Please select the eligibility criteria that correspond to the clinical trial below.
Title: Memantine Versus Donepezil in Mild to Moderate Alzheimer's Disease. A Randomized Trial With Magnetic Resonance Spectroscopy.
Brief Summary: It is well known that in the brain of the patients with Alzheimer's disease there is a glutamatergic hyperstimulation leading to neuronal death. Memantine is a low affinity antagonist of NMDA glutamate receptors. The use of this drug in the early phases of the disease could provide neuroprotective effects and delay of progression. The effects of memantine should be compared to those of donepezil, which is the most prescribed anticholinesterase drug.


Options:
A: Inclusion Criteria:

1. Willingness to participate, as indicated by written informed consent of the patient. The competence of the participating patient has to be assessed by a physician who is not involved in this trial.
2. Male or postmenopausal female outpatients.
3. Age of \> 50 years at time of randomization.
4. Diagnosis of probable Alzheimer's Disease (according to NINCDS-ADRDA criteria).
5. Clinical and psychometric rating cut-off score (valid at randomisation): MMSE range of 15 to 26 points.
6. MRI brain scan not older than 12 months (before randomization) compatible with the diagnosis of Alzheimer's Disease. (The MRI brain scan must be repeated if older than 12 months or if clinically indicated).
7. Patient being ambulatory having adequate vision and hearing abilities to allow neuropsychological testing.
8. Patient with a knowledgeable, cooperative, reliable caregiver/informant who is willing to follow the study procedure as indicated by written informed consent.

Exclusion Criteria:

1. Dementia of any other type than AD:

   1. vascular dementia

      * HIS Score (modified acc. to Rosen) \> 5 or
      * evidence for VD acc. to NINCDS-AIREN criteria.
   2. depressive pseudodementia defined acc. to DSM-IV criteria for major depression.
   3. other non-AD dementia.
2. Significant neurological disease other than AD, such as cerebral tumor, Huntington's disease, Parkinson's disease, normal pressure hydrocephalus, subdural hematoma, mental retardation, history of brain surgery or serious head trauma with residual deficits.
3. Diagnosis of psychosis (requiring hospitalization or antipsychotic therapy for more than two weeks) within the past 10 years not associated with AD or a diagnosis of alcoholism or drug dependence within the past 10 years.
4. History of epileptic seizures or patient receiving antiepileptic drugs.
5. Abnormal laboratory test results considered clinically relevant for dementia: e.g., electrolyte changes, folate deficiency, vitamin B12 deficiency, pathological thyroid function (T3 and TSH levels), positive syphilis serology.
6. Patient who, in the opinion of the investigator, is suffering from an acute or poorly controlled illness, such as:

   1. Presently uncontrolled hypertension (\> 180 mmHg systolic or \> 100 mmHg diastolic).
   2. Myocardial infarction within the last six months.
   3. Patient with uncompensated congestive heart failure (NYHA Class III or IV)
   4. Severe renal, hepatic or gastrointestinal disease, which could alter absorption, metabolism or excretion of the trial drug.
   5. Serum creatinine \> 130 μmol/l or 1.5 mg/dl, transaminases (ALAT, ASAT) or GGT \> twice the upper limit of normal range.
   6. Uncontrolled diabetes on entry into the double-blind phase of the research project (fasting blood glucose \> 10.0 mmol/l or 180 mg/dl in repeated tests) or patient requiring insulin treatment.
7. Patient taking any inadmissible medication, such as:

   * Any investigational drug.
   * Anticonvulsants (incl. barbiturates).
   * Anti-Parkinson agents.
   * Dopaminergic agents.
   * Amantadine.
   * Antimuscarinic agents (i. e., anticholinergics).
   * Selegiline, MAOI.
8. Any condition that precludes cooperation with the tests or other investigations during the study (e.g., seeing or hearing loss, relevant confusion or agitation, musculoskeletal disorders, contraindication for magnetic resonance imaging, i.e., presence of pacemaker, metallic implants in high risk areas, presence of metallic material in high risk areas, history of claustrophobia. Hip implants are not contraindicated).
9. Patient has participated in an investigational clinical trial during the last 2 months.
B: Inclusion Criteria:

* Patients with MS (McDonald 2002), both sex, age between 18 to 60 years old, all MS subtypes (RR, SP, PP, PR), stable.
* Patients with severe cognitive impairment defined as performing 1.5 SD below control group (matched by age and education) in 2 o more subtests based in our previous study (Sepulcre 2006):

Exclusion Criteria:

* Psychiatric diseases (Cummings) depression (Hamilton \>8), drug or alcohol abuse, benzodiazepine therapy or other medical diseases.
C: Inclusion Criteria:

1. A diagnosis of multiple sclerosis as defined by the McDonald criteria. Patients with relapsing-remitting, secondary progressive, and primary progressive forms of MS are eligible.
2. Age between 18 and 65 years.
3. Demonstrated cognitive dysfunction at screening defined as a score worse than 1.0 standard deviations below the mean on the PASAT or the CVLT-II.

Exclusion Criteria:

1. A history of major depression, psychosis, or a score \> 19 on the Beck's Depression Inventory.
2. Corrected binocular visual acuity worse than 20/50; any impairment of binocular color vision.
3. Patients that do not speak English as a primary language (fluency may impact performance).
4. A clinically significant MS exacerbation within 30 days of the screening
5. Pregnancy
6. Renal insufficiency.
7. History of seizures.
8. Patients using acetazolamide (Diamox, Ak-sol, Storzolamide), dichlorphenamide (Daranide), methazolamide (Neptazane) or topiramate (Topamax), dextromethorphan (Robitussin DM and other cold remedies), or amantadine (Symmetrel).
9. Use of medical marijuana in the prior six months.
10. History of alcohol abuse or illicit drug use in the prior six months.
D: Inclusion Criteria:

* Clinical criteria of probable Alzheimer's disease in the stages mild-to-moderate with a Mini-Mental score higher than 15 points.

Exclusion Criteria:

* Previous treatment with anticholinesterase drugs or memantine.
* Advanced stages of the disease
* Lack of a reliable caregiver.
* Dementias other than Alzheimer's disease

Answer: D