Diminishing accelerated long-term forgetting in mild cognitive impairment: Study protocol for a prospective, double-blind, placebo-controlled, randomized controlled trial

Katherine S Adcock, Brian Lawlor, Ian H Robertson, Sven Vanneste, Katherine S Adcock, Brian Lawlor, Ian H Robertson, Sven Vanneste

Abstract

Background: Harnessing the lifelong potential of the human brain for neuroplasticity may serve to maintain the viability of neural structures and postpone the onset of cognitive decline. The absence of effective pharmacological interventions to counter memory decline has encouraged scientists to test the possibility that noninvasive electrical stimulation may serve as an additional tool to improve memory abilities.Previous research showed that electrical stimulation of the greater occipital nerve enhances memory recall performance in young and older healthy subjects. This study aims to extend these findings to determine the effect of transcutaneous electrical stimulation of the greater occipital nerve on the improvement of episodic memory in individuals with amnestic Mild Cognitive Impairment (aMCI).

Methods/design: This study is a prospective, double-blind, placebo-controlled, randomized parallel-group study. A total of 100 individuals with a diagnosis of aMCI according to NIA/AA will be recruited. Participants will be randomly assigned to one of four groups. One group will receive active non-invasive transcutaneous electrical stimulation of greater occipital nerve (NITESGON), while three groups will serve as controls (i.e., sham NITESGON, active NITESGON with local anesthesia, and active NITESGON on the C5/C6 nerve). The primary outcome, i.e., memory recall, will be determined by a word association task, and will be recorded at baseline, 7 days after NITESGON, and 28 days after NITESGON. The secondary outcome is neurophysiological changes determined by resting state EEG and will be assessed immediately before and after NITESGON.

Discussion: The results will add new insights into improving episodic memory in individuals with aMCI.

Trial registration: #NCT05289804 (clinicaltrial.gov).

Protocol approval id: #SPREC102021-23 (Ethics Committee at Trinity College Dublin, School of Psychology).

Keywords: Amnestic mild cognitive impairment; Electrical stimulation; Episodic memory; Greater occipital nerve; Mild Alzheimer's disease.

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

© 2022 The Authors.

Figures

Fig. 1
Fig. 1
Participant flow through study.

References

    1. Lindenberger U. Human cognitive aging: corriger la fortune? Science. 2014;346(6209):572–578.
    1. Langa K.M., Levine D.A. The diagnosis and management of mild cognitive impairment: a clinical review. JAMA. 2014;312(23):2551–2561.
    1. Yau W.W., et al. Longitudinal assessment of neuroimaging and clinical markers in autosomal dominant Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2015;14(8):804–813.
    1. Dudai Y., Karni A., Born J. The consolidation and transformation of memory. Neuron. 2015;88(1):20–32.
    1. Kitamura T., et al. Engrams and circuits crucial for systems consolidation of a memory. Science. 2017;356(6333):73–78.
    1. Sara S.J. The locus coeruleus and noradrenergic modulation of cognition. Nat. Rev. Neurosci. 2009;10(3):211–223.
    1. Bondareff W., et al. Neuronal degeneration in locus ceruleus and cortical correlates of Alzheimer disease. Alzheimer Dis. Assoc. Disord. 1987;1(4):256–262.
    1. German D.C., et al. Disease-specific patterns of locus coeruleus cell loss. Ann. Neurol. 1992;32(5):667–676.
    1. Yates C.M., et al. Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down's syndrome. Brain Res. 1983;280(1):119–126.
    1. Chan-Palay V., Asan E. Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson's disease with and without dementia and depression. J. Comp. Neurol. 1989;287(3):373–392.
    1. Haglund M., Sjobeck M., Englund E. Locus ceruleus degeneration is ubiquitous in Alzheimer's disease: possible implications for diagnosis and treatment. Neuropathology. 2006;26(6):528–532.
    1. Lyness S.A., Zarow C., Chui H.C. Neuron loss in key cholinergic and aminergic nuclei in Alzheimer disease: a meta-analysis. Neurobiol. Aging. 2003;24(1):1–23.
    1. Zarow C., et al. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch. Neurol. 2003;60(3):337–341.
    1. Takahashi J., et al. Detection of changes in the locus coeruleus in patients with mild cognitive impairment and Alzheimer's disease: high-resolution fast spin-echo T1-weighted imaging. Geriatr. Gerontol. Int. 2015;15(3):334–340.
    1. Vanneste S., et al. The peripheral effect of direct current stimulation on brain circuits involving memory. Sci. Adv. 2020;6(45)
    1. Luckey A.M., et al. Greater occipital nerve stimulation boosts associative memory in older individuals: a randomized trial. Neurorehabilitation Neural Repair. 2020;34(11):1020–1029.
    1. Albert M.S., et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):270–279.
    1. Petersen R.C. Mild cognitive impairment as a diagnostic entity. J. Intern. Med. 2004;256(3):183–194.
    1. Kumar M., Chawla R., Goyal M. Topical anesthesia. J. Anaesthesiol. Clin. Pharmacol. 2015;31(4):450–456.
    1. Karpicke J.D., Roediger H.L., 3rd The critical importance of retrieval for learning. Science. 2008;319(5865):966–968.
    1. Brunoni A.R., et al. A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Int. J. Neuropsychopharmacol. 2011;14(8):1133–1145.
    1. Lefaucheur J.P., et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS) Clin. Neurophysiol. 2017;128(1):56–92.
    1. Bikson M., et al. Safety of transcranial direct current stimulation: evidence based update 2016. Brain Stimul. 2016;9(5):641–661.
    1. Matsumoto H., Ugawa Y. Adverse events of tDCS and tACS: a review. Clin Neurophysiol Pract. 2017;2:19–25.
    1. Poreisz C., et al. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res. Bull. 2007;72(4–6):208–214.
    1. Luckey A.M., et al. Potential role for peripheral nerve stimulation on learning and long-term memory: a comparison of alternating and direct current stimulations. Brain Stimul. 2022;15(3):536–545.
    1. Pascual-Marqui R. 2007. Discrete, 3D Distributed, Linear Imaging Methods of Electric Neuronal Activity. Part 1: Exact, Zero Error Localization.
    1. Nichols T.E., Holmes A.P. Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum. Brain Mapp. 2002;15(1):1–25.
    1. Weston P.S.J., et al. Accelerated long-term forgetting in presymptomatic autosomal dominant Alzheimer's disease: a cross-sectional study. Lancet Neurol. 2018;17(2):123–132.
    1. Walsh C.M., et al. Memory consolidation in aging and MCI after 1 week. Neuropsychology. 2014;28(2):273–280.
    1. Braak H., Del Tredici K. Alzheimer's pathogenesis: is there neuron-to-neuron propagation? Acta Neuropathol. 2011;121(5):589–595.
    1. Braak H., Del Tredici K. The pathological process underlying Alzheimer's disease in individuals under thirty. Acta Neuropathol. 2011;121(2):171–181.
    1. Grudzien A., et al. Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease. Neurobiol. Aging. 2007;28(3):327–335.

Source: PubMed

3
Subscribe