Effects of Memantine on Magnetic Resonance (MR) Spectroscopy in Subjects at Risk for Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: memantine; Placebo
Intervention description: participants will be asked to take memantine (20mg/day) for 16 weeks; participants will be asked to take 2 tablets per day to match active drug
Intervention MeSH terms: Memantine
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 17.0
Sex: All
Minimum age: 55 Years
Maximum age: 90 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: subjective memory complaints; cognitively healthy; family history; AD

Summary:

      Recent data show that marked cell damage precedes the clinical manifestation of Alzheimer's
      disease (AD). Hence, targeting populations at risk with pharmacological interventions is a
      possible strategy to lessen the burden of the disease. Cognitively normal individuals with
      subjective memory complaints (SMC) manifest biological characteristics consistent with early
      AD and are at risk for future cognitive decline. Family history of AD also constitutes a
      risk. In a previous study the investigators showed that memantine slows down the accumulation
      of phosphorylated tau in normal SMC subjects. Using a multivoxel high field MR spectroscopy
      (MRS) technique, the investigators also demonstrated that memantine decreased hippocampal
      glutamate. Both these findings may be consistent with the drug's anti-excitotoxic activity.
      In this new project the investigators propose to treat a sample of 12 presymptomatic
      individuals at risk (SMC and family history of AD) with memantine. This will be a double
      blind, placebo controlled study with a control group (12 non-treated subjects). The
      investigators will determine whether the effects of memantine as assessed by cognitive
      performance and MRS are present after 4 months of treatment and persist 2 months after
      discontinuation. MRS will be used to evaluate the effect of memantine on levels of the
      neurotransmitter glutamate and neuronal viability marker N-acetylaspartate (NAA) in the
      hippocampus. The investigators will test the following hypotheses:

        1. In subjects with SMC, memantine has modifying effects on brain biochemistry as reflected
           in MRS reductions in glutamate (reduced excitotoxicity) and increases in NAA (neuronal
           integrity).

        2. The effects of the drug persist (as a marker of sustained neuroprotection) and can be
           measured 2 months after discontinuation of the treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  presence of subjective memory complaints without objective evidence of impaired
             cognition

          -  family history of Alzheimer's disease

        Exclusion Criteria:

          -  major depression

          -  Parkinson's disease

          -  stroke

          -  seizures

          -  uncontrolled diabetes or hypertension

          -  current benzodiazepine use

          -  substance abuse

          -  contraindication for MRI

          -  contraindications for memantine