Multidisciplinary Study of Novel NMDA Modulation for Neurodegenerative Disorder

Multidisciplinary Study of Novel NMDA Modulation for Neurodegenerative Disorder

Alzheimer's disease (AD) and Parkinson's disease (PD) are currently the leading neurodegenerative disorders. Considering the fact that aged population is rapidly growing, it has become a critical issue to find more effective medications for these two disorders. The aim of this project is to examine the effectiveness and safety of DAAOI-P treatment for PD with dementia.

Alzheimer's disease (AD) and Parkinson's disease (PD) are currently the leading neurodegenerative disorders. Despite some therapeutic benefits from the medications targeting at cholinergic and dopaminergic pathways in AD and PD respectively, it remains far away from a satisfied treatment goal. DAAOI-P is a D-amino acid oxidase (DAAO) inhibitor and an agent specific to facilitate NMDA receptor subunit 1 (NR1). The investigators have demonstrated that NMDA-enhancement can help PD-D patients. The aim of this project is to examine the effectiveness and safety of DAAOI-P treatment for PD with dementia. In addition to evaluating clinical treatment response, multidisciplinary examinations, including electroencephalography, transcranial magnetic stimulation, magnetic resonance imaging (MRI), and psychophysical methods to analyze the changes in perceptual sensitivity to faces, emotion expressions, and biological motion recognition will be arranged to elucidate the underlying mechanism of NMDA modulation in neurodegenerative disorder.

Inclusion Criteria:

• PD-D will be diagnosed according to the criteria proposed by Movement Disorder Society task force statement. (Emre et al. 2007) . The following wordings are modified from the task force statement. I. Core features

  1. Diagnosis of PD according to Queen Square Brain Bank criteria

  2. A dementia syndrome with insidious onset and slow progression, developing within the context of established PD and diagnosed by history, clinical, and mental examination, defined as:

     • Impairment in more than one cognitive domain
     • Representing a decline from premorbid level
     • Deficits severe enough to impair daily life, independent of the impairment ascribable to motor or autonomic symptoms
     • MMSE score between 10-26.

II. Associated clinical features

1. Cognitive features: Impaired attention, executive functions, visuo-spatial functions or memory. Core functions of language are largely preserved.

2. Behavioral features:

   • Apathy
   • Changes in personality and mood
   • Hallucination• Delusions
   • Excessive daytime sleepiness

III. Features which do not exclude PD-D, but make the diagnosis uncertain

• Co-existence of any other abnormality which may by itself cause cognitive impairment, but judged not to be the cause of dementia.
• Time interval between the development of motor and cognitive symptoms is uncertain

IV. Features suggesting other conditions or diseases as cause of mental impairment, which, when present make it impossible to reliably diagnose PD-D

• Cognitive and behavioral symptoms appearing solely in the context of other conditions such as:

  1. Acute confusion due to systemic illnesses or drug intoxication.
  2. Major depression

• Features compatible with "Probable Vascular dementia" criteria according to NINDS-AIREN Criteria for the diagnosis of probable and possible PD-D [Probable PD-D] Both core features must be present. In associated clinical features, typical profile of cognitive deficits should be present in at least 2 of the 4 core cognitive domains. The presence of at least one behavioral symptom supports the diagnosis of probable PD-D. None of group III and IV features is present. [Possible PD-D] Both core features must be present. In associated clinical features, the cognitive impairment is atypical in one or more domains. The behavioral symptoms are not necessary to be present. One or more of the group III features may be present. No group IV feature is allowed to be present.

Exclusion Criteria:

1. Patients with uncontrollable malignancy, severe heart failure, uremia under hemodialysis, or decompensated liver cirrhosis.
2. Patients taking anticholinergics within 30 days of recruitment.