Effects of Memantine on Magnetic Resonance (MR) Spectroscopy in Subjects at Risk for Alzheimer's Disease
Status:
Completed
Trial end date:
2011-09-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 4
Details
Lead Sponsor:
New York University School of Medicine NYU Langone Health