The overall goals of this project are to assess the feasibility and impact of designing and implementing an at-home intervention aimed at preventing long-term cognitive decline and improving cognition in individuals currently at-risk for developing AD.

By the time Alzheimer's Dementia (AD) and related disorders are diagnosed, the brain has sustained substantial insult that limits the efficacy of current treatments. Preventive interventions are urgently needed but the majority of prevention studies require large numbers of participants, long follow-up periods, and frequent study visits. It is not feasible for many geriatric patients to attend clinics for treatment on a daily basis due to mobility and transportation restrictions, associated costs, and lack of rural clinic locations. Interventions delivered remotely, or administered within an individual's home, allow for preventative treatments to be made accessible to a wider range of individuals. Thus, the overall goals of this project are to assess the feasibility and impact of designing and implementing an at-home intervention aimed at preventing long-term cognitive decline and improving cognition in individuals currently at-risk for developing AD. These high-risk individuals that will be targeted in this proposal are: (1) older adults with Mild Cognitive Impairment (MCI), (2) older adults with Major Depressive Disorder (MDD), and (3) older adults with MCI and MDD.

The proposed intervention combines cognitive remediation (CR) and non-invasive brain stimulation - transcranial Direct Current Stimulation (tDCS), to be delivered in the participants' home environment. Twenty couples (40 participants) will be recruited, with one member defined as the "patient" and the second member defined as the "caregiver" to the patient. These caregivers will facilitate the delivery of the study intervention (i.e., CR+tDCS). Participants with a diagnosis of MCI or MDD or both, who have a caregiver, will receive open-label, active CR+tDCS over a period of 8 weeks. Both CR and tDCS have been shown to induce neuroplasticity and improve cognition. The aim of this pilot study is to assess the feasibility of delivering these combined interventions at home.

MCI Group

Inclusion:

1. Age > 60 (on day of randomization)
2. DSM-IV criteria for Mild Neurocognitive Disorder ("MCI")
3. Willingness to provide informed consent
4. MADRS score of 10 or below
5. Availability of a study partner who has regular contact with the participant
6. Ability to read and communicate in English (with corrected vision and hearing, if needed)

Exclusion:

1. Met DSM-IV criteria for Major Depressive Episode in past 10 years
2. Lifetime DSM-IV diagnosis of schizophrenia, bipolar disorder, or OCD
3. DSM-IV diagnosis of alcohol or other substances use disorder within the past 12 months
4. High risk for suicide
5. Significant neurological condition (e.g., stroke, seizure disorder, MS)
6. Unstable medical illness, (e.g., uncontrolled diabetes mellitus or hypertension)
7. Having taken a cognitive enhancer (acetylcholinesterase inhibitor or memantine) within the past 6 weeks
8. Participants taking anticonvulsants, and other psychotropic medication (see exception below) that cannot be safely tapered and discontinued. The following psychotropic medications are allowed if they have been taken at a stable dose for at least 4 weeks prior to study entry: zopiclone, trazadone, or a benzodiazepine; gabapentin, pregabalin, duloxetine, venlafaxine, or low-dose tricyclic antidepressants if prescribed for chronic pain.
9. A pace-maker or other metal implants that would preclude safe use of tDCS.

MDD Group

Inclusion:

1. Age ≥ 60 (on day of randomization)

2. Meets DSM-IV criteria for one or more MDE(s)with:

   1. an offset of 2 months to 5 years from the screening visit date. It is not necessary for this (these) episode(s) to have received medical attention

      OR

   2. an offset of 5 years or more from the screening visit date. It is necessary that at least one MDE received medical attention (e.g., previously been on one or more antidepressant(s), saw a psychiatrist, primary care physician, or had a previous hospitalization). Also, the MDE must have occurred during the participant's adult life (i.e., at 18 years of age or older).

3. MADRS score of 10 or below

4. Willingness to provide informed consent

5. Availability of a study partner who has regular contact with the participant

6. Ability to read and communicate in English (with corrected vision and hearing, if needed)

Exclusion:

1. Meets DSM-IV criteria for Major Neurocognitive Disorder ("dementia")
2. Lifetime DSM-IV diagnosis of schizophrenia, bipolar disorder, or OCD
3. DSM-IV diagnosis of alcohol or other substances use disorder within the past 12 months.
4. High risk for suicide.
5. Significant neurological condition (e.g., stroke, seizure disorder, MS)
6. Unstable medical illness (e.g., uncontrolled diabetes mellitus or hypertension)
7. Participants taking anticonvulsants, and other psychotropic medication (see exception below) that cannot be safely tapered and discontinued. In addition to any antidepressant, the following psychotropic medications are allowed if they have been taken at a stable dose for at least 4 weeks prior to study entry: zopiclone, trazodone, or a benzodiazepine; and gabapentin or pregabalin if prescribed for chronic pain.
8. Having taken a cognitive enhancer (acetylcholinesterase inhibitor or memantine) within the past 6 weeks.
9. A pace-maker or other metal implants that would preclude safe use of tDCS.

Facilitator Group

Inclusion:

1. Willingness to provide informed consent

2. Ability to read and communicate in English (with corrected vision and hearing, if needed)

   Exclusion:

3. Physical or medical illness that prevents participant from learning or administering CR + tDCS, as determined by the research team