Is Aphasia Treatment Beneficial for the Elderly? A Review of Recent Evidence

Abstract

Purpose:

We review recent literature regarding aphasia therapy in the elderly. Relevant articles from the last 5 years were identified to determine whether or not there is evidence to support that various therapeutic approaches can have a positive effect on post-stroke aphasia in the elderly.

Recent findings:

There were no studies examining the effects of aphasia therapy specifically in the elderly within the timeframe searched. Therefore, we briefly summarize findings from 50 relevant studies that included large proportions of participants with post-stroke aphasia above the age of 65. A variety of behavioral and neuromodulation therapies are reported.

Summary:

We found ample evidence suggesting that a variety of behavioral and neuromodulatory therapeutic approaches can benefit elderly individuals with post-stroke aphasia.

Introduction

Stroke is a leading cause of long-term disability [1], disproportionately affecting older adults; 70–77% of stroke patients are over 65 [2, 3], and about 17% are over 85 years-old [4]. Very elderly patients have higher disability and receive less evidenced-based care [5, 6]. The greatest expected increase in stroke prevalence is among those over age 75 [7].

Approximately 20–30% of strokes result in aphasia (neurogenic language impairment) [8, 9], and about 19% of stroke survivors over 65 continue to have aphasia at 6 months post stroke [10]. Aphasia can manifest as difficulty with comprehension, production, or both, in any modality (i.e., spoken language, reading/writing, or gesture). An individual’s independence can be significantly impacted by aphasia [11]. Communication is an essential part of human connection and is critical for maximizing and maintaining quality of life. Thus, remediation of aphasia after stroke aims to reduce language impairment and/or increase functional communication, participation, and quality of life and reduce care burden. Stroke survivors with aphasia are typically older than those without aphasia [9, 12], so it is particularly important to understand the role of aphasia treatment in the older population.

In this article we review the current literature regarding aphasia therapy in the elderly. Relevant publications within the past 5 years were identified by searching for the general terms elderly, aphasia, and therapy/rehabilitation in the following databases: PubMed, Medline, ProQuest, ERIC and Google Scholar. Search results were limited to English language publications from 2015 through March 19, 2020.

Over 750 studies were screened for duplications and relevance (i.e., reports on the effects of treatment for elderly persons with aphasia). There were no studies examining the effects of aphasia therapy explicitly in the elderly within the timeframe searched. Therefore, we focused on higher quality treatment evidence that included relatively large proportions of participants above the age of 65 to draw meaningful conclusions (e.g., a single participant above 65 in a group of 20 was not considered to provide meaningful evidence pertinent to the older adult population and was therefore excluded). Likewise, small n or case studies are difficult to interpret with regards to a population, as results can generally only be extended to cases that are very similar. As such, all of the treatments discussed include multiple participants above the age of 65 to support the generalization of results to the elderly population. Thus, significant treatment effects theoretically could be extended to elderly individuals if the other demographic variables match and the experimental rigor was high. It should also be noted that, although aphasia can result from any neurological injury or even progressive neurological disease, the most common cause of aphasia is stroke [9, 13, 14]. Likewise, treatment research exists almost exclusively for post-stroke aphasia. Therefore, the articles included here report results for the post-stroke population. Generalization of potential recovery to other etiologies cannot be assumed.

Fifty of the most relevant studies obtained from our search are included in this review. Primary trends included traditional behavioral speech-language therapy (with and without the use of advanced technological delivery modes), neuromodulation techniques, and adjuvant pharmacological therapies. These studies are summarized in Tables 1 (behavioral therapies) and 2 (neuromodulation therapies).

Table 1:

Studies Utilizing Behavioral Speech Language Therapy

Authors	# of Participants; Mean Age (SD) in years	Design	Intervention	# of Sessions & Duration	Results
Babbitt, et al. (2015) [24]	N = 74 54.1 (16.3)	Single group pre-post-test design	Intensive Comprehensive Aphasia Program (ICAP) in individual and group sessions	30 hours/week x 4 weeks	Examination of outcomes by participant characteristics
Breitenstein, et al. (2017) [44]	N = 156 53.2 (9.6)	RCT of treatment or waitlist (i.e., no treatment)	Individualized, comprehensive targets—hybrid delivery (1:1, group, computerized)	10+ hours/week x 3 weeks	Treatment, compared to no treatment, resulted in statistically significantly improvement on verbal communication measures.
De Luca, et al. (2018) [47]	N = 32 51.7 (14.6)	RCT of experimental or control groups	Computerized naming treatment compared to “standard” treatment	3 45-minute sessions/week x 8 weeks	All measured language outcomes improved for the experimental group, with retention at 3 months, compared to the “standard” treatment. “Standard” treatment is not well enough described for reliable comparison
DeDe, et al. (2019) [38]	N = 46 64.3 (11.9)	RCT of 2 experimental groups and control group	Conversation therapy in dyads or groups of 6–8 people	2 1-hour sessions/week x 10 weeks	Both experimental groups showed improvement over the control group, with up to 11 months retention. Dyads (groups of 2) showed greater improvement than larger treatment groups.
Dignam, et al. (2015) [28]	N = 34 58.5 (10.9)	Parallel-group, pre-post-test design	Aphasia Language and Impairment Functioning Therapy (LIFT) at 2 different intensities	Intense group: 5 3+ hour sessions/week x 3 weeks Distributed group: 3–4 1–2-hour sessions/week x 8 weeks Both groups received a total of 48 hours of treatment	Most outcomes were equal between practice schedules except for naming, which was better for the distributed group both immediately after treatment and at 1-month post.
Duncan, et al. (2016) [48]	N = 19 53.5 (11.7)	Single group pre-post-test design	Computerized imitation-based naming therapy (i.e., IMITATE)	6 30-minute sessions/week x 6 weeks	Significant improvement on standardized assessment; response was predicted by pre-treatment variability (i.e., greater variability resulted in greater treatment gains)
Duncan & Small (2017) [50]	N = 19* 54 (11.34) *Likely same cohort as Duncan et al. (2016) although age demographics are reported as slightly different	Single group pre-post-test design	Computerized imitation-based naming therapy (i.e., IMITATE)	6 30-minute sessions/week x 6 weeks	Significant improvement on narrative accuracy with treatment; positive response was predicted by number of sessions completed
Fleming, et al. (in revision) [46]	N = 35 61 (12)	Randomized, repeated measure crossover design	Self-administered computerized auditory comprehension treatment (Listen-In)	Target of 100 hours cumulative treatment over 12 weeks (mean = 85 hours)	Statistically significant gains on word and sentence comprehension measures
Gravier, et al. (2018) [34]	N = 17 59(15)	Single group pre-post-test design (multiple baseline)	Semantic Feature Analysis (SFA)	2 2-hour sessions/day x 4–5 days/week x 4 weeks	Significant improvement for treated and untreated items; response was predicted by the number of features generated (but not number of trials or total treatment time)
Hoover, et al. (2017) [25]	N = 27 56 (2.7)	Delayed treatment within-participants design	Intensive Comprehensive Aphasia Program (including individual and group therapy)	30 hours/week x 4 weeks	Significant change seen on all impairment-based measures and some functional communication and quality of life measures.
Pompon, et al. (2017) [32]	N = 26* 56 (14.5) *Same cohort as Kendall et al. (2015)	Single group pre-post-test design	Phonomotor treatment	2 1-hour sessions/day x 5 days/week x 6 weeks	Examination of predictive variables; no participant variables were found to predict response to phonomotor treatment.
Johnson, et al. (2017) [37]	N = 8 (plus 8 conversational partners) 57.63 (10.21)	Qualitative study	Conversation therapy	8 weeks duration. Session length and frequency not reported	Transcript analysis indicated seven themes reflecting potential mechanisms of change associated with conversation therapy
Kendall, et al. (2015) [31]	N = 26 56 (15)	Open-trial design of immediate and delayed treatment	Phonomotor treatment	2 1-hour sessions/day x 5 days/week x 6 weeks	Treatment resulted in generalization to naming of untrained words and phonological processes.
Kesav, et al. (2017) [43]	N = 20 52.85 (12.0)	RCT of 2 experimental groups	“Standard” treatment alone (various tasks and treatment protocols such as MIT or PACE) compared to “standard” treatment plus additional comprehensive computer-based practice	“Standard” group (non-intense): 3 1-hour sessions/week x 4 weeks Experimental group (intense): 6 1-hour sessions/week x 4 weeks (half “standard,” half computer-based)	Both groups resulted in significant improvement on standardized assessment, but more so in the control group (“standard” treatment only). Besides computerized practice, groups differed in intensity, demographic make-up and subsequent treatment tasks, so differences may not be related to the addition of computerized treatment.
Kurland, et al. (2018) [49]	N = 21 66.4 (8.4)	Single group pre-post-test design	Self-administered computer-based naming treatment	Target practice: 5–6 20-minute sessions/week x 24 weeks (actual practice time not reported)	Positive outcomes were reported, which were mediated by severity, compliance, and amount of training to utilize training platform.
Macoir, et al. (2017) [40]	N = 20 63.65 (10.1)	Single group pre-post-test design	Promoting Aphasics’ Communicative Effectiveness delivered remotely	9 sessions over 3 weeks (session duration not reported)	Communicative effectiveness was significantly improved with treatment.
Marshall, et al. (2016) [41]	N = 20 57.8 (11.6)	Quasi-RCT of treatment group and waitlist control (i.e., no treatment)	Virtual reality treatment (EVA Park) with individualized goals	5 1-hour sessions/week x 5 weeks with clinician plus 1 hour/week in group session; unlimited amount of self-practice	Functional communication and verbal fluency measures improved compared to no treatment, but self-ratings and socialization did not change. Authors could not reliably attribute changes to the treatment
Nenert, et al. (2017) [17]	N = 19* 54.6 (12.2) *subset of cohort reported by Szaflarski et al. 2015	RCT of treatment group and control	Intense Language Action Therapy (also called Constraint Induced Language Therapy)	10 4-hour sessions over 2 weeks	Examination of cortical changes following ILAT; no significant changes were observed
Nickels & Osborne (2016) [27]	N = 4 59.75 (18.66)	Single-case experimental design	Constraint Induced Language Therapy (CILT)	2 1.5-hour sessions/week x 4 weeks	Examined response to CILT when administered by a volunteer facilitator. Positive responses were seen for 3/4 participants
Palmer, et al. (2019) [42]	N = 240 64.6 (13.0)	RCT of 2 experimental groups and an attentional control	“Standard” treatment alone compared to “standard” treatment plus self-administered computerized naming treatment (StepByStep)	“Standard” treatment only (Group 1) delivered at same intensity as previous care “Standard” plus computerized (Group 2) target practice: daily 20- to 30-minute sessions x 6 months (actual average of 28 hours total)	Significantly improved naming for the addition of computerized practice compared to “standard” treatment, which was retained up to 6 months post. However, changes were limited to trained items, and did not generalize to natural contexts.
Quique, et al. (2018) [35]	N = 36 60.1 (10.5)	Meta-analysis of single-case experimental data	Semantic Feature Analysis (SFA)	Variable schedules	Improved naming of trained and untrained items, with greater response associated with higher dosages and pre-treatment language abilities.
Sandberg, et al. (2015) [30]	N = 10 59.4 (10.01)	Single-case experimental design	Naming treatment targeting abstract words	2 2-hour sessions/week, treated to criterion performance	Increased connectivity associated with trained abstract words seen in different networks than for untrained concrete words.
Stahl, et al. (2016) [20]	N = 18 51 (12)	RCT crossover design of 2 treatment groups	Intense Language Action Therapy (ILAT) and intensive naming treatment	3.5 hours/day x 6 consecutive days	ILAT was effective regardless of order administration, but the compared naming treatment was only effective when administered first (in cross-over design)
Stahl, et al., (2018) [26]	N = 30 60.1 (15.3)	RCT of 2 treatment groups	Intense Language Action Therapy (ILAT)	Intense: 4 hours/day 3x/week x 2 weeks Moderately intense: 2 hours/day 3x/week x 2 weeks	Both groups made significant improvements, with no differences between groups (i.e., intensity of treatment)
Szaflarski, et al. (2015) [18]	N = 24 54.5 (12.0)	RCT of treatment group compared to control (i.e., no treatment)	Intense Language Action Therapy (ILAT)	4 hours/day x 10 days over 2 weeks	Subjective ratings of communication were significantly different after treatment; other measures trended toward significance.
Vuksanovic, et al. (2018) [21]	N = 17 60.8 (9.4)	RCT crossover design of 2 experimental groups	Constraint Induced Language Therapy (CILT) and stimulation aphasia therapy (SAT)	Each block: 5 1-hour sessions/week x 4 weeks	Both treatments resulted in statistically significant gains, but improvements were greater for those receiving CILT first; naming improvements were greatest with CILT
Wenke, et al. (2018) [45]	N = 9 72.4 (9.4)	Small parallel-group design	Hybrid model: face-to-face, group, and computerized treatment (various targets/tasks)	Intense group: 8 hours/week x 8 weeks Non-intense group:4 hours/week x 8 weeks	Group differences were not examined; clinically meaningful changes were seen for both treatment groups.
Wilssens, et al. (2015) [22]	N = 9 66.6 (9.0)	Small parallel-group design	Constraint Induced Language Therapy (CILT) and a lexical semantic treatment	4 or 5 2–3-hour sessions/week x 2 weeks	Both groups showed positive responses to treatment, but CILT resulted in changes in production/phonology while the lexical semantic treatment resulted in changes in comprehension/semantics.
Woldag, et al. (2017) [23]	N = 60 68.2 (11.7)	RCT of 3 experimental groups	Intense Language Action Therapy (ILAT), intense “traditional” group treatment, and non-intense clinically “typical” approach	ILAT and intense traditional groups: 5 3-hour sessions/week x 2 weeks Non-intense “typical” group: 2 30-minute sessions/day x 10 sessions over two weeks plus 2 1-hour group sessions/week x 2 weeks	Significant improvements were found for all three groups with no differences between groups
Woolf, et al. (2016) [39]	N = 20 59.2 (13.1)	Quasi-RCT of 3 experimental groups and an attention control	Teletherapy (from two different sites, i.e., Groups 1 and 2) and face-to-face therapy	2 1-hour session/week x 4 weeks	Naming improved with all three experimental groups with no significant differences between face-to-face delivery and teletherapy.

Note: # = number; Tx = treatment; Exp. = experimental; RCT = randomized control trial.

Behavioral Speech-Language Therapy

For aphasia, behavioral speech and language therapy (SLT; i.e., the training/modification of specific skills/behaviors) remains the current standard of care. SLT aims to improve an individual’s ability to communicate by targeting the impairment specifically, training compensatory behaviors for lost language skills, or facilitating the use of skills in a variety of contexts.

Face-to-face SLT continues to comprise a large proportion of intervention research. Recent research has focused not only on the effectiveness of such treatments, but also on identifying variables associated with greater response to therapy (e.g., intensity, generalization, delivery mode, etc.), as well as eliminating barriers to implementation and participation (e.g., using teletherapy as a means of reducing/eliminating the burden of travel to/from the clinic).

Intense Treatment

Several studies have examined the optimal treatment intensity for acquisition and maintenance of gains. For example, is intensive practice better than distributed practice? Or, does highly intense treatment facilitate recovery better in the acute/subacute stage versus the chronic stage? Intense treatment protocols have gained popularity in recent years for two primary reasons: 1) highly intense practice is thought by some to be better for learning (i.e., acquisition and/or retention of behavior; e.g., see [15]) and/or 2) due to logistical barriers, many persons with aphasia (PWA) in the chronic stage are more likely to be able to participate when the overall time commitment is brief (i.e., weeks rather than months). Synthesis and interpretation of “intense” treatment studies is challenging, as intensity is not consistently defined or reported [29]. Thus, across most studies discussed here, it is important to note that “intense” treatment is generally described as 3–4 hours/day, 5 days a week, for 2–3 weeks.

Intensive Language-Action Therapy (ILAT; also referred to as Constraint Induced Aphasia/Language Therapy; see [16]) has been widely studied. Some studies examined the effectiveness of ILAT (e.g., [17–19]), and others have compared ILAT to other intense treatments [20–23]. In each study, ILAT was found to be effective at improving a variety of language outcomes (e.g., naming, general language measures such as comprehensive standardized assessments], communicative confidence, etc.), but not always above the comparative treatments (e.g., [17, 23]). Wilssens and colleagues found the ILAT resulted in improved production and phonology, while the compared lexical-semantic treatment improved comprehension/semantics for persons with fluent aphasia [22]. In cross-over studies where participants received both treatments, ILAT was always found to be effective, but outcomes differed based on order of administration [20, 21]. For example, participants receiving ILAT first demonstrated greater overall gains than those receiving ILAT second, suggesting that ILAT may be particularly effective in early intervention [21]. However, these comparison studies generally did not clearly report protocols for the comparative treatments, thus it is difficult to know if both treatments were targeting the same communicative functions/skills. Differential responses may have been due to the two treatments modifying different behaviors that were not equally captured by the outcome measures. Additional investigation is needed to understand if, and how, ILAT may be more effective than other behavioral intervention options, but ILAT generally results in favorable changes.

Another popular intense treatment approach is that of intensive comprehensive aphasia programs (ICAPs), where PWA will come to an aphasia clinic for a defined period of time to receive a comprehensive program of treatment including impairment-based and functional interventions across any/all modalities. Interventions are often delivered through a variety of approaches (e.g., individual/group therapy, partner training, self-practice, etc.). ICAPS have been reported to result in significant gains on overall aphasia severity ratings, impairment-based measures, and qualitative ratings of communication and participation/quality of life (QOL) [24, 25]. Positive outcomes were reported across aphasia types and severities. It is important to note that ICAPs are generally delivered at an even greater intensity than most other treatments described as “intense.” That is, the ICAPs reported by Babbitt et al. and Hoover et al. included 30 hours of treatment per week over four weeks, for a total of 120 hours [24, 25].

While many researchers and clinicians believe that high-intensity treatment is particularly effective, the effects of intense treatment are not fully understood. Recent investigations have evaluated effects of intense treatment compared to less- or non-intense treatment. Woldag et al. found no difference on standardized assessments between ILAT and non-intense “traditional” treatment, but the compared treatment was only vaguely described and tailored to individual impairments (i.e., treatment ingredients and targets were different for each individual, thus collective positive change for the group may have been confounded) [23]. Stahl compared highly intense to moderately intense ILAT (i.e., 4 compared to 2 hours/day) and likewise found both intensities resulted in equivalent gains, with no difference between the two groups [26]. Positive results with less intense ILAT have also been reported in several other studies [27, 21]. In an examination of Aphasia Language and Impairment Functioning Therapy (Aphasia LIFT) [28], two groups were compared receiving the same total amount of treatment, but either condensed into three weeks, or distributed over eight weeks. While most outcomes were equal across groups, the primary outcome (naming accuracy) showed greater improvement with the distributed schedule. Thus, while intensive treatment schedules have been shown to be effective, evidence has not demonstrated that intense treatment is more effective than non-intense treatment, partly due to considerable differences in how intensity is defined and reported across studies [29].

Generalization

Ideally, all treatment would result in generalization to performance of learned skills/behaviors beyond the specific items/contexts practiced in treatment. However, reliable generalization effects have been largely absent from current treatment evidence. Some treatment studies have focused on identifying the nature of generalized effects. For example, in naming treatments, training more complex or difficult items/tasks has been shown to generalize to less complex or difficult items [30]. Dignam found that a hybrid approach (combination of individual, group, and computerized treatment) resulted in generalized naming improvement [28]. Other studies have shown generalization to untrained stimuli by training underlying language processes such as phonological sequencing, [31] but the observed generalization was not associated with any participant variables [32]. Semantic Feature Analysis continues to be a popular and effective choice for naming treatment [33] and has been shown to generalize to untrained items [34]; see [35] for review. In Semantic Feature Analysis, greater gains have been associated with greater dosage (i.e., number of trials; [35]), baseline language performance [35], and the number of features generated [34].

Functional Approaches

Despite the demonstration of generalization to untrained items and contexts, a significant impact on functional communication is often not readily apparent. To promote more functional outcomes, some investigators have targeted individual impairment/participation goals in a group setting, such as conversation. Conversation treatment [36] has resulted in improved functional communication [37, 38] and is more effective in dyads rather than larger groups [38]. Conversation treatment was also reported to be very motivating for PWA and their partners [37].

Delivery Modes

Cost and access to aphasia intervention continues to be a challenge for PWA, particularly in subacute or chronic stages when individuals have returned home and treatment is no longer covered by insurance, or travel to an outpatient clinic is difficult. Teletherapy allows remote delivery of behavioral interventions as an alternative to the standard face-to-face delivery. Remote delivery has been demonstrated to be successful in both impairment-specific training [39] and functional communication [40]. In one study, remote and face-to-face delivery did not have significantly different effects on measured outcomes (naming in various contexts) [39]. In a novel virtual reality application allowing for client and clinician to interact in a virtual environment, improvements in functional communication and verbal fluency for trained categories was reported, but could not be reliably attributed to treatment [41]. The same study, however, did not show improved socialization or communicative confidence, suggesting that a virtual environment may not be an ideal setting for some aspects of communicative function. Additional research is needed to understand the potential role of virtual reality and other remote delivery methods.

Another approach to expanding access the use of computer-/tablet-based intervention tasks in addition to, or in place of, traditional face-to-face services. The use of software applications as an adjuvant therapy have had mixed results. While some studies have shown improved outcomes compared to the traditional treatment alone (e.g., [42]), others have found traditional delivery alone to result in better outcomes [43]. Hybrid models, combining individual, group, and computerized treatment—with individualized treatment plans and treatment ingredients—have also been shown to improve verbal/functional communication [28, 44, 45] and activity/participation [28, 45].

In the case of computerized treatment delivered [almost] exclusively through self-administration (e.g., through an app such as Listen In [46]), significant gains have been reported in naming trained items [47–49], with some generalization to untrained contexts [50], and for auditory comprehension [46]. When compared to “standard” care, reported gains with computerized treatment have exceeded those for “standard” treatment [46, 47]. Unfortunately, treatment protocols and compliance are often not well described/reported for such studies. Additional investigation is needed to determine the benefits of computerized treatment alone, and in addition to, face-to-face delivery.

Neuromodulation Techniques

Another recent trend in aphasia therapy research is investigation of the potential therapeutic role that noninvasive brain modulation techniques such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) could have for augmenting outcomes of behavioral SLT. tDCS and rTMS have already been shown to be beneficial in the treatment of aphasia. For detailed reviews of trends in non-invasive brain stimulation for aphasia, see [51, 52].

Transcranial Direct Current Stimulation

tDCS delivers a weak electrical current (usually 1 or 2 mA) via two electrodes placed on the outside of the scalp. This stimulation is believed to enhance or diminish cortical excitability depending on the application of the anodal (positive) or cathodal (negative) electrode, respectively [53]. tDCS studies identified in our search generally reported a stimulus or sham application for 20 minutes—typically, during the first 20 minutes of the concurrent SLT. The stimulation sites, quantity of sessions, and type of concurrent language tasks varied among the studies (see Table 2).

Table 2:

Studies Utilizing Neuromodulatory Therapy

Transcranial Direct Current Stimulation (tDCS)
Authors	# of Participants; Mean Age (SD) in years	Design	Intervention	# of Sessions & Duration	Sites Targeted	Results
Campana, et al. (2015) [63]	N = 20 57.1 (10.3)	Double-blind randomized crossover	A-tDCS (2mA) + conversational SLT	10 sessions per condition over 2 weeks; 20-minutes of tDCS during 1-hour SLT session	Left IFG	Significant improvement in picture description, noun naming and verb naming with active condition. Poorer response to A-tDCS observed with damage to certain left hemispheric structures (e.g., basal ganglia, insula, superior and inferior longitudinal fasciculi)
de Aguiar, et al (2015) [61]	N = 9 57 (12.7)	Double-blind randomized crossover	tDCS (1mA) + SLT focusing on verb inflection and sentence construction (ACTION)	10 sessions per condition over 2 weeks; 20 minutes of tDCS during 1-hour SLT session	Perilesional, differed by individual	Improvement in verb production (treated and untreated), but no difference between tDCS and sham (both improved)
Fiori, et al. (2019) [60]	N = 20 62 (5.9)	Double-blind randomized crossover	Cathodal High Definition tDCS at two intensities (1mA vs. 2 mA) + verb naming task	10 sessions per condition over 2 weeks; 20-minutes of tDCS during verb naming task (time for verb-naming task not reported)	Right Broca’s homologue	Significant improvement in verb naming following 2mA intensity only
Fridriksson, et al. (2018) [54]	N = 74 60 (10)	Double-blind, randomized, sham-controlled clinical trial; Futility design	A-tDCS (1mA) + computerized anomia SLT	15 sessions over 3 weeks; 20-minutes of tDCS during 45-minute SLT session	Left temporal lobe region with greatest activation during fMRI naming task	Greater improvement with A-tDCS compared to sham
Keser, et al. (2017) [78]	N = 10 56.4 (16.8)	Double-blind randomized placebo-controlled crossover; Feasibility study	Combination of pharmacological (dextroamphetamine or placebo), A-tDCS (1.5 mA), plus SLT (Melodic Intonation Therapy)	2 sessions (1 per condition); 20-minutes of tDCS plus 40 minutes of SLT combined with dextroamphetamine or placebo	Right IFG	Dextroamphetamine + tDCS group showed statistically significant changes on WAB AQ compared to placebo
Marangolo, et al. (2018) [66]	N = 12 58 (7.8)	Double-blind randomized crossover	Cerebellar C-tDCS (2mA) + SLT for verb improvement	5 consecutive daily sessions per condition: (2 active tDCS conditions and 2 sham conditions); 20 minutes of tDCS during SLT session (SLT session time not reported)	Right cerebellum	Improvement in verb generation, but little improvement in verb naming post treatment
Meinzer, et al. (2016) [56]	N = 26 60 (11.8)	Double-blind randomized sham-controlled clinical trial	A-tDCS (1mA) + intensive computer-assisted naming SLT	16 sessions over 8 days; tDCS for the first 20 minutes of two 1.5-hour intensive naming SLT sessions per day	Left primary motor cortex	Improvement in both groups, but more so in A-tDCS group; generalization to untrained items significantly better in the tDCS group post treatment and at 6 months; functional communication significantly better post treatment and at 6 months for tDCS group
Richardson, et al. (2015) [62]	N = 8 60.6 (8.9)	Single-blind randomized crossover	Conventional-tDCS (1mA) vs High Definition-tDCS + computerized anomia SLT	5 consecutive daily sessions per condition; 20 minutes of tDCS during final portion of 25-minute SLT session	Left perilesional cortex with highest activation during fMRI naming task	Naming accuracy and response times improved with both conditions. Accuracy of trained items was higher for High Definition-tDCS, but not statistically significant.
Silva, et al. (2018) [59]	N =14 52.38 (17.26)	Double-blind randomized sham-controlled clinical trial	C-tDCS (2mA)	5 consecutive daily sessions of 20 minutes of tDCS	Right hemisphere homolog to Broca’s area	Significant improvement in time for correct responses with strategy
Spielmann, et al. (2018) [58]	N = 13 53.2 (11.3)	Double-blind randomized crossover	A-tDCS (1mA) + word-finding SLT	3 sessions (1 sham, 1 tDCS over L IFG and 1 tDCS over L posterior STG) over 2–4 weeks with a 3-day minimum interval between each; 20-minutes of tDCS during 30-minute SLT session	Left IFG and Left STG	Improvement on trained items only; increase was highest in the active L-IFG condition
Spielmann, et al. (2018) [57]	N = 58 58.9 (10.0)	Double-blind randomized sham-controlled clinical trial	tDCS (1mA) + word-finding SLT	5 daily sessions/week x 1 week; tDCS during first 20 minutes of 45-minute SLT session	Left IFG	Improved naming reported for all participants; no difference between tDCS/sham on any measure.
Woodhead, et al. (2018) [55]	N = 21 53(11)	Baseline-controlled repeated-measures double-blinded crossover	A-tDCS + SLT via training app (iReadMore)	Two 4-week blocks of SLT (1 block with active tDCS and 1 with sham). Each block included 34 hours of SLT and 11 stimulation sessions	Left IFG	Increased reading accuracy for trained words with iReadMore and slight enhancement of reading accuracy for trained and untrained words with A-tDCS
Repetitive Transcranial Magnetic Stimulation (rTMS)
Authors	# of Participants; Mean Age (SD) in years	Design	Intervention	# of Sessions & Duration	Sites Targeted	Results
Griffis, et at. (2016) [68]	N = 8 54.4 (12.7)	Single group pre-post-test design	HF-rTMS (50 Hz; intermittent theta burst)	10 sessions over 2 weeks; HF-rTMS delivered for 200-second period	Residual language-responsive cortex in or near Left IFG (identified via fMRI task)	Increased left IFG activation and reduced right IFG activation post-intervention
Haghighi, et al. (2017) [72]	N = 12 61.1 (9.3)	Double-blind randomized sham-controlled clinical trial	LF-rTMS (1 Hz) + SLT	10 30-minute rTMS sessions and 10 45-minute SLT sessions over 2 weeks	Right inferior posterior frontal gyrus	Significant improvement in speech and language for all participants, but more so for rTMS compared to sham
Hara, et al. (2015) [77]	N = 50 60.3 (12.1)	Parallel group pre-post-test design	LF-rTMS (1 Hz) + intensive constraint-induced SLT	One 40-minute rTMS session + 10 60-minute intensive constraint-induced SLT sessions during 11-day hospitalization	IFG (for nonfluent aphasia) or STG (for fluent aphasia) in left or right hemisphere based on fMRI activation (opposite of language-compensatory hemisphere)	rTMS was not as effective for individuals whose language laterality had shifted to the non-lesioned hemisphere
Hara, et al. (2017) [73]	N = 8 65.6 (11.9)	Parallel group pre-post-test design	rTMS (1 Hz or 10 Hz depending on site of activation on fNIRS) + SLT	10 sessions consisting of 40-minute rTMS followed by 60 minutes of intensive SLT during 11-day hospitalization	Right Broca’s homologue	Both groups showed significant improvement of pre/post testing, no difference between the groups; imbalance of activation before treatment was resolved after treatment, per fNIRS
Harvey, et al. (2019) [71]	N = 11 55.5 (14.8)	Double-blind randomized crossover	Continuous theta burst stimulation, an inhibitory form of rTMS (5 Hz)	1 40-second session of continuous theta burst stimulation to target site and 1 40-second session to control site	right pars triangularis vs vertex (control site)	Improved naming of inconsistent, but not wrong, items for individuals with more severe baseline naming impairment found with experimental group
Hu, et al. (2018) [74]	N = 40 48.3 (10.6)	Randomized, sham controlled trial	HF-rTMS (10 Hz) vs. LF-rTMS (1 Hz) + conventional treatment, including SLT	10 total daily sessions of 10 minutes of rTMS + 30-minute daily SLT sessions (total duration in weeks, not specified)	Right hemispheric Broca’s area homologue	LF-rTMS group demonstrated greater overall improvement; positive immediate and long-term effects were observed for LF-rTMS; HF-rTMS group only demonstrated gains 2 months post-treatment
Ren, et al. (2019) [67]	N = 45 64 (12.2)	Double-blind randomized sham-controlled clinical trial	LF-rTMS (1 Hz) + SLT	15 sessions (20 minutes rTMS followed by 30-minutes of SLT per session) over 3 weeks	Right pars triangularis of the IFG or posterior STG	Significant improvement in repetition, spontaneous speech, and Aphasia Quotient in the IFG group; Significant improvement in auditory comprehension, repetition, and Aphasia Quotient in the STG group;
Rubi-Fessen, et al. (2015) [75]	N = 30 68.8 (7.3)	Randomized, blinded, sham-controlled trial	LF-rTMS (1 Hz) + SLT	10 sessions (20 minutes rTMS followed by 45 minutes of SLT per session) over 2 weeks	Right Broca’s homologue	Significant improvement in 10 measures of basic linguistic skills and in functional communication

Note: # = number; SLT = speech-language therapy, tDCS = transcranial direct current stimulation, rTMS = repetitive transcranial magnetic stimulation; A-tDCS = anodal tDCS; C-tDCS = cathodal tDCS; LF=low frequency; HF= high frequency; IFG = inferior frontal gyrus; STG = superior temporal gyrus; fMRI – functional magnetic resonance imaging; fNIRS = functional near infrared spectroscopy; mA = milliamp; min. = minute; vs = versus

Anodal-tDCS (A-tDCS) applied to the left hemisphere has been shown to positively impact language recovery in PWA in the chronic stage [54–56]. In contrast, positive effects were not found for individuals who underwent A-tDCS in the subacute stage [57]. In the latter, participants in both stimulus conditions showed improved naming with no statistical difference between tDCS and sham. Lack of a statistical difference between groups, however, may be explained by only 5 treatment sessions, gains in the experimental group that were not large enough to be identified above and beyond spontaneous recovery, or by differences between groups (e.g., 23% hemorrhagic stroke in the experimental group versus 6% in the control group).

A current aim of tDCS research is investigating optimal placement of electrodes. For example, is it better to apply positive or negative stimulation, and is such stimulation most effective when applied to perilesional or contralesional areas, to specific anatomical locations regardless of lesion location, or to areas of high activation individually identified? When comparing two configurations of A-tDCS (application over left inferior frontal gyrus [IFG] and over left posterior superior temporal gyrus [STG]) and sham stimulation, post-intervention performance was highest for the active IFG condition, suggesting that placement of stimulation can impact outcomes [58]. Additionally, application of A-tDCS over left primary motor cortex also demonstrated positive effects on language recovery [56]. Cathodal tDCS (C-tDCS; applied over the right hemisphere) has also demonstrated therapeutic effects (e.g., improved response times for noun naming [59] and improved verb naming [60]), suggestive that C-tDCS over the right hemisphere may also induce therapeutic effects.

A-tDCS and C-tDCS often utilize a reference electrode over the supraorbital region, but other modes of delivery being investigated include application of both anodal and cathodal electrodes to areas hypothesized to be pertinent to language (e.g., both activation of left hemisphere regions and inhibition of right hemisphere regions concurrently). This configuration has resulted in improvement in treated and untreated verb production; however, there was no difference between tDCS and sham conditions [61]. The stimulation site in this study was perilesional and thus slightly different for each participant, which may have contributed to the lack of a group effect. The sample size was also small, so it is difficult to draw strong conclusions.

Other important factors investigated in recent years include more precisely localized delivery of stimulation and the ideal current level. Investigators have attempted to increase precision of the stimulation site through methods such as high definition tDCS (HD-tDCS). Traditional tDCS electrodes are typically about 4×5cm in size; HD-tDCS electrodes are about 10mm in diameter allowing for a more focused delivery of current. To date, it is unclear that HD-tDCS is more effective than conventional sponge-based tDCS, but its feasibility has been shown, with effects at least comparable to conventional sponge-based tDCS [62]. Additionally, cathodal HD-tDCS applied to the right homologue of Broca’s area has resulted in improved verb naming with 2mA current delivery, but not with 1mA [60], suggesting that current delivery can also impact outcomes. However, 1 mA current is often used as it is less likely to induce scalp pain compared with 2mA [54], another important factor in the clinical setting.

Investigators are also aiming to identify which patients are the best candidates for tDCS (i.e., who benefits the most) with regard to characteristics such as lesion location, aphasia type, and impairment severity. Some lesion locations have been associated with poorer response to tDCS condition (i.e., left basal ganglia, insula, and longitudinal fasciculus [63]). In addition to identifying who will benefit most, investigators are seeking to identify the best dosage for tDCS intervention (e.g., does increasing the frequency and intensity improve outcomes?). Positive results were observed for an intensive intervention (two 1.5-hour SLT sessions per day with tDCS application during the first 20 min of each session) [56]. Effects from this dosage seemed comparatively larger than other studies, possibly related to receiving 40 minutes of tDCS per day which is twice that of most other protocols. Continued investigation along these lines of inquiry are needed.

Another novel trend in tDCS research is investigating the potential therapeutic role that tDCS may have to augment SLT when applied to the cerebellum, as this configuration targets tracts involved in language processing and can be applied without the need to consider the cerebral lesion location or identify activation sites prior to tDCS application. Cerebellar tDCS had a positive effect on language skills and improved functional connectivity in healthy younger adults [64] and in a case study of an individual with chronic post-stroke aphasia and large bilateral cortical strokes [65]. Positive effects were recently observed in a study that included multiple participants in the elderly age range [66], suggesting that this configuration could have therapeutic effects on elderly adults with chronic post-stroke aphasia. In the latter study, significant improvement was observed in verb generation but not in verb naming, indicating that cerebellar tDCS may be most effective for tasks that also require nonlinguistic strategies, as in verb generation.

Repetitive Transcranial Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) consists of the presentation of a low frequency (e.g., 1–5 Hz) or a high frequency (e.g., 10–20 Hz) magnetic pulse aimed at a targeted neurological location in order to inhibit or excite the residual function of that area [67]. In aphasia treatment applications, stimulation is delivered to the left hemisphere language networks or corresponding right hemisphere homologues. Using fMRI to examine activation and connectivity, rTMS has been shown to recruit residual language areas while reducing involvement of the right hemisphere during language tasks [68].

As with other neuromodulation techniques, various rTMS applications/ specifications (e.g., inhibitory versus excitatory stimulation, stimulation site, frequency [i.e., low versus high frequency], and dosage) have been used. While promising results of the effects of rTMS for post-stroke aphasia have been reported [67, 69–75], the ideal application parameters have not been identified. Site of application appears to have an impact on treatment outcomes in subacute post-stroke global aphasia. Ren and colleagues compared the effects of rTMS when applied to two different sites: right posterior IFG and right posterior STG [67]. Repetition and severity scores improved for both sites; however, application to posterior STG was associated with significant increases in auditory comprehension, and application to posterior IFG was associated with increases in fluency and content accuracy. Varying frequency (i.e., low versus high frequency) also affects outcomes. In a study comparing low frequency (LF-rTMS;1 Hz) to high frequency (HF-rTMS; 10 Hz), positive immediate and long-term (i.e., 2-month follow-up) effects were observed only in those who received LF-rTMS. The HF-rTMS group only demonstrated improvement at two months post-treatment, and the effects were greater overall for LF-rTMS than HF-rTMS [74]. Additional research is needed to understand the differential effects of varying application sites and frequency of rTMS.

Investigators are also seeking to identify the optimal timing of rTMS intervention after stroke and to understand who will benefit most from rTMS. Positive effects have been reported in chronic post-stroke aphasia [74]; however, LF-rTMS over the right IFG in subacute stroke has demonstrated mixed results [67, 75]. Rubi-Fessen and colleagues found no difference between active rTMS and sham stimulation in the subacute period for half of the measured outcomes [75]. Neural responsiveness to treatment may differ at different stages of recovery [76].

Mixed results across studies could also be in part due to other factors, such as differences in post-stroke language laterality (based on fMRI activation) [77] or different underlying deficits. For example, investigators found that inhibitory rTMS over the right pars triangularis facilitated phonological access during word retrieval, suggesting that impairment at this stage of production may optimally respond to this approach [71].

Pharmacological Therapies

Investigations of the potential role of medications on enhancing aphasia recovery have been scattered across the literature over the past few decades, but none have been adequately replicated. Search results yielded one current study relevant to the elderly: an investigation of effects of combination therapies (i.e., pharmacotherapy plus behavioral SLT plus neuromodulation techniques) which showed promising results [78]. Changes in language measures post-intervention were significantly higher for those who received dextroamphetamine compared to those who received a placebo in conjunction with behavioral SLT and tDCS. However, more research is needed before these treatments can be recommended. For detailed review of current trends in pharmacological interventions, see [79].

Discussion and Limitations

Since no studies identified in our search results explicitly studied the effects of aphasia therapy in the elderly population, we reviewed the most relevant studies, based on inclusion of older participants and quality of the evidence. Therefore, the results, as they pertain to the elderly, need to be examined judiciously. Most studies were relatively small, and generalizability to the population as a whole is tentative.

While results of these studies are not directly applicable to the rehabilitation potential of older adults, there is ample evidence that older adults are still capable of responding to treatment given the ample number of participants above the age of 65 across these studies. While advanced age is a factor that contributes to a reduction in neural plasticity [76], increased brain atrophy [80], and physiological changes [81], there is mixed evidence that age actually predicts post-stroke aphasia outcomes [12]. In a recent review examining age and aphasia recovery, 12 of 17 studies reported that advanced age did not influence clinical recovery patterns or outcomes [12], suggesting both that: 1) many elderly adults have comparable capacity for response to treatment as younger adults, and 2) more research is needed to understand the effects that aging has on response to aphasia therapy.

Conclusions and Future Directions

Additional research is needed to elucidate the mechanisms by which aphasia therapies enhance language performance in the elderly. Larger studies are needed to yield meaningful results. In the absence of larger studies, meta-analyses could be beneficial, but are severely limited by differences in outcome measures, delivery methods, frequency, duration, and dosages across studies. Future studies would benefit from some standardization of these areas in order to fully analyze the outcomes on a larger scale. Likewise, future study protocols on neuromodulation techniques should continue to include current strength, electrode size, electrode placement site and stimulation duration to allow investigators to compare results between studies.

Investigations specifically comparing treatment response across age groups are also needed. While training-induced neural plasticity reduces with age [76], older adults have responded positively to SLT (as indicated by investigations reported here as well as many not included in this review). It would be valuable to examine the effects of aging specifically on the outcomes of post-stroke aphasia with regard to specific interventions. The overarching goal for aphasia therapy research is to identify the most effective interventions that capitalize on principles of neural plasticity and neurorehabilitation and employ optimal intervention technique, timing, frequency and dosage to maximize language outcomes and improve quality of life for individuals of all ages.

Human and Animal Rights and Informed Consent.

This article does not contain any studies with human or animal subjects performed by any of the authors.