Alzheimer's Disease Clinical Trial
Official title:
Enhancing Working Memory in Patients With Early Alzheimer's Disease Through the Enhancement of Dorsolateral Prefrontal Cortex Neuroplasticity: A TMS-EEG Study
In this study the investigators aim at assessing and then enhancing neuroplasticity in the dorsolateral prefrontal cortex (DLPFC) and working memory - a key function of DLPFC - in patients with mild Alzheimer's disease (AD). The investigators will use Paired Associative Stimulation (PAS) paradigm to measure neuroplasticity and then a 4-week course of high-frequency repetitive Transcranial Magnetic Stimulation (rTMS) to the DLPFC to enhance cognitive function. Clinical and cognitive assessments will be done at baseline, one week, one month and 6 months after the rTMS course. Healthy controls will also be enrolled to carry out baseline cognitive assessments and a baseline measurement of neuroplasticity.
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.
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