Brain Changes by Rivastigmine According to Butyrylcholinesterase Alleles

Differences of Functional Changes in Brain by Rivastigmine According to Butyrylcholinesterase Alleles in Alzheimer's Disease Patients(Rivastigmine, Imaging, and BuChE in AD: RIBA)

Butyrylcholinesterase (BuChE) activity is increasing in Alzheimer Disease (AD) process (Lane et al., 2006). BuChE wild type has stronger butyrylcholine esterase activity than BuChE K variant allele and this strong activity can affect AD brain negatively by choline depletion. Rivastigmine has unique dual action - acetylcholine esterase inhibition and butyrylcholine esterase inhibition. Therefore, rivastigmine can lower serum butyrylcholine esterase activity and delay functional decrease of Fluorodeoxyglucose positron emission tomography (FDG PET) images in AD patients with BuChE wild type allele by strong BuChE inhibition.

It suggests that rivastigmine can affect brain function differently by BuChE genotype in AD. Therefore, we will try to find the different changes of serum butyrylcholine esterase activity by ELISA and functional and structural changes of brain between BuChE wild type and K-variant type by FDG PET and MRI pre and post images after 12 month use of rivastigmine.

1. Primary objective:

   1. the mean changes of Standardized Uptake Values (SUVmean) in PET imaging
   2. the mean changes of serum BuChE activity between BuChE wild type and K-variant type.

2. Secondary objectives:

   1. the mean changes of cortical thickness in brain MRI
   2. the cognitive changes in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)
   3. the cognitive changes in Mini-Mental State Exam (MMSE)
   4. the daily function changes by Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
   5. the behavioural changes by Caregiver-Administered Neuropsychiatric Inventory (NPI)
   6. the disease severity changes by Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) between BuChE wild type and K-variant type.

Inclusion Criteria:

• Clinical diagnosis of Alzheimer's Disease (NINCD-ADRDA and MMSE between 10 ~26)
• Who didn't take Cholinesterase Inhibitor on liver within 3 months

Exclusion Criteria:

• diagnosed with diseases other than AD that affect brain atrophy according to Brain MRI
• Diagnosed with diseases other than AD which affect cognitive functions (i.g. Schizophrenia, Major Depression, Mental Retardation, encephalopathy, etc.)
• Didn't suspect of drug or alcohol addictions within last decade
• Unable to participate the study due to poor sight and hearing
• Who aren't suitable to participate according to the researchers' judgement