Repetitive Transcranial Magnetic Stimulation for Dementia

NIH RePORTER · VA · I21 · · view on reporter.nih.gov ↗

Abstract

 DESCRIPTION (provided by applicant): The purpose of this study is to evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a treatment for Alzheimer's disease (AD). The primary hypothesis is that rTMS applied to the dorsolateral prefrontal cortex will lead to improved memory, language and executive function compared to patients who receive a sham, control treatment. The improvement is defined as having higher performance on the California Verbal Learning Test (CVLT-II). Secondary Hypothesis are that 1)rTMS- will lead to higher performance on secondary cognitive measures relating to executive function and naming compared to performance by participants in the sham treatment group at the termination of treatment; and that 2) rTMS-induced memory improvement parallels changes in BDNF levels after treatment. Alzheimer's disease (AD) is extremely common among older adults, and is the most frequent cause of dementia in the general population (Kukull et al., 2002; National Institute of Health, 2010). Current treatments of AD are limited in their effectiveness and do not halt the progress of the disease. rTMS has been found to be effective in several conditions related to AD, and there is emerging evidence to suggest that it may be effective in treating AD (Bentwich et al., 2011; Ahmed et al., 2012, Rabey et al., 2013, Tezzon et al., 2014). Studies show that rTMS modifies the neuronal networking function (Hamidi et al., 2010; van der Werf et al., 2010). Although the exact mechanism by which rTMS causes improvement in cognitive function is unknown, it has been observed that rTMS reversed a decline in brain-derived neurotrophic factor (BDNF), lead to up-regulated NMDA-receptor expression in the hippocampus in mice (Tan et al., 2013) ), and caused increased level of BDNF in chronic pain patients (Dall'Agnol et al., 2014). This study aims to obtain better understanding how rTMS affect BDNF levels and how the change in BDNF level corresponds to cognitive improvement. The literature on rTMS and AD includes several studies, but all have significant limitations. First, studies have not involved comprehensive memory assessment (Bentwich et al., 2011; Cotelli et al., 2006, 2008, 2011), despite memory impairment being a primary deficit in AD (McKhann et al., 2011). Second, some studies have not included a control group or controlled for practice effects on cognitive testing. Third, studie have been limited by small sample sizes, limiting the power to detect effects of rTMS on cognitive functioning. Lastly, no studies have been completed with Veteran patients. This study will include 52 Veterans with a diagnosis of Mild Cognitive Impairment due to AD or Dementia due to AD over a period of two years. To account for an estimated 20% attrition rate, we will recruit an additional 10 participants to ensure a sufficient sample size and power to complete analyses (final sample n = 62). This double-blinded, randomized clinical trial will...

Key facts

NIH application ID
9950857
Project number
5I21RX001889-05
Recipient
VETERANS ADMIN PALO ALTO HEALTH CARE SYS
Principal Investigator
Jauhtai J. Cheng
Activity code
I21
Funding institute
VA
Fiscal year
2020
Award amount
Award type
5
Project period
2016-01-01 → 2020-01-31