Gamma-Band Transcranial Magnetic Stimulation in Rehabilitation of Amnestic Mild Cognitive Impairment and Alzheimer’s Disease
Date Issued
May 2023
Author(s)
Advisor
Abstract
Alzheimer’s disease (AD) is a slowly progressive neurodegenerative disorder and the
most common cause of dementia worldwide. Many pathogenic mechanisms and
hypotheses have been proposed to explain AD pathology, and scientific knowledge has
increased enormously over the last decades. However, to date, clinical trials targeting
these mechanisms have not succeeded in identifying effective methods to treat or
reverse the disease. AD pathogenesis has recently been explored from different
perspectives, offering new insights into the potential treatments of AD. Among these,
the investigation of gamma oscillations and their potential therapeutic role has signified
a new and promising era in AD research.
The aim of this thesis was to combine the most recent scientific findings to develop a
novel, gamma-band transcranial magnetic stimulation (TMS) protocol and investigate
its efficacy in mitigating cognitive dysfunction in patients with amnestic mild cognitive
impairment (MCI) and mild-to-moderate AD. On that basis the thesis is comprised by
three main study pillars, being the neurophysiological, normative, and experimental.
Initially, a novel 40 Hz TMS protocol was developed and applied over the motor cortex
of healthy participants. Its safety and aftereffects on cortical excitability were
evaluated. The results indicated that stimulation was safe, tolerable, and generated a
suppressive effect that outlasted the stimulation period. Then, the first standardized
Cypriot word pool, a list of 2,850 words, was created and used for the development of
alternative and equally difficult neuropsychological tools. Finally, a single-case,
randomized, concurrent multiple baseline design across eight cases was employed.
Patients received daily 40 Hz TMS treatment sessions for 2 weeks bilaterally to the
precuneus. The analyses indicated a significant improvement in all patients’ global
cognition, while an identical profile of significant improvement was evident in patients’
neuropsychiatric symptoms. In general, a wide effect on patients’ cognitive function
was observed accompanied by a significant improvement in their quality of life. This
study offers preliminary evidence regarding the efficacy of gamma-band TMS as an
effective and safe non-invasive technique in MCI and AD neurorehabilitation.
most common cause of dementia worldwide. Many pathogenic mechanisms and
hypotheses have been proposed to explain AD pathology, and scientific knowledge has
increased enormously over the last decades. However, to date, clinical trials targeting
these mechanisms have not succeeded in identifying effective methods to treat or
reverse the disease. AD pathogenesis has recently been explored from different
perspectives, offering new insights into the potential treatments of AD. Among these,
the investigation of gamma oscillations and their potential therapeutic role has signified
a new and promising era in AD research.
The aim of this thesis was to combine the most recent scientific findings to develop a
novel, gamma-band transcranial magnetic stimulation (TMS) protocol and investigate
its efficacy in mitigating cognitive dysfunction in patients with amnestic mild cognitive
impairment (MCI) and mild-to-moderate AD. On that basis the thesis is comprised by
three main study pillars, being the neurophysiological, normative, and experimental.
Initially, a novel 40 Hz TMS protocol was developed and applied over the motor cortex
of healthy participants. Its safety and aftereffects on cortical excitability were
evaluated. The results indicated that stimulation was safe, tolerable, and generated a
suppressive effect that outlasted the stimulation period. Then, the first standardized
Cypriot word pool, a list of 2,850 words, was created and used for the development of
alternative and equally difficult neuropsychological tools. Finally, a single-case,
randomized, concurrent multiple baseline design across eight cases was employed.
Patients received daily 40 Hz TMS treatment sessions for 2 weeks bilaterally to the
precuneus. The analyses indicated a significant improvement in all patients’ global
cognition, while an identical profile of significant improvement was evident in patients’
neuropsychiatric symptoms. In general, a wide effect on patients’ cognitive function
was observed accompanied by a significant improvement in their quality of life. This
study offers preliminary evidence regarding the efficacy of gamma-band TMS as an
effective and safe non-invasive technique in MCI and AD neurorehabilitation.
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