Therapeutic noninvasive brain stimulation in Alzheimer's disease and related dementias

Buss, Stephanie S.; Fried, Peter J.; Pascual‐Leone, Álvaro

doi:10.1097/wco.0000000000000669

Cited by 54 publications

(44 citation statements)

References 67 publications

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“…Much larger samples, offering increased statistical power, are needed to accurately estimate effect size and enhance reproducibility (Button et al, 2013). As noted in the FDA review cited earlier and in previous reports (Buss et al, 2019;Koch et al, 2019), properly designed, larger, and longer trials are needed to address unresolved issues in the use of rTMS as a therapeutic treatment for AD.…”

Section: Challenges In Assessing Rtms Effects In Admentioning

confidence: 99%

Transcranial Magnetic Stimulation in Alzheimer’s Disease: Are We Ready?

Weiler

Stieger

Long

et al. 2019

eNeuro

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Transcranial magnetic stimulation (TMS) is among a growing family of noninvasive brain stimulation techniques being developed to treat multiple neurocognitive disorders, including Alzheimer's disease (AD). Although small clinical trials in AD have reported positive effects on cognitive outcome measures, significant knowledge gaps remain, and little attention has been directed at examining the potential influence of TMS on AD pathogenesis. Our review briefly outlines some of the proposed neurobiological mechanisms of TMS benefits in AD, with particular emphasis on the modulatory effects on excitatory/inhibitory balance. On the basis of converging evidence from multiple fields, we caution that TMS therapeutic protocols established in young adults may have unexpected detrimental effects in older individuals or in the brain compromised by AD pathology. Our review surveys clinical studies of TMS in AD alongside basic research as a guide for moving this important area of work forward toward effective treatment development.

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Section: Challenges In Assessing Rtms Effects In Admentioning

confidence: 99%

Transcranial Magnetic Stimulation in Alzheimer’s Disease: Are We Ready?

Weiler

Stieger

Long

et al. 2019

eNeuro

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“…More recently, biophysical factors have been suggested to induce neurogenesis. Those include ultrasound, magnetic, and deep brain electrical stimulation [25][26][27][28][29][30][31][32][33]. Ultrasound stimulation is non-invasive and can induce hippocampal neurogenesis in healthy mice [29].…”

Section: Introductionmentioning

confidence: 99%

“…Those include ultrasound, magnetic, and deep brain electrical stimulation [25][26][27][28][29][30][31][32][33]. Ultrasound stimulation is non-invasive and can induce hippocampal neurogenesis in healthy mice [29]. Deep brain electrical stimulation enhances metabolism, improves memory and behavior, and induces neurogenesis in the healthy and diseased rodent brain [34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

“…For example, regular intense exercise is difficult to implement for patients (most often unable to do so independently), while stem cell therapy involves invasively injecting cells into the brain. Ultrasound compromises the blood-brain barrier permeability via injection of microbubbles [29], which carries the risk of tissue damage and behavioral decline [38]. Deep brain stimulation requires electrodes inside the brain, which induces injuries to the brain.…”

Section: Introductionmentioning

confidence: 99%

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Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease

et al. 2020

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Background: Neurogenesis is significantly impaired in the brains of both human patients and experimental animal models of Alzheimer's disease (AD). Although deep brain stimulation promotes neurogenesis, it is an invasive technique that may damage neural circuitry along the path of the electrode. To circumvent this problem, we assessed whether intracranial electrical stimulation to the brain affects neurogenesis in a mouse model of Alzheimer's disease (5xFAD). Methods and results: We used Ki67, Nestin, and doublecortin (DCX) as markers and determined that neurogenesis in both the subventricular zone (SVZ) and hippocampus were significantly reduced in the brains of 4-month-old 5xFAD mice. Guided by a finite element method (FEM) computer simulation to approximately estimate current and electric field in the mouse brain, electrodes were positioned on the skull that were likely to deliver stimulation to the SVZ and hippocampus. After a 4-week program of 40-Hz intracranial alternating current stimulation (iACS), neurogenesis indicated by expression of Ki67, Nestin, and DCX in both the SVZ and hippocampus were significantly increased compared to 5xFAD mice who received sham stimulation. The magnitude of neurogenesis was close to the wild-type (WT) age-matched unmanipulated controls. Conclusion: Our results suggest that iACS is a promising, less invasive technique capable of effectively stimulating the SVZ and hippocampus regions in the mouse brain. Importantly, iACS can significantly boost neurogenesis in the brain and offers a potential treatment for AD.

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“…A causative treatment for AD and other degenerative dementias is yet to be discovered, with the available treatment options offering only symptomatic benefits [5][6][7]. To date, the medications approved for the treatment of AD include the acetylcholinesterase (AChE) inhibitors (tacrine, donepezil, rivastigmine, and galantamine) and the memantine, which is a N-methyl-D-aspartate (NMDA) glutamate receptor antagonist.…”

Section: Introductionmentioning

confidence: 99%

Acetyl-L-Carnitine in Dementia and Other Cognitive Disorders: A Critical Update

Pennisi

Lanza

Cantone³

et al. 2020

Nutrients

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Several studies explored the effects of acetyl-L-carnitine (ALC) in dementia, suggesting a role in slowing down cognitive decline. Nevertheless, in 2003 a systematic review concluded there was insufficient evidence to recommend a clinical use, although a meta-analysis in the same year showed a significant advantage for ALC for clinical scales and psychometric tests. Since then, other studies have been published; however, a critical review is still lacking. We provide an update of the studies on ALC in primary and secondary dementia, highlighting the current limitations and translational implications. Overall, the role of ALC in dementia is still under debate. The underlying mechanisms may include restoring of cell membranes and synaptic functioning, enhancing cholinergic activity, promoting mitochondrial energy metabolism, protecting against toxins, and exerting neurotrophic effects. The effects of ALC on the gut–liver–brain axis seem to identify the category of patients in which the new insights contribute most to the mechanisms of action of ALC, likely being the liver metabolism and the improvement of hepatic detoxifying mechanisms the primary targets. In this framework, our research group has dealt with this topic, focusing on the ALC-related cross-talk mechanisms. Further studies with homogeneous sample and longitudinal assessment are needed before a systematic clinical application.

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Therapeutic noninvasive brain stimulation in Alzheimer's disease and related dementias

Cited by 54 publications

References 67 publications

Transcranial Magnetic Stimulation in Alzheimer’s Disease: Are We Ready?

Transcranial Magnetic Stimulation in Alzheimer’s Disease: Are We Ready?

Intracranial alternating current stimulation facilitates neurogenesis in a mouse model of Alzheimer’s disease

Acetyl-L-Carnitine in Dementia and Other Cognitive Disorders: A Critical Update

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