Treatment of Psychosis and Agitation in Alzheimer's Disease

1. Male and female adults.

2. Diagnosis of possible or probable AD by standard NIA criteria (McKahnn et al, 1984; McKhann et all, 2011)

3. Folstein MMSE 5-26 out of 30

4. Neuropsychiatric Inventory (NPI) agitation/aggression subscale score > 4. On each subscale (frequency X severity), a score higher than 4 represents moderate to severe symptoms.

5. Female patients need to be post-menopausal

6. Availability of informant; patients without an informant will not be recruited. Patients who lack capacity must have a surrogate

1. Medical contraindication to lithium treatment or prior history of intolerability to lithium treatment.

Contraindications to lithium in this study include: resting tremor causing functional impairment, history of falls in the last month, untreated thyroid disease or any abnormal thyroid function test (T3, T4, or TSH), creatinine level greater than 1.5 mg/100ml or a glomerular filtration rate less than 44ml/min/ 1.73m2; blood pressure > 150/90 mm Hg; heart rate < 50 bpm; unstable cardiac disease based on history, physical examination, and ECG.

2. Medications, in combination with lithium, known to have adverse renal effects, including therapeutic or higher doses of diuretics, i.e. hydrochlorothiazide greater than 25mg daily or furosemide greater than 10mg daily. Whenever feasible, patients receiving concomitant antidepressants or antipsychotics will be washed off these medications for at least 24 hours before starting lithium. Patients who do not wish to discontinue antipsychotics or antidepressants, typically because of family member/caregiver objection, will be allowed to enter the trial provided there is no contraindication to concomitant lithium use with that specific psychotropic medication. During the trial, patients will be permitted to receive lorazepam as needed up to 1 mg/day for anxiety/insomnia, and non-benzodiazepine hypnotics, e.g., zolpidem.

3. Current clinical diagnosis of schizophrenia, schizoaffective disorder, other psychosis, or bipolar 1 disorder (DSM-IV TR criteria).

4. Current or recent (past 6 months) alcohol or substance dependence (DSM-IV TR criteria).

5. Current major depression or suicidality as assessed by the study psychiatrist.

6. Suicidal behavior or dangerous behavior with serious safety risk or risk of physical harm to self or others.

7. Parkinson's disease, Lewy body disease, multiple sclerosis, CNS infection, Huntington's disease, amyotrophic lateral sclerosis, other major neurological disorder.

8. Clinical stroke with residual neurological deficits. MRI findings of cerebrovascular disease (small infarcts, lacunes, periventricular disease) in the absence of clinical stroke with residual neurological deficits will not lead to exclusion.

9. Acute, severe, unstable medical illness. For cancer, patients with active illness or metastases will be excluded, but past history of successfully treated cancer will not lead to exclusion.

10. QTc interval > 460 ms at the time of baseline EKG is an exclusion criterion for treatment.

11. Hypernatremia as determined by serum sodium level > 150 meq/L.