LIWA for Treatment of Alzheimer Patients

Alzheimer's disease (AD) is the leading cause of dementia and cognitive deteriorating in the
advanced age. This main target of this study is to determine the safety and efficacy of
transcranial magnetic stimulation (TMS) using novel coil design (H2) for stimulation of deep
brain structures concomitantly with regular treatment in Alzheimer's disease (AD) patients.
TMS acts by generating magnetic fields in the brain which simulate neuro-chemical changes
and stimulate neuronal activity translating into increased secretion of growth factors such
as brain derived neurotropic factor (BDNF). Hence it is postulated that TMS will have a
positive effect on the cognitive and behavioral symptoms of patients with AD and may
ameliorated the progression of the disease. The treatment is non-invasive, with no
significant side effects, and no need of hospitalization or anesthesia. The trial is phase
II double blind study including 100 AD patients ages between 50 to 80 with mild or moderate
AD (Mini Mental State Examination [MMSE] 16 to 26) divided into 3 groups. All participants
will receive standard medical therapy for AD. In addition, patients recruited for the study
will receive 16 sessions of TMS with the H2 coil over 8 weeks. The first group will receive
excitatory stimulation of 10 Hz over the prefrontal and parietal cortex, the second group
will receive inhibitory stimulation of 1 Hz over similar brain areas and control patients
will receive the same amount of Sham sessions. Patient will receive 3 treatments per week in
the first 3 weeks and then 1 treatment per week for additional 4 weeks. Patients will be
evaluated before the treatments, after 8 weeks of treatment and after another 8 weeks
without treatment. The evaluations will include cognitive function according to ADAS-COG and
MMSE, Activity of daily living (ADL) functions according to ADSC-ADL, behavioral function
according to the Neuropsychiatric Inventory (NPI), depression according to the Cornell Scale
for Depression in Dementia (CSDD), care giver satisfaction according to the RUD LITE scale
and computerized cognitive evaluation according to the NEXING battery. We expect that the
cognitive, behavioral and ADL functions will improve better in the study group as compared
to the Sham treated group. From previous trial of TMS in neurological patients, although not
in AD, we anticipate that adverse events rate will be similar between groups proving the
safety of deep TMS treatment in patients with AD. In case our hypothesis will be proven,
deep TMS treatment will be added as an important modality to the conventional therapy of AD
patients.

All patients will be received 500 mcg/d of lithium as supplement nutritional in form spring
mineral water

Inclusion Criteria:

1. Men and women aged 50-85.

2. Diagnosed with Alzheimer's disease for at least half a year (by the DSM-IV criteria).

3. Scored 16-26 on the MMSE.

4. Received drug therapy for their disease, with each treatment having been administered
at an acceptable dosage for at least 5 weeks.

5. Existence of a routine therapist for changes or adverse effects reports.

6. Existence of Alzheimer diagnosis by CT or MRI tests.

7. Answered in the negative to all questions in the pre-TMS treatment safety
questionnaire.

8. Gave their oral and written consent to participate in the trial.

Exclusion Criteria:

1. An additional neurological disorder.

2. Severe psychiatric disorder.

3. Uncontrolled hypertension, beyond 170/110.

4. History of epilepsy, seizure, or heat convulsion or History of epilepsy or seizure in
first degree relatives.

5. History of head injury or stroke.

6. History of metal implants in the head (except dental fillings)or History of surgery
entailing metallic implants or known history of any metallic particles in the eye,
implanted cardiac pacemaker, cochlear implants, use of neuro stimulators, or any
medical pumps.

7. History of migraines in the last six months.

8. History of drug or alcohol abuse.

9. Inadequate communication with examiner.

10. Participation in another clinical study, either concurrent with this trial or in the
3 months preceding it.

11. Inability to sign a consent form.

12. Leukemia