Effects of a combined transcranial magnetic stimulation (TMS) and cognitive training intervention in patients with Alzheimer's disease

Sabbagh, Marwan N.; Sadowsky, Carl; Tousi, Babak; Agronin, Marc E.; Alva, Gustavo; Armon, Carmel; Bernick, Charles; Keegan, Andrew P.; Karantzoulis, Stella; Baror, Eyal; Ploznik, Moran; Pascual‐Leone, Álvaro

doi:10.1016/j.jalz.2019.08.197

Cited by 109 publications

(99 citation statements)

References 45 publications

(91 reference statements)

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“…In our previous clinical AD study with TPS, the procedure was well tolerated and after treatment, memory performance improved for up to 3 months. These results parallel those of another brain stimulation study investigating the long-term effects of TMS as a treatment for AD [22]. Although these are the very first in-vivo data on ultrasound related brain-morphological changes, several limitations of the study have to be considered.…”

Section: Discussionsupporting

confidence: 76%

Transcranial ultrasound pulse stimulation reduces cortical atrophy in Alzheimer's patients: a follow-up study

Popescu¹,

Pernet²,

Beisteiner³

2020

Preprint

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INTRODUCTION: Ultrasound for the brain is a revolutionary therapeutic concept. The first clinical data indicate that 2-4 weeks of therapy with Transcranial Pulse Stimulation improve functional networks and cognitive performance of Alzheimer’s disease (AD) patients for up to 3 months. No data currently exist on possible benefits concerning brain morphology, concerning namely the cortical atrophy characteristic of AD. METHODS: We performed a pre-/post-therapy analysis of cortical thickness in a group of N=17 Alzheimer’s patients. RESULTS: We found a significant correlation between neuropsychological improvement and cortical thickness increase in AD-critical brain areas. DISCUSSION: AD patients who benefit from TPS appear to reduce cortical atrophy within the default mode network in particular.

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Section: Discussionsupporting

confidence: 76%

Transcranial ultrasound pulse stimulation reduces cortical atrophy in Alzheimer's patients: a follow-up study

Popescu¹,

Pernet²,

Beisteiner³

2020

Preprint

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“…Although rTMS has been used to treat AD in clinic, specific treatment schemes are not unified, and the mechanism is unclear. Thus, the research on rTMS to treat AD needs further investigation (Alcalá‐Lozano et al., 2018; Sabbagh et al., 2019; Turriziani et al., 2019). Recent studies have focused on the cognitive impairment of rTMS in AD model mice or patients, and there are few reports on the characteristic pathological changes and the mechanism of AD lesions (Huang et al., 2017; Ma et al., 2017).…”

Section: Discussionmentioning

confidence: 99%

“…As a noninvasive intervention, rTMS has developed into a promising choice for therapy and rehabilitation of neuropsychiatric diseases (Brunelin et al., 2014; Etoh et al., 2019; Hirakawa et al., 2018; Sabbagh et al., 2019). Both low‐frequency and high‐frequency rTMS have been proved to improve the cognitive function and synaptic plasticity of AD model in mice (Cotelli et al., 2011).…”

Section: Introductionmentioning

confidence: 99%

High‐frequency transcranial magnetic stimulation protects APP/PS1 mice against Alzheimer’s disease progress by reducing APOE and enhancing autophagy

2020

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Introduction The repetitive transcranial magnetic stimulation (rTMS) has clinically wide application prospect of psychiatry and neuroscience, for its painless, noninvasive, and high efficiency. So far, rTMS has been used in the treatment of Alzheimer's disease (AD) but the underlying mechanism is not clear. Methods and Results The APP/PS1 mice at 3‐month‐old were treated by 5 Hz high‐frequency (HF) rTMS for two weeks. After rTMS treatment, the AD‐like cognitive impairments of APP/PS1 mice were investigated subsequently, and molecular mechanisms underlying was further explored. The study showed that the 2‐week rTMS at 5Hz frequency improved cognitive impairments and AD‐like pathology (including a decrease in p‐Tau, APP, Aβ, and PP2A expression) of APP/PS1 mice. Although BDNF‐TrkB signaling was significantly enhanced, no differences of SYN, PSD95 and p‐AKT were observed in the brain of APP/PS1 mice. On the contrary, the LC3Ⅱ/LC3Ⅰ ratio was elevated with a significant reduction of ApoE and p62 in mice. Conclusions rTMS exerts a potentially protective role in the prevention and treatment of AD by reducing ApoE expression and promoting autophagic flux, which provides a new insight into the mechanism of rTMS.

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“…Positive effects of Aβ immunotherapy in mice models have been reported [ 31 , 32 , 33 , 35 ], but, unfortunately, human clinical trials have not yet been successful in passing phase 3 [ 30 ]. There are also studies that suggest that physical exercise decreases synaptic dysfunction in AD mice models [ 62 ] and the positive effect of cognitive stimulation to delay the progression of the pathology [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Cognitive Impairment in the 3xTg-AD Mouse Model of Alzheimer’s Disease is Affected by Aβ-ImmunoTherapy and Cognitive Stimulation

et al. 2020

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Clinical symptoms of Alzheimer’s Disease (AD) include behavioral alterations and cognitive impairment. These functional phenotypes early occur in triple-transgenic (3xTg-AD) mice. Specifically, behavioral alterations are first detected when mice are at around 2.5 months old and cognitive impairment in between 3- and 5-month-old mice. In this work, the effect of chronic Aβ-immunotherapy on behavioral and cognitive abilities was tested by monthly administering the antibody fragment scFv-h3D6 to 3xTg-AD female mice from 5 to 9 months of age. An untreated group was used as a reference, as well as to attain some information on the effect of training during the longitudinal study. Behavioral and psychological symptoms of dementia (BPSD)-like symptoms were already evident in 5-month-old mice, in the form of neophobia and anxious-like behavior. The exploratory activity decreased over the longitudinal study, not only for 3xTgAD mice but also for the corresponding non-transgenic mice (NTg). Learning abilities of 3xTg-AD mice were not seriously compromised but an impairment in long-term spatial memory was evident at 5 months of age. Interestingly, scFv-h3D6-treatment affected the cognitive impairment displayed by 5-month-old 3xTg-AD mice. It is worth noting that training also reduced cognitive impairment of 3xTg-AD mice over the longitudinal study, suggesting that to properly quantify the isolated therapeutic potential of any drug on cognition using this model it is convenient to perform a prompt, age-matched study rather than a longitudinal study. In addition, a combination of both training and Aβ-immunotherapy could constitute a possible approach to treat Alzheimer’s disease.

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Effects of a combined transcranial magnetic stimulation (TMS) and cognitive training intervention in patients with Alzheimer's disease

Cited by 109 publications

References 45 publications

Transcranial ultrasound pulse stimulation reduces cortical atrophy in Alzheimer's patients: a follow-up study

Transcranial ultrasound pulse stimulation reduces cortical atrophy in Alzheimer's patients: a follow-up study

High‐frequency transcranial magnetic stimulation protects APP/PS1 mice against Alzheimer’s disease progress by reducing APOE and enhancing autophagy

Cognitive Impairment in the 3xTg-AD Mouse Model of Alzheimer’s Disease is Affected by Aβ-ImmunoTherapy and Cognitive Stimulation

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