Enhancing Working Memory in Patients With Early Alzheimer's Disease Through the Use of rTMS

Specific aim 1: To assess working memory in participants with Alzheimer's disease (AD) and its change in response to a 4-week course of bilateral rTMS of DLPFC. Hypothesis 1a: Compared to healthy individuals, participants with AD will be impaired on the N-back task. Hypothesis 1b: Compared to sham rTMS, active rTMS will result in improvement on the N-back task in participants with AD at 1 week and 4 weeks after the treatment. Specific aim 2: To assess DLPFC theta-gamma coupling during working memory performance in AD and its change in response to a 4-week course of bilateral rTMS of DLPFC. Hypothesis 2a: Compared to healthy individuals, participants with AD will be impaired on DLPFC theta-gamma coupling during the N-back task. Hypothesis 2b \& 2c: Compared to sham rTMS, active rTMS will result in improvement in DLPFC theta-gamma coupling during the N-back task in participants with AD at 1 week and 4 weeks after the treatment. Specific aim 3: To assess DLPFC neuroplasticity using PAS in participants with AD and its change in response to a 4-week course of bilateral rTMS. Hypothesis 3a: Compared to healthy individuals, participants with AD will be impaired on PAS-induced neuroplasticity. Hypothesis 3b: Compared to sham rTMS, active rTMS will result in improvement on PAS-induced neuroplasticity in participants with AD at 1 week and 4 weeks after the treatment. Specific aim 4: To assess change in working memory, theta gamma coupling and DLPFC neuroplasticity at 6 months after the course of bilateral rTMS. Hypothesis 4: Compared to sham rTMS, active rTMS group will perform better on measures of working memory, theta gamma coupling and PAS- induced DLPFC neuroplasticity 6 months after the course of rTMS. Specific aim 5: To assess the change in general cognitive function at 4 weeks and 6 months after the course of bilateral rTMS. Hypothesis 5: Compared to sham rTMS, active rTMS group will perform better on measures of general cognitive function at 4 weeks and 6 months after the course of rTMS. Specific Aim 6: To assess insight in AD at baseline and any change in insight at 4 week and 6 month post rTMS follow up. H6: Participants with AD will have impaired insight into illness and cognitive function and they will experience improved insight at 4 week and 6 month follow up points. Specific Aim 7: To validate a new scale for insight in AD , 'The Scale to Assess Anosognosia in Neurocognitive Disorders' (SAND) for its ability to assess insight at baseline and any change at 4 weeks and 6 month follow up points. H7: In participants with AD, SAND will be able to assess insight into illness and cognitive function at baseline, and will be able to detect change in insight at follow up points.