In AD, tau protein is abnormally hyperphosphorylated. Significant changes of hyperphosphorylated tau levels in CSF are found in AD patients. It has been shown in vitro that memantine can reverse abnormal hyperphosphorylation of tau in hippocampal neurons of rats. A statistically significant reduction of CSF phosphorylated tau at a preliminary 1-year follow-up was observed, from median 126 (interquartile range 107-153) to 108 (88-133) ng/l (p = 0.018). No statistically significant differences of total tau or Aβ42 were found (Gunnarsson MD, 2007).

FDG-PET has the unique ability to estimate the local cerebral metabolic rate of glucose consumption, thus providing information on the distribution of neuronal death and synapse dysfunction in AD in vivo (Herholz K. 2003). Synaptic dysfunction and loss induce a reduction in neuronal energy demand that results in decreased glucose metabolism. Hypometabolism in AD is thought to reflect loss of synaptic activity and density (Herholz K. 2003; Mielke R, et al. 1998).

Another biological markers such as inflammatory factor and APOEε4 also play a part in the onset of AD (Glodzik-Sobanska L, 2007).

1. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on biological markers of subjects with Alzheimer's disease.
2. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on 18[F]-FDG-PET of brain in subjects with Alzheimer's disease.
3. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on cognitive function in subjects with Alzheimer's disease.
4. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on measures of behavior and activities of daily living of subjects with Alzheimer's disease.
5. To investigate the effects of daily dosing of memantine for 24 weeks versus placebo on short term memory.

Inclusion Criteria:

1. Written informed consent
2. Clinical diagnosis of Alzheimer's disease which meet the DSM-IV criteria.
3. Subject has moderate to severe Alzheimer's disease as defined by a MMSE score 4 to 20 inclusive at screening.
4. Hachinski Ischemia Score < 4 at screening.
5. Age ≥50 and ≤90 years.
6. Availability of a responsible and steady caregiver to ensure treatment compliance and provide information for assessments.

Exclusion Criteria:

1. Severe renal impairment.
2. History of seizures
3. Systolic blood pressure >160 or < 90 mmHg or diastolic blood pressure > 95 or < 60 mmHg at the time of screening.
4. Diagnosis of any concomitant life threatening illness.