Enhancing Frontal Lobes Plasticity in Mild Cognitive Impairment (PAS-MCI)

This is an interventional treatment trial for Mild Cognitive Impairment focused on measuring Memory Impairment, Executive Function, Transcranial Magnetic Stimulation, Paired Associative Stimulation, Neuroplasticity, Electroencephalography, Working Memory, Cognition, Prefrontal Cortex Read More

MCI Group:

Inclusion Criteria:

1. Age 60 years or above.
2. Right-handed (to minimize heterogeneity with respect to cognitive reserve and plasticity) and as determined by the Edinburgh Handedness Questionnaire.

3. Diagnosis of MCI due to AD using the core clinical criteria by the National Institute on Aging and Alzheimer's Association for MCI participants (NIA-AA) and ascertained by a study investigator. The following checklist will be used to ascertain the MCI diagnosis:

   1. Cognitive concern reflecting a change in cognition reported by patient or informant or clinician (i.e., historical or observed evidence of decline over time).
   2. Not demented ascertained using the study investigator opinion.
   3. No vascular, traumatic, or medical causes of cognitive decline ascertained using the study investigator opinion.
   4. Evidence of longitudinal decline in cognition, when feasible, and ascertained using the study investigator opinion.
4. Objective evidence of single or multi domain MCI, where single domain MCI refers to deficits using NP battery on only one of the cognitive domains (Speed of Processing; Working Memory; Executive Functioning; Verbal Memory; Visual Memory; Language)and multi domain MCI refers to deficits in more than one of these domains. To determine impairment in one or more cognitive domain, , after the NP battery is administered and double scored, a consensus meeting will be held with the Research Analyst/Fellow, the study Principal Investigator and the study Neuropsychologist during which eligibility will be discussed. The meeting attendees will take into consideration the participant's education, parental education, pre-morbid IQ, physician's assessment and NP scores to determine if the participant has impairment in one or more cognitive domain.
5. Willingness to provide informed consent.
6. Ability to read and communicate in English (with corrected vision and hearing, if needed).

Exclusion Criteria:

1. Current use of an acetylcholine esterase inhibitor or memantine ascertained using a Medication List.
2. Major Depressive Disorder with active symptoms in the last 3 months ascertained using the Structured Clinical Interview for DSM 5 (SCID-5).
3. A lifetime diagnosis of bipolar disorder; intellectual disability; or a psychotic disorder ascertained using the SCID-5.
4. Substance use disorder active in the last 3 months ascertained using the SCID-5.
5. Any other DSM-5 diagnosis ascertained using the SCID-5 that may be associated with prefrontal cortical dysfunction as ascertained using a study investigator opinion.
6. Current anticonvulsant use due to its impact on TMS induced activity and ascertained using a Medication List. An exception will be made if they are taking gabapentin or pregabalin AND if the dose had been stable for at least 4 weeks prior to study entry AND if prescribed for chronic pain.
7. Current benzodiazepine use of more than what is equivalent to lorazepam 2 mg/day as ascertained using a Medication List. This is due to their known pro-GABAergic activity and the suppressive effect of GABAergic agents on cortical plasticity.
8. Any contraindication to MRI or contraindication to TMS (e.g., cardiac pacemaker, acoustic device, history of seizures) ascertained using the TMS Adult Safety Screen (TASS).

Healthy Controls

Inclusion Criteria:

1. Age 60 years or above.
2. Right-handed (to minimize heterogeneity with respect to cognitive reserve and plasticity) and as determined by the Edinburgh Handedness Inventory.
3. MoCA score > 26.
4. Ability to read and communicate in English (with corrected vision and hearing, if needed).
5. Willingness to provide informed consent.

Exclusion Criteria:

1. Diagnosis of MCI due to AD using the core clinical criteria by the National Institute on Aging and Alzheimer's Association for MCI participants and ascertained by a study investigator.
2. Any lifetime DSM-5 diagnosis ascertained using the SCID-5 (except for simple/specific phobias) or diagnosis that may be associated with prefrontal cortical dysfunction as ascertained using a study investigator opinion.
3. Any current use of a psychotropic medication for a CNS condition as ascertained using the Medication List.
4. Current anticonvulsant use due to its impact on TMS induced activity and ascertained using a Medication List. An exception will be made if they are taking gabapentin or pregabalin AND if the dose had been stable for at least 4 weeks prior to study entry AND if prescribed for chronic pain.
5. Current benzodiazepine use of more than what is equivalent to lorazepam 2 mg/day as ascertained using a Medication List. This is due to their known pro-GABAergic activity and the suppressive effect of GABAergic agents on cortical plasticity.
6. Any contraindication to MRI or contraindication to TMS (e.g., cardiac pacemaker, acoustic device, history of seizures) ascertained using the TMS Adult Safety Screen (TASS).