Please select the eligibility criteria that correspond to the clinical trial below.
Title: Study of Memantine to Treat Gait Disorders And Attention Deficit In Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Monocentric Trial
Brief Summary: Along with cognitive and psychobehavioural disorders, gait disorders represent a major problem in the treatment of advanced Parkinson's disease (PD). PD can be considered to be a hyperglutamatergic disease because dopaminergic depletion induces hyperactivity of the subthalamic nucleus (STN) and the internal pallidum (GPi), with glutamatergic hyperactivity of the STN's efferent pathway, i.e., the subthalamopallidal, subthalamonigral and subthalamo-entopeduncular pathways (projecting to the pedunculopontine nucleus (PPN)). Excess glutamate in the PPN has also been observed in the 6-OHDA rat model of PD. Reduction of this glutamatergic hyperactivity within the PPN via the systemic or intra-peduncular administration of glutamate antagonists improves akinesia in drug-induced murine and primate models of PD, via the NMDA and AMPA receptors. High doses of memantine (10 mg/kg) improve locomotion in reserpine- and alpha-methyl-p-tyrosine-treated rats. In humans, the PPN may play a key role in gait, posture control, axial rigidity and attention. It is also involved in the gating of sensory information involved in the startle reflex, which can be studied via prepulse inhibition (PPI) of the blink reflex. At present, two uncompetitive NMDA receptor antagonists are approved for use in humans: amantadine and memantine. Reviews of the recent literature on these drugs have identified no published studies specifically on severe gait and attention disorders in PD. Memantine is a partial blocker of open NMDA channels. The value of memantine relates to the fact that it decreases excessive glutamatergic transmission by lowering the synaptic noise due to excessive activation of NMDA receptors. In this double-blind study, the investigators shall seek to demonstrate the presence or absence of an effect of memantine on gait and attention disorders. In order to study the interaction between glutamatergic hyperactivity and the dopaminergic system, the investigators shall study the phenomena both in the absence of L-dopa and following acute administration of the latter. Twenty eight volunteer, non-demented, late-stage PD patients displaying severe gait disorders will receive memantine (20 mg/day) or placebo for 3 months. The investigators expect to see a reduction in gait and attention disorders, together with an improvement in the blink reflex with PPI under memantine. This pilot study could subsequently be turned into a double-blind, placebo-controlled multicenter study.


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:

* Parkinson's disease of more than 5 years
* Subthalamic nucleus stimulation
* Gait disorders impeding moderately to severely the activities of daily living
* gait disorders including freezing of gait
* able to walk without physical assistance

Exclusion Criteria:

* Dementia (MMSE \< 27 et score de Mattis \< 130)
* Requiring dopatherapy modification
* Requiring subthalamic stimulation parameters adaptation
* Psychiatric disorders: hallucinations, unstable thymic disorders, psychosis)
* Cardiac disorders: dysrhythmia or unstable arterial hypertension
* Unstable or severe medical illness
* intolerance or contraindication to memantine
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:

1. Diagnoses of possible or probable Alzheimer's disease (NINCDS-ADRDA)
2. Presence of a caregiver (friend or relative) who can assume responsibility for medication compliance, can accompany the patient to all visits, and rate patient's condition
3. Written informed consent from both the patient (or surrogate) and caregiver
4. An MMSE score between 12 and 26 inclusive
5. Administration of a maintenance dosage of donepezil (5-10mg/d), rivastigmine (6-12mg/d) or rivastigmine (Exelon) patch (4.6 mg or 9.5 mg), galantamine or galantamine ER (16-24mg/d) for a minimum of 4 weeks prior to randomization
6. Agreement not to take vitamin E supplements and/or memantine outside of the study (daily multivitamin is permitted containing up to 100 IU alpha-tocopherol)

Exclusion Criteria:

1. A non-Alzheimer primary dementia (e.g., vascular dementia, Lewy body dementia, fronto-temporal dementia, vitamin B-12 deficiency, hypothyroidism)
2. Current major depression, delirium, alcohol or psychoactive substance abuse or dependency, schizophrenia, or delusional disorder as defined by DSM-IV
3. Presence of any uncontrolled systemic illness that would interfere with participation in the study or a life expectancy of less than one year
4. Pregnant or intention to become pregnant
5. Enrollment in another interventional clinical trial
6. Current prescription with more than one AChE inhibitor
7. Current prescription for warfarin
8. Use of vitamin E supplements in the past 2 weeks
9. Use of memantine in the past 4 weeks or known intolerance
10. Estimated creatinine clearance less than 5ml/min (Cockcroft-Gault formula)
11. Use of amantadine in the past 2 weeks

Answer: B