Transcranial Magnetic Stimulation for Apathy in Mild Cognitive Impairment:Pilot Study

Mild cognitive impairment (MCI) is a precursor of dementia. Apathy, a profound loss of motivation, is a common behavioral problem in MCI. Presence of apathy may increase the chance of MCI patients converting to Alzheimer's Dementia. Repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive tool, has been recently approved for treatment of refractory depression. Since dysfunction in the frontal lobe of the brain is seen in patients with apathy, rTMS to the frontal lobe might be helpful in treating the same. Study hypotheses include that rTMS to the dorsolateral prefrontal cortex (DLPFC) will improve apathy and executive function better than sham treatment in those with MCI

Objective: Mild cognitive impairment (MCI) is a precursor of dementia. Apathy, a profound loss of motivation, is a common behavioral problem in MCI. Presence of apathy may increase the chance of MCI patients converting to Alzheimer's Dementia. Repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive tool, has been recently approved for treatment of refractory depression. Since dysfunction in the frontal lobe of the brain is seen in patients with apathy, rTMS to the frontal lobe might be helpful in treating the same.

Specific Aims:

* To determine the efficacy of rTMS to the dorsolateral prefrontal cortex (DLPFC) in treating apathy in MCI in comparison to sham treatment.
* To compare the efficacy of rTMS to the DLPFC on executive function in MCI in comparison to sham treatment.

Research Plan: Current study is a randomized sham controlled cross-over study of daily rTMS.

Methods: 20 subjects with MCI and apathy will be enrolled to randomize 8 to a total of 20 sessions of treatment (2 weeks sham, 2 weeks rTMS, with 4 weeks of washout period). Subjects will be randomly assigned to rTMS or sham treatment after consent. After 2 weeks of treatment there will be a 4 week period with no treatment. At the end of the 4-week wash out period, subjects will be crossed over to the next treatment arm (i.e. those who received rTMS in the beginning will receive sham treatment and vice versa). Subjects will be followed for four additional weeks after treatment. Apathy will be assessed using the Apathy Evaluation Scale. Memory, executive function, functional status and caregiver burden will be assessed.

Eligibility Criteria:
Inclusion Criteria:

1. Subjects age ≥ 55 years,
2. Subjects meeting Petersen's criteria for MCI,
3. Apathy Evaluation Scale-Clinician (AES-C) score of ≥ 30,
4. Mini Mentla Status Examination (MMSE) ≥ 23,
5. Subjects who clear the TMS adult safety scale (TASS)
6. On stable dose of antidepressants (if applicable) for at least two months

Exclusion Criteria:

1. Subjects taking medications known to increase the risk of seizures from the 2012 Beers criteria: Bupropion, chlorpromazine, clozapine, maprotiline, olanzapine, thioridazine, thiothixene, and tramadol.
2. Subjects taking medications known to increase seizure threshold not listed in the Beers criteria but in the opinion of PI increase seizure threshold: tricyclic antidepressants, theophylline, methylphenidate, and high-dose thyroid supplementation.
3. Subjects taking ototoxic medications: Aminoglycosides, Cisplatin.
4. Subjects in current episode of major depression
5. History of bipolar disorder
6. Subjects with history of seizure or first degree relative with seizure disorder
7. Subjects with implanted device: wearable or implantable cardioverter defibrillators, conductive, ferromagnetic, or other magnetic sensitive metals that are implanted or are non-removable within 30 cm of the treatment coil or those with cochlear implants
8. Subjects with diagnosis of current alcohol related problems
9. Subjects with history of stroke , aneurysm, or cranial neurosurgery
10. Any condition that in the opinion of the study physician is likely to compromise their ability to safely participate in the study