Memory Functions in Mild Alzheimer's Disease

A group of 20 cognitively intact younger participants (age 21-35), a group of 20 cognitively intact older participants (age 55+) and an age-matched group of 20 MCI/mild AD participants will be enrolled in the brain stimulation study with behavioral assessments at baseline and post-intervention. All participants will perform a laboratory-based memory task and an autobiographical memory task, followed by the autobiographical interview after the tACS intervention. Each participant will undergo three experimental sessions, applying 20-minute gamma tACS stimulation, theta tACS stimulation or an active sham (control) to the left angular gyrus. Before, during, and after the brain stimulation scalp high-density 257-channels EEG will be recorded to characterize and differentiate brain activity and regional interactions in the three independent groups.

Inclusion criteria

Healthy young participants:

• age 21-35
• without any cognitive impairment (based on the Montreal Cognitive Assessment: MoCA - in-person screening or Telephone Interview of Cognitive Status: TICS - phone screening)
• willing and capable to give informed consent for the participation in the study after it has been thoroughly explained able and willing to comply with all study requirements informed consent form (ICF) form was signed
• Understanding of the ICF will be assessed by asking the participant to answer the following three questions: 1) What is the purpose of this study? 2) What are the risks of study involvement? 3) If you decide to participate, are you allowed to withdraw from the study at any time? Answers will be recorded by study personnel on the "Assessment of Protocol Understanding" form . Insufficient understanding will be defined by one or more incorrect answers, as determined at the discretion of the investigator.

Healthy older participants:

• age 55+ without any cognitive impairment (based in MoCA or TICS)
• willing and capable to give informed consent for the participation in the study after it has been thoroughly explained able and willing to comply with all study requirements informed consent form was signed
• Understanding of the ICF will be assessed by asking the participant to answer the following three questions: 1) What is the purpose of this study? 2) What are the risks of study involvement? 3) If you decide to participate, are you allowed to withdraw from the study at any time? Answers will be recorded by study personnel on the "Assessment of Protocol Understanding" form. Insufficient understanding will be defined by one or more incorrect answers, as determined at the discretion of the investigator.

Older MCI/mild AD participants:

• age 55+
• who have been diagnosed with cognitive impairment (based in MoCA or TICS and Clinical Dementia Rating: CDR)
• willing and capable to give informed consent for the participation in the study after it has been thoroughly explained - note that to ensure this in the case for the MCI/AD participants, a cut off of MOCA score >18 will be applied
• able and willing to comply with all study requirements informed consent form was signed
• Understanding of the ICF will be assessed by asking the participant to answer the following three questions: 1) What is the purpose of this study? 2) What are the risks of study involvement? 3) If you decide to participate, are you allowed to withdraw from the study at any time? Answers will be recorded by study personnel on the "Assessment of Protocol Understanding" form. Insufficient understanding will be defined by one or more incorrect answers, as determined at the discretion of the investigator.

Exclusion criteria

Healthy young participants:

• potentially eligible individuals will complete the Telephone Interview of Cognitive Status (TICS) score of ≤31 or any cognitive impairment captured by the Montreal Cognitive Assessment (MoCA) - score < 26
• major psychiatric co-morbidity including major depressive disorder, schizophrenia or psychosis
• blindness or other disabilities that prevent task performance
• contraindications to tACS, as recorded on a standardized screening questionnaire, which include a reported seizure within the past two years, use of neuroactive drugs, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemaker, etc.), or the presence of any active dermatological condition, such as eczema, on the scalp

Healthy older participants:

• potentially eligible individuals will complete the Telephone Interview of Cognitive Status (TICS) with a score of ≤31 or any cognitive impairment captured by the Montreal Cognitive Assessment (MoCA) - score < 26
• major psychiatric co-morbidity including major depressive disorder, schizophrenia or psychosis
• blindness or other disabilities that prevent task performance
• contraindications to tACS, as recorded on a standardized screening questionnaire, which include a reported seizure within the past two years, use of neuroactive drugs, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemaker, etc.), or the presence of any active dermatological condition, such as eczema, on the scalp

Older MCI/mild AD participants:

• cut off of MOCA score <18 will be applied
• major psychiatric co-morbidity including major depressive disorder, schizophrenia or psychosis
• blindness or other disabilities that prevent task performance
• contraindications to tACS, as recorded on a standardized screening questionnaire, which include a reported seizure within the past two years, use of neuro-active drugs, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemaker, etc.), or the presence of any active dermatological condition, such as eczema, on the scalp