Electrical brain stimulation in different variants of primary progressive aphasia: A randomized clinical trial

Kyrana Tsapkini, Kimberly T Webster, Bronte N Ficek, John E Desmond, Chiadi U Onyike, Brenda Rapp, Constantine E Frangakis, Argye E Hillis, Kyrana Tsapkini, Kimberly T Webster, Bronte N Ficek, John E Desmond, Chiadi U Onyike, Brenda Rapp, Constantine E Frangakis, Argye E Hillis

Abstract

Introduction: Transcranial direct current stimulation (tDCS) has been recently shown to improve language outcomes in primary progressive aphasia (PPA) but most studies are small and the influence of PPA variant is unknown.

Methods: Thirty-six patients with PPA participated in a randomized, sham-controlled, double-blind, within-subject crossover design for 15 daily sessions of stimulation coupled with written naming/spelling therapy. Outcome measures were letter accuracy of treated and untreated words immediately after and at 2 weeks and 2 months posttreatment.

Results: tDCS treatment was more effective than sham: gains for treated words were maintained 2 months posttreatment; gains from tDCS also generalized to untreated words and were sustained 2 months posttreatment. Different effects were obtained for each PPA variant, with no tDCS advantage for semantic variant PPA.

Discussion: The study supports using tDCS as an adjunct to written language interventions in individuals with logopenic or nonfluent/agrammatic PPA seeking compensatory treatments in clinical settings.

Keywords: Alzheimer's disease; Dementia; Frontotemporal dementia; Language; Naming; Primary progressive aphasia; Spelling; Treatment; lvPPA; nfvPPA; svPPA.

Figures

Fig. 1
Fig. 1
Participant flow chart and time course of interventions and evaluations for the two groups of participants in the crossover design.
Fig. 2
Fig. 2
(Top panel) Treated items for all 36 PPA participants. (Bottom panel) Untreated items for all 36 PPA participants. Phase 1 of treatment is on the left and phase 2 is on the right. Blue lines, tDCS effects; red lines, sham effects. The graphs depict the absolute therapy gain in terms of the percentage of change from baseline condition. Bars at each time point represent 1 standard deviation from the mean. The numbers at each follow-up time indicate the number of participants at that time. Average effects and P values of the GEE statistic are calculated in the last column of the tables. Abbreviations: GEE, generalized estimating equation; PPA, primary progressive aphasia; tDCS, transcranial direct current stimulation.
Fig. 3
Fig. 3
(Top panel) Treated items for lvPPA participants. (Bottom panel) Untreated items for lvPPA participants. Blue lines, tDCS effects; red lines, sham effects. Phase 1 of treatment is on the left and phase 2 is on the right. The graphs depict the absolute therapy gain in terms of the percentage of change from baseline condition. Bars at each time point represent 1 standard deviation from the mean. The numbers at each follow-up time indicate the number of participants at that time. Average effects and P values of the GEE statistic are calculated in the last column of the tables. Abbreviations: GEE, generalized estimating equation; lvPPA, logopenic variant primary progressive aphasia; tDCS, transcranial direct current stimulation.
Fig. 4
Fig. 4
(Top panel) Treated items for nfvPPA participants. (Bottom panel) Untreated items for nfvPPA participants. Phase 1 of treatment is on the left and phase 2 is on the right. Blue lines, tDCS effects; red lines, sham effects. The graphs depict the absolute therapy gain in terms of the percentage of change from baseline condition. Bars at each time point represent 1 standard deviation from the mean. The numbers at each follow-up time indicate the number of participants at that time. Average effects and P values of the GEE statistic are calculated in the last column of the tables. Abbreviations: GEE, generalized estimating equation; nfvPPA, nonfluent/agrammatic primary progressive aphasia; tDCS, transcranial direct current stimulation.
Fig. 5
Fig. 5
(Top panel) Treated items for svPPA participants. (Bottom panel) Untreated items for svPPA participants. Phase 1 of treatment is on the left and phase 2 is on the right. Blue lines, tDCS effects; red lines, sham effects. The graphs depict the absolute therapy gain in terms of the percentage of change from baseline condition. Bars at each time point represent 1 standard deviation from the mean. The numbers at each follow-up time indicate the number of participants at that time. Average effects and P values of the GEE statistic are calculated in the last column of the tables. Abbreviations: GEE, generalized estimating equation; svPPA, semantic variant primary progressive aphasia; tDCS, transcranial direct current stimulation.
Supplementary Fig. 1
Supplementary Fig. 1
Simulation of current flow over the left IFG as targeted by 5 × 5 cm sponges. (Image courtesy of Dr. Marom Bikson).

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