluid high performance chromatography coupled to mass spectrometry (HPLC / MS).
