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Background:
Systematic Review

Safety and Efficacy of Different Therapeutic Interventions for Primary Progressive Aphasia: A Systematic Review

by
Abdulrahim Saleh Alrasheed
1,*,
Reem Ali Alshamrani
2,
Abdullah Ali Al Ameer
3,
Reham Mohammed Alkahtani
2,
Noor Mohammad AlMohish
4,
Mustafa Ahmed AlQarni
5 and
Majed Mohammad Alabdali
5
1
Department of Neurosurgery, College of Medicine, King Faisal University, AlAhsa 31982, Saudi Arabia
2
College of Medicine, Taif University, Taif 21944, Saudi Arabia
3
College of Medicine, King Faisal University, AlAhsa 31982, Saudi Arabia
4
Neurology Department, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Khobar 34445, Saudi Arabia
5
Neurology Department, College of Medicine, Imam Abdulrahman Bin Faisal University, Khobar 34445, Saudi Arabia
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(9), 3063; https://doi.org/10.3390/jcm14093063
Submission received: 28 March 2025 / Revised: 23 April 2025 / Accepted: 26 April 2025 / Published: 29 April 2025
(This article belongs to the Special Issue Current Practice and Future Perspectives of Neurological Conditions Caused by Neurodegeneration, 2nd Edition)
Browse Figure
Review Reports Versions Notes

Abstract

:
Background: Primary progressive aphasia (PPA) is a neurodegenerative disorder that worsens over time without appropriate treatment. Although referral to a speech and language pathologist is essential for diagnosing language deficits and developing effective treatment plans, there is no scientific consensus regarding the most effective treatment. Thus, our study aims to assess the efficacy and safety of various therapeutic interventions for PPA. Methods: Google Scholar, PubMed, Web of Science, and the Cochrane Library databases were systematically searched to identify articles assessing different therapeutic interventions for PPA. To ensure comprehensive coverage, the search strategy employed specific medical subject headings. The primary outcome measure was language gain; the secondary outcome assessed overall therapeutic effects. Data on study characteristics, patient demographics, PPA subtypes, therapeutic modalities, and treatment patterns were collected. Results: Fifty-seven studies with 655 patients were included. For naming and word finding, errorless learning therapy, lexical retrieval cascade (LRC), semantic feature training, smartphone-based cognitive therapy, picture-naming therapy, and repetitive transcranial magnetic stimulation (rTMS) maintained effects for up to six months. Repetitive rTMS, video-implemented script training for aphasia (VISTA), and structured oral reading therapy improved speech fluency. Sole transcranial treatments enhanced auditory verbal comprehension, whereas transcranial direct current stimulation (tDCS) combined with language or cognitive therapy improved repetition abilities. Phonological and orthographic treatments improved reading accuracy across PPA subtypes. tDCS combined with speech therapy enhanced mini-mental state examination (MMSE) scores and cognitive function. Several therapies, including smartphone-based cognitive therapy and VISTA therapy, demonstrated sustained language improvements over six months. Conclusions: Various therapeutic interventions offer potential benefits for individuals with PPA. However, due to the heterogeneity in study designs, administration methods, small sample sizes, and lack of standardized measurement methods, drawing a firm conclusion is difficult. Further studies are warranted to establish evidence-based treatment protocols.

1. Introduction

Primary progressive aphasia (PPA) is one of the clinical categories that characterizes the most common presentations of frontotemporal dementias. PPA typically manifests in the fifth or sixth decade of life and largely impairs language functions [1].
PPA symptoms vary by type but may include slowed or halting speech, decreased language use, word-finding difficulty, written or spoken sentences with abnormal word arrangement, word substitution, word mispronouncing, talking around a word, difficulty understanding some part of conversation, sudden difficulty understanding simple words, and writing, reading, and spelling problems [1]. PPA commonly emerges before the age of 65, posing unique and major psychosocial and economic challenges because people with PPA are typically in their peak working years and frequently have dependent children at home [2]. Thus, when developing a care plan, the biological, psychological, and social needs of the living individual with PPA, as well as their family members and life circumstances, should be considered [2].
Individual differences in the illness characteristics (symptoms, severity, and rate of decline) and specific social and personal circumstances contribute to patients’ experience of a progressive language or speech disorder [3]. The effects include direct linguistic, motor, and cognitive alterations that result in challenges with speaking and engaging in activities of daily living, such as working, raising a family, and sustaining social connections [4,5]. Additionally, there are financial and legal ramifications that can be more severe for those whose symptoms began before the age of 65, as these people are still in their prime earning years and may have substantial financial, professional, and parental responsibilities [6]. Psycho-emotional effects can also affect people with PPA and those close to them [7]. These effects can include fear, anxiety, and grief related to the prognosis of increasing debilitation, or feelings of humiliation, self-consciousness, and irritation over communication difficulties. Furthermore, as the illness advances, PPA care partners may experience a loss of emotional connection with their loved one and find it more difficult to communicate with them [8]. As a result, there is a significant increase in depression rates among PPA individuals and their partners [7].
Three distinct clinical variations have been discovered that vary in terms of their phenotypic presenting pattern, underlying neuropathology, and degeneration distribution/location [9]. Nonfluent/agrammatic PPA (nfvPPA) is linked to speech apraxia, labored or effortful speaking, gradual progressive impairment of language production, object naming, syntax, or word comprehension. It is also associated with left frontal lobe atrophy [10]. Word comprehension and naming impairments are commonly observed in individuals with semantic variant PPA (svPPA), which is associated with left anterior and ventral temporal lobes atrophy while maintaining speech production [11]. svPPA is diagnosed when there is anomia and impaired single-word comprehension, along with at least three of the following features: impaired object knowledge, surface dyslexia or dysgraphia, preserved repetition of words or phrases, and preserved speech production [12]. Left temporal and parietal lobe atrophy is a characteristic of logopenic variation PPA (lvPPA), which is associated with repetition difficulties, halting spontaneous speech, and difficulties with word retrieval [9,10].
Clinical features of lvPPA include impaired single-word retrieval in spontaneous speech, impaired repetition of sentences and phrases, speech (phonological) errors in spontaneous speech and naming, spared single-word comprehension and object knowledge, spared motor speech (no distortions), and the absence of frank agrammatism [13,14]. lvPPA supportive imaging findings include major left posterior peri-sylvian or parietal atrophy on MRI, as well as predominant left posterior peri-sylvian or parietal hypoperfusion or hypometabolism on SPECT or PET [13,14].
The absence of curative treatment for PPA is rooted in its pathological molecular mechanisms. Initially, brain atrophy in PPA was thought to involve broad peri-sylvian areas in the left hemisphere. However, subsequent researches linked specific PPA variants to distinct patterns of brain damage: nfvPPA is associated with atrophy in the left posterior frontal and insular regions, svPPA with the anterior temporal lobe, and lvPPA with the left temporo-parietal areas. These findings emphasize the significant influence of the involved damage location within the language network on the clinical presentation of PPA and have led to the incorporation of neuroimaging evidence into the diagnostic classification of PPA [13].
Although there is no curative treatment for PPA, an effective therapeutic approach begins with a thorough history and analysis of the patient’s speech and language components. Referral to a speech and language pathologist is critical for accurately diagnosing language impairments and developing an effective treatment strategy. Among available therapeutic interventions, speech and language therapy is the most effective one, particularly for apraxia of speech (AOS) symptoms [15]. As molecular mechanisms become increasingly understood, the need to investigate the application of neurally focused and targeted therapies, including noninvasive brain stimulation (NIBS) technologies, is warranted [11]. Recently, speech-language therapies supported by assistive devices, transcranial direct current stimulation (tDCS), and specific Alzheimer’s drugs have been explored as promising therapeutic approaches, each with a different benefit profile [1].
Due to the lack of data supporting the efficacy of symptomatic pharmaceutical therapy, many practitioners have a pessimistic outlook on treating PPA patients. Actually, for many years, speech-language pathologists around the globe have been developing specialized programs for individuals with PPA, and as a result, a variety of speech-language therapy approaches have been developed [16,17]. The most effective way to lessen the impact of speech, language, and communication deficits in PPA patients is through behavioral treatment, provided that no proven pharmaceutical treatments are used [18].
Behavioral treatment may target speech, language, and communication using listening, speaking, reading, writing, and other communicative activities and tasks [19]. Targeted behaviors include receptive language processing and comprehension, intelligible speech production, lexical retrieval (i.e., word finding), sentence or discourse production, use of communication devices or other alternative communication modalities, and strategies for conversation and functional communication [20].
Behavioral interventions may have some minor efficacy when used alone [19]. These interventions usually target a particular impairment (e.g., therapy targeted towards deficiencies in naming objects or actions) or they are participation- and activity-based therapies that try to enhance the patient’s capacity to engage in activities and tasks that they find enjoyable [21]. The use of NIBS in conjunction with behavioral language therapy might be beneficial. Effects of brain-induced stimulation frequently seem to rely on individuals’ level of effort or state [22].
Treatment for speech or language impairments in PPA is less commonly addressed and assessed, despite a strong body of evidence demonstrating the advantages of speech-language therapies for stroke-induced aphasia [23]. There are low referral rates and persistent clinical skepticism among referring and treating practitioners, particularly with regard to the communicative influence beyond the clinic [24].
Pharmacological therapies for PPA have shown limited effectiveness in improving language functions; thus, non-pharmacological therapeutic techniques are becoming increasingly popular. Despite the diversity of PPA treatments, no comprehensive study has been conducted to assess the efficacy and safety of different treatment approaches. This review aims to assess the efficacy and safety of different therapeutic interventions for PPA.

2. Methods

This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. We prospectively filed the study protocol in the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD42024503204).

2.1. Search Strategy

We conducted a systematic search of Google Scholar, PubMed, Web of Science, and the Cochrane Library databases through January 2024, with an updated search in April 2024. The search strategy employed a combination of Medical Subject Headings (MeSH terms) and Boolean operators as follows: (Primary Progressive Aphasia OR Semantic Variant OR Nonfluent Variant OR Agrammatic Variant OR svPPA OR nfvPPA OR lvPPA OR Logopenic Variant) AND (Speech Therapy OR Behavioral Therapy OR Language Therapy OR Behavioral) AND (Treatment OR Treatment Approaches OR Therapy OR Generalization OR Stimulation). Additionally, the reference lists of included articles were manually screened to identify further relevant studies.

2.2. Eligibility Criteria

This review critically examined English case-control studies, randomized controlled trials (RCTs), cohort studies, case series and single-case experimental studies investigating efficacy and safety of various therapeutic interventions for PPA in adult patients aged ≥18 years. The review encompassed all three PPA subtypes (nfvPPA, svPPA, and lvPPA). Investigated therapeutic modalities included speech-language therapy, tDCS, repetitive transcranial magnetic stimulation (rTMS), phonological and orthographic treatments, errorless learning therapy, lexical retrieval techniques (LRT), and various pharmacological interventions. Review articles, editorials, or studies assessing irrelevant outcomes were eliminated.

2.3. Outcome Measures

The investigated primary outcome measures were language gain assessed through naming and word finding for trained and untrained words, spontaneous speech or fluency, auditory verbal comprehension, repetition, apraxia of speech and reading abilities. These were assessed through various assessment tools, such as the Western Aphasia Battery or the Boston Naming Test. If unavailable, qualitative descriptions from baseline to multiple time intervals were taken into consideration.
The secondary outcome measures examined broader therapeutic effects, including cognitive function, generalization and maintenance of overall therapeutic effects, neuroplastic and functional reorganization, structural and metabolic changes, quality of life and any reported adverse events. Mini-Mental State Examination (MMSE) and qualitative descriptions were used throughout the assessment procedure.

2.4. Selection of Studies and Extraction of Data

Two reviewers independently evaluated the paper titles and abstracts, any discrepancies were addressed by a third reviewer. The gathered study characteristics included the following (first author name, publication year, country, and study design). Demographic characteristics, such as age, gender, educational level, PPA subtype, treatment duration, along with baseline tests performed prior to treatment, were documented. The implemented therapeutic modalities, along with their frequency or dosages, were recorded along with the language and cognitive outcome measures of interest.

2.5. Assessment of Quality of the Included Studies

The risk of bias was assessed according to study design using validated tools. RCTs and crossover trials were evaluated using the Cochrane Risk of Bias tool (RoB 2) [25], which examines several domains, such as randomization, deviations from intended interventions, missing outcome data, outcome measurement, and selective reporting. Non-randomized and experimental studies were assessed using the ROBINS-I tool [26], which addresses potential bias due to confounding, participant selection, intervention classification, deviations from intended interventions, missing data, outcome measurement, and selective reporting. Single-case designs and case series were appraised using the Joanna Briggs Institute (JBI) checklist [27], evaluating aspects such as patient selection, clarity of intervention, outcome measurement, and adequacy of follow-up.

2.6. Statistical Analysis

A qualitative synthesis was conducted to evaluate the efficacy and safety of various therapeutic interventions for PPA. Data were extracted from eligible studies and systematically categorized based on intervention type, cognitive and language outcomes, generalization effects, neuroplastic changes, and adverse events. Quantitative outcomes, such as MMSE scores and neuroimaging findings, were summarized descriptively. Where applicable, we analyzed trends in the treatment efficacy, maintenance of gains, and structural or metabolic brain changes to identify patterns across interventions. The findings were synthesized to provide a comprehensive overview of the impact and sustainability of therapeutic approaches for PPA.

3. Results

3.1. Search Results

A total of 194 records were identified through electronic databases search process. 109 records were screened after duplicates removal, of which 38 articles were eliminated as they were assessing post-stroke aphasia. The full texts of the remaining 71 studies were assessed for eligibility, leading to the exclusion of 14 studies due to inappropriate study design. Ultimately, 57 studies involving 655 patients met the inclusion criteria and were included in the qualitative analysis (Figure 1).

3.2. Study Characteristics

A total of 57 studies, including 655 patients, were included in this systematic review [17,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83] encompassing a diverse range of study designs, including RCTs [20,29,32,33,35,37,38,44,55,60,61,74,75,82], experimental studies (prospective studies and case series that implemented pre/post intervention outcome assessment) [17,29,31,34,36,41,42,43,45,48,54,62,69,70,81,83], and single-case experimental studies [30,39,40,46,49,50,51,52,53,57,58,59,63,64,65,66,67,68,71,72,73,76,77,78,79,80]. The studies evaluated different therapeutic approaches, including speech-language therapy [28,29,38,40,43,55,63,65,72,73,75], tDCS [28,32,38,44,45,55,57,60,61,74,75,80,82], rTMS [35,51], phonological and orthographic treatments [31,41,42,50,52,77], errorless learning therapy [36,49,66,70], LRT [36,39,43,48,51,63], and pharmacological interventions, such as zolpidem [81].
The duration of interventions varied markedly across studies, ranging from 1 week [78] to 72 weeks [67]. Sample sizes also demonstrated substantial variability, spanning from single-case experimental studies [30,39,40,46,50,51,53,56,57,63,65,66,68,73,78,83] to larger cohorts of up to 49 participants [29]. The mean age of participants across individual studies ranged from 48 years [65] to 80 years [59], with reported standard deviations reflecting within-study variability. The overall pooled mean age was 63.62 years, with a standard deviation of 10.91, as presented in (Table 1).

3.3. Risk of Bias Assessment

The majority of the included RCTs exhibited a low to moderate risk of bias, with concerns primarily related to blinding of participants and outcome assessors (Table 2). Most of the non-randomized studies demonstrated a moderate to high risk of bias, particularly in confounding and selection bias due to the nature of their designs (Table 3).
Most single-case experimental design studies and case series showed a moderate to high risk of bias, especially concerning patient selection, intervention clarity, and outcome measurement. While these studies provide valuable insights into specific cases, the inherent limitations in generalizability and potential for reporting bias should be considered when interpreting findings (Table 4).

3.4. Overall Treatment Effects

Treatment effects were reported as overall effects in Table 5, with detailed documentation of each treatment modality and its therapeutic potential presented in (Supplementary Material).

3.5. Treatment Gain

3.5.1. Naming and Word Finding for Trained and Untrained Words

Various therapeutic interventions have demonstrated effectiveness in improving naming and word-finding abilities in individuals with PPA. While tDCS combined with language therapy, speech-language therapy (SLT) and phonological-orthographic treatments consistently enhance naming accuracy and lexical retrieval, interventions like errorless learning therapy, lexical retrieval cascade (LRC), semantic feature training, smartphone-based cognitive and picture-naming therapy, and rTMS showed varying degrees of generalization and maintenance over time, with some extending benefits up to six months post-treatment [28,30,33,39,42,43,44,46,50,54,58,62,63,66,68,70,75,76,77,82,83].

3.5.2. Spontaneous Speech or Fluency

Various interventions have shown promise in improving spontaneous speech and fluency in individuals with PPA. Smartphone-based cognitive therapies, picture naming, and tDCS combined with language therapy enhanced phonemic fluency and speech rate. Other approaches, like rTMS, video-implemented script training for aphasia (VISTA) therapy, and structured oral reading therapy contributed to gains in grammatical accuracy, mean length of utterance (MLU), and reduced speech errors, though semantic fluency improvements were less consistent across the studies [30,33,34,35,39,48,49,51,54,56,57,63,64].

3.5.3. Auditory Verbal Comprehension

The effectiveness of various treatment modalities in improving auditory–verbal comprehension in individuals with PPA has been extensively studied. Transcranial therapies, such as tDCS combined with language therapy, SLT, phonological and orthographic treatments, LRC, smartphone-based cognitive and picture-naming therapy, rapid retraining of items with a cognitive-oriented enhancements approach, and the VISTA, have demonstrated significant gains, with some studies reporting generalization to untrained stimuli and sustained improvements for up to six months post-treatment [28,30,33,34,36,37,39,41,42,43,44,45,46,48,50,54,58,63,66,68,70,75,77,82,83].

3.5.4. Repetition

The studies examining interventions for repetition abilities in individuals with PPA highlight a range of treatment modalities with varying degrees of effectiveness. tDCS combined with language therapy and/or cognitive therapy demonstrated significant post-treatment gains [1,14,16,20,33,40,47,52]. Although SLT and errorless learning therapy have been effective, other approaches, such as rTMS, phonological and orthographic, cognitive and picture-naming therapy, LRC, and VISTA therapy, showed limited or no significant improvements in repetition abilities [29,30,34,35,42,43,49,50,52,55,66,73,76,79].

3.5.5. AOS

The treatment of AOS in individuals with PPA has been explored through various therapeutic modalities, with several interventions showing promising results. VISTA therapy and lexical facilitation training (LeFT) combined with tDCS demonstrated notable speech accuracy improvements [34,39,45,57]. Additionally, tDCS, high-definition tDCS (HD-tDCS), structured oral reading therapy, and rTMS have contributed to enhanced speech fluency, word retrieval, and reading efficiency, though outcomes vary depending on the therapy approach [35,52,53,55,56,63].

3.5.6. Reading Abilities

Phonological and orthographic treatments have been effective in improving reading accuracy across different PPA subtypes, particularly in maintaining written naming accuracy for patients with lvPPA [41,42,63]. While errorless learning therapy has shown benefits across multiple PPA variants, rTMS has produced mixed results, with some studies reporting improvements in reading efficiency and others indicating declines in performance post-treatment [35,36,62,66,67].

3.5.7. Cognitive Function

The effectiveness of various therapeutic interventions for PPA in improving language and cognitive function was assessed across studies. tDCS combined with speech/language therapy enhanced MMSE scores and cognitive performance, while SLT, LRC, and phonological and orthographic treatments showed variable and limited effects [28,29,38,42,43,45,48,50,52,63,68,76,77,80]. Smartphone-based cognitive therapy produced the most significant cognitive gains, highlighting its potential for enhancing language and memory functions [30].

3.5.8. Maintenance of Therapeutic Effects

The long-term retention of treatment benefits varied across interventions, with tDCS, errorless learning therapy, smartphone-based cognitive therapy, SLT and phonological therapy demonstrating sustained effects for several months [28,29,36,37,38,41,42,48,63,66,68,70,75,80]. Smartphone-based cognitive therapy and VISTA maintained language improvements over six-month follow-ups, supporting their role in prolonged therapeutic impact [32,36,41,47]. Repetitive rehabilitation for impaired phonological processing (RRIPP) combined with cognitive and executive naming (COEN) therapy demonstrated some maintenance of trained item improvements, though generalization effects were limited [46,78].

3.5.9. Neuroplastic, Functional Reorganization, and Metabolic Changes

Therapeutic interventions induced neuroplastic changes, with tDCS promoting cortical activation in peri-lesional and contralateral regions, while phonological and orthographic treatments and SLT approaches enhanced structural connectivity in language-related areas [28,29,42,48,75,77].
Brain imaging studies revealed structural and metabolic changes following interventions. tDCS combined with SLT was associated with increased gray matter density in the left inferior frontal cortex [8,82]. Errorless learning therapy resulted in improved metabolic activity in the left temporal lobe, while LRC therapy enhanced functional connectivity in temporal-parietal regions [62,76]. Additionally, VISTA showed improved glucose metabolism in key language-related areas, suggesting metabolic support for language gains [45].

3.5.10. Quality of Life

Participants experienced improvements in communication abilities, social engagement, and functional daily interaction following tDCS, VISTA therapy, and smartphone-based cognitive therapy [28,30,39,45,48].

3.5.11. Adverse Events

Adverse events were generally mild and infrequent. Some participants undergoing tDCS reported transient headaches and scalp discomfort [80,82]. SLT and phonological/orthographic treatment interventions did not result in notable adverse effects [29,76]. Errorless learning therapy and LRC therapy had no significant adverse events were reported [49,76]. Overall, interventions were well tolerated, with no reports of serious adverse effects.

4. Discussion

4.1. Summary of Findings

Our systematic review encompassed 57 studies involving a total of 655 individuals diagnosed with PPA. The included studies evaluated a wide range of therapeutic interventions, ranging from phonological and orthographic treatments, repetition-based strategies, errorless learning, and lexical retrieval programs to augmentative and socially interactive communication therapies.
Our findings demonstrate consistent improvements across major language domains. Notably, naming and word finding showed lasting improvements when tDCS was combined with structured language therapies, including lexical retrieval and errorless learning strategies [28,36]. Speech fluency was significantly enhanced with phonemic-based interventions, such as VISTA and structured oral reading, particularly in non-fluent PPA variants, while comprehension and repetition showed marked benefits when semantic cueing or ICAT-based tDCS protocols were implemented [28,34]. These improvements extended in some cases to untrained stimuli, indicating generalization effects.
Long-term maintenance of therapeutic outcomes was observed in multiple studies, with retention of language gains lasting up to 15 months following intervention. Furthermore, group-based therapy formats provided additional benefits, including improved psychosocial well-being, communication confidence, and patient engagement [42]. Overall, these findings reinforce the clinical relevance of personalized, multimodal treatment approaches for managing progressive language impairments in PPA.
A detailed interpretation of therapeutic outcomes reveals domain-specific patterns across PPA interventions. Fluency outcomes were notably enhanced through phonemic-focused strategies, such as VISTA and structured oral reading, with observable gains in speech rate and grammatical construction [34]. Comprehension significantly improved when tDCS was paired with semantic or orthographic strategies, and in some cases, the improvements generalized to untrained material, suggesting deeper neurocognitive adaptation. Repetition responded best to tDCS combined with ICAT, while other approaches yielded variable results depending on baseline severity. In treating AOS, the combination of oral reading, LeFT, and neuromodulation produced meaningful improvements in fluency and articulation, particularly in complex phonemic contexts [34].
Reading interventions, especially phonological and orthographic treatments, proved highly effective in logopenic PPA patients. rTMS-based therapies showed more inconsistent results in this domain. Wider cognitive benefits were most evident with smartphone-assisted therapies, which enhanced attention and memory, whereas traditional SLT alone showed limited cognitive spillover. These behavioral improvements were supported by neuroimaging findings, which revealed increased gray matter volume and functional connectivity in language-related cortical regions. Furthermore, group-based interventions demonstrated additional benefits in psychosocial well-being and communication efficacy, reinforcing the importance of socially interactive and augmentative strategies [84]. Finally, personalized, technology-supported interventions consistently yielded better adherence and outcomes, emphasizing the need for individualized care models in PPA rehabilitation.
Overall, the observed consistent improvement in most of the analyzed studies supports the efficacy of the implemented intervention, highlighting their potential role in improving communication and quality of life in patients with PPA.

4.2. Comparison with Previous Systematic Reviews

The current systematic review findings align with multiple findings from the provided literature, reinforcing the effectiveness of targeted interventions for different PPA subtypes. Cotelli et al. [85] demonstrated that language training, particularly when combined with tDCS, significantly enhances oral and written naming abilities in PPA patients, with sustained improvements over time. This supports the current findings on phonological and orthographic treatments improving word retrieval and reading accuracy, as well as repetition-based therapies aiding fluency and spontaneous speech.
Similarly, Nissim et al. [86] confirmed that tDCS and TMS contribute to language enhancement, particularly naming ability. This aligns with the results of the current review indicating that repetition-based therapies significantly improve verbal output in logopenic PPA. However, their emphasis on the need for further research to establish optimal treatment protocols mirrors the variation in reaction rates noted in your review, highlighting the necessity for individualized therapy plans.
Lomi et al. [87] provided a more cautious perspective, indicating that while NIBS techniques had slightly better outcomes when combined with speech-language therapy, overall effects were not statistically significant. This suggests that while NIBS may be beneficial, its role as a standalone intervention is limited, reinforcing the importance of comprehensive treatment strategies, as the current review advocates.
Watanabe et al. [84] explored speech and language therapy groups for PPA, suggesting that group interventions improve communication function and psychosocial well-being. While the current review primarily focused on individual interventions, the inclusion of augmentative communication techniques aligns with their findings, suggesting that structured and socially engaging interventions may offer further benefits.
Overall, our findings resonate with the broader literature, underscoring the necessity of subtype-specific and individualized treatment approaches while reinforcing the efficacy of phonological, orthographic, repetition-based, and comprehension-focused therapies in preserving linguistic function in PPA patients. In comparison to the current literature, to the best of our knowledge, our study provides the first and most comprehensive study assessing different therapeutic interventions for patients with PPA.

4.3. Clinical Implications of PPA

PPA is a neurodegenerative disorder characterized by the gradual impairment of language abilities while other cognitive functions remain relatively preserved in the early stages [88]. PPA is classified into three main subtypes: nonfluent/agrammatic, semantic, and logopenic, each presenting distinct linguistic deficits [12,13]. nfvPPA is marked by effortful speech, agrammatism, and impaired syntactic processing, often progressing to AOS [89]. svPPA is associated with profound word comprehension deficits and impaired object recognition, whereas lvPPA is characterized by impaired word retrieval and sentence repetition due to phonological processing deficits [62]. Epidemiologically, PPA is a relatively rare condition, with an estimated incidence of three to four per 100,000 individuals, typically manifesting between the ages of 50 and 70 [90].
PPA has a profound impact on patients’ quality of life, affecting communication, social interactions, and overall cognitive function [91]. The progressive nature of the disorder leads to increasing dependence on caregivers, with language deficits impairing daily activities, such as reading, writing, and verbal expression [91]. Diagnosis is primarily clinical, based on specific core features, including progressive language impairment for at least two years, while neuroimaging aids in distinguishing PPA from other neurodegenerative conditions [92]. Notably, mixed or unclassified PPA cases present diagnostic challenges, as some patients exhibit overlapping features of multiple subtypes [12,93].

4.4. Pathophysiology and Treatment Considerations

The pathophysiology of PPA is rooted in progressive neurodegeneration, primarily affecting the language-dominant left hemisphere [94]. At a molecular level, abnormal protein aggregations, such as tau (associated with FTLD-tau) and TDP-43, linked to FTLD-TDP, contribute to neuronal dysfunction and loss [95]. Neuroimaging studies consistently reveal asymmetric atrophy, hypoperfusion, and hypometabolism in language-related brain regions, particularly in the left peri-sylvian cortex, anterior temporal lobe, and inferior parietal lobe, depending on the subtype [96,97]. Structural MRI often demonstrates cortical thinning, while PET and SPECT scans highlight metabolic deficits correlating with clinical symptoms [97].
Neuroimaging findings and gross structural brain changes in PPA vary by subtype, reflecting the distinct neurodegenerative patterns underlying each variant. In nfvPPA, structural MRI typically reveals atrophy in the left posterior fronto-insular regions, including the inferior frontal gyrus and premotor cortex, accompanied by cortical thinning and ventricular enlargement [98]. PET and SPECT imaging demonstrate hypometabolism and hypoperfusion in these regions, correlating with deficits in speech production and syntactic processing [96,97]. In svPPA, imaging studies consistently show marked atrophy and hypometabolism in the anterior temporal lobes, particularly on the left, which aligns with impairments in semantic knowledge and object recognition [97]. The degree of atrophy in svPPA is often associated with the severity of word-finding difficulties and loss of conceptual knowledge.
For lvPPA, neuroimaging findings indicate significant atrophy in the left temporoparietal junction, including the superior temporal gyrus and inferior parietal lobe [97]. PET and SPECT imaging further reveal hypoperfusion and hypometabolism in the temporoparietal cortex, which parallels the progression of linguistic impairments over time [99]. Unlike nfvPPA and svPPA, lvPPA is strongly linked to underlying Alzheimer’s disease pathology, as evidenced by amyloid and tau deposition on PET imaging.
Each PPA subtype exhibits distinct neuropathological patterns influencing its clinical presentation and response to interventions. The nfvPPA is most commonly associated with tau pathology, leading to atrophy in the left posterior frontal lobe, particularly the inferior frontal gyrus and insula [13,89]. In contrast, svPPA is predominantly linked to TDP-43 pathology, causing significant anterior temporal lobe atrophy and impairing semantic memory [99]. lvPPA is often associated with Alzheimer’s disease pathology (amyloid-beta and tau), leading to dysfunction in the left posterior superior temporal and inferior parietal cortices [100,101]. These pathophysiological differences influence treatment approaches; for example, interventions targeting phonological processing are more effective in lvPPA, whereas svPPA requires strategies focusing on conceptual knowledge and word retrieval [62].
Neuroplasticity plays a critical role in PPA, as the progressive degeneration of language-related regions necessitates compensatory mechanisms in preserved cortical and subcortical networks. Functional imaging studies suggest that right hemisphere homologs of affected left hemisphere structures may contribute to language reorganization [102]. However, the extent to which these compensatory changes facilitate functional recovery varies among patients. Theories of progressive aphasia adaptation propose that early intervention can enhance residual neural pathways, slowing functional decline [12,88].
The management of PPA remains challenging due to the lack of a universally accepted treatment consensus. Unlike other neurodegenerative conditions, PPA presents with diverse linguistic impairments based on its subtypes, making it difficult to establish standardized guidelines [102]. Current treatment approaches primarily focus on symptomatic management, utilizing speech-language therapy, cognitive training, and, in some cases, pharmacological interventions targeting underlying neuropathology [62].
Despite the lack of a universal consensus, several well-recognized guidelines, including those from the American Academy of Neurology (AAN) and the International Classification of Frontotemporal Dementias (FTD), provide diagnostic and treatment recommendations for PPA [13]. Diagnostic criteria emphasize progressive language decline lasting at least two years, with neuroimaging confirming focal atrophy patterns consistent with each subtype [97]. The Gorno-Tempini et al. [12] criteria remain the most widely accepted classification system, distinguishing nfvPPA, svPPA, and lvPPA based on linguistic deficits and neuroimaging findings. However, difficulties in establishing treatment guidelines arise due to the heterogeneity of PPA, variability in disease progression, and the lack of disease-modifying therapies.
Treatment guidelines focus on structured language interventions tailored to the specific linguistic deficits of each subtype. For nfvPPA, speech therapy targets motor speech production and grammatical structures, utilizing motor speech drills and syntactic exercises [12]. In svPPA, therapy emphasizes semantic feature analysis and compensatory communication strategies. Meanwhile, lvPPA interventions primarily address phonological working memory deficits through repetition-based and lexical retrieval exercises [91]. Pharmacological treatments remain an area of debate, with cholinesterase inhibitors and memantine showing potential benefits in lvPPA, which shares an Alzheimer’s disease-related pathology, while frontotemporal forms of PPA lack effective pharmacological options [103]. The European Federation of Neurological Societies (EFNS) highlights the importance of individualized, multidisciplinary care incorporating behavioral, cognitive, and technological interventions [104].
Early and ongoing SLT plays a crucial role in managing language deterioration in PPA. Early intervention allows patients to develop compensatory strategies that help maintain communication abilities for as long as possible. Traditional SLT approaches focus on structured exercises targeting phonological, orthographic, and semantic deficits specific to each PPA subtype [105]. In addition to conventional speech therapy, augmentative and alternative communication (AAC) methods, such as communication boards, text-to-speech applications, and symbol-based AAC devices, provide essential support when verbal communication declines [106].
Psychosocial support is equally critical, as PPA significantly impacts both patients and their caregivers [94]. Mental health screening should be integrated into clinical care to identify symptoms of anxiety, depression, and caregiver burden [106]. Cognitive and behavioral therapies offer coping mechanisms that help patients manage frustration, social withdrawal, and emotional distress [107]. Psychosocial interventions, including counseling, caregiver training, and support groups, can provide emotional support and practical guidance on navigating the challenges of PPA [106]. Educating families about the disorder’s progression and offering structured social support networks can help mitigate relationship strain, ensuring that patients maintain a sense of belonging and emotional well-being [107].
As PPA progresses, long-term care and palliative support become essential considerations. End-of-life care planning, including legal and financial decision-making, should be discussed early, while the patient can still express their preferences [107]. The involvement of palliative and hospice care teams ensures that both physical symptoms and emotional distress are managed effectively, enhancing the patient’s comfort and dignity [102]. Ethical considerations, particularly in decision-making capacity and patient autonomy, pose challenges as cognitive decline progresses. Healthcare providers must advocate for patient-centered care, ensuring that individuals with PPA retain agency over their treatment decisions for as long as possible while supporting families in making informed, compassionate choices when the patient’s ability to communicate diminishes [94].

4.5. Study Strengths and Limitations

Our systematic review provides the most up-to-date and comprehensive synthesis of therapeutic modalities for PPA by integrating more than 50 studies, which is an exceptional volume for such a rare neurodegenerative disorder. Although the inclusion of single-case designs confers reduced internal validity and bias susceptibility, their inclusion is warranted for PPA being a rare neurodegenerative disorder with a limited number of well-conducted RCTs. Omitting lower-level evidence would leave sizeable knowledge gaps and risk of publication bias. Nevertheless, considerable heterogeneity in sample sizes, study designs, intervention protocols, and outcome metrics limits direct comparison across studies and precludes firm subtype-specific recommendations. Standardizing these elements in future research will be essential for generating more uniform and clinically actionable conclusions.

4.6. Future Directions

Given the high heterogeneity observed in this review, future research should focus on standardizing intervention protocols and outcome measures to improve comparability between studies. Conducting large-scale, multicenter RCTs with well-defined diagnostic criteria will be essential to establish evidence-based treatment guidelines.

5. Conclusions

Our review demonstrates that several therapeutic interventions are effective in improving language function in individuals with PPA. Speech-language therapy, particularly when combined tDCS, has been associated with consistent gains in naming ability, speech fluency, and lexical retrieval. Group-based therapy approaches have also shown beneficial effects in enhancing both communication skills and social interaction. Conversely, NIBS, when used alone, has shown limited effectiveness, and pharmacological interventions have not yielded substantial improvements in language function. Importantly, across all included studies, the reviewed interventions were reported to be safe and well-tolerated, with no significant adverse effects. These findings support the adoption of personalized, multimodal therapeutic strategies that integrate behavioral and neuro-modulatory interventions to optimize communication outcomes in individuals with PPA.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm14093063/s1. A detailed documentation of each treatment modality and its therapeutic potential.

Author Contributions

A.S.A. had full access to all the data in the study and takes responsibility for its integrity and the accuracy of the data analysis. All authors contributed to data abstraction and drafting the first version of the manuscript. A.S.A. and M.M.A. supervised the study. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

All data generated or analyzed during this study are included in this published article [and its Supplementary Information Files].

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Tippett, D.C.; Hillis, A.E.; Tsapkini, K. Treatment of primary progressive aphasia. Curr. Treat. Options Neurol. 2015, 17, 34. [Google Scholar] [CrossRef]
  2. Nickels, L.; Croot, K. Understanding and living with primary progressive aphasia: Current progress and challenges for the future. Aphasiology 2014, 28, 885–899. [Google Scholar] [CrossRef]
  3. Hardy, C.J.D.; Taylor-Rubin, C.; Taylor, B.; Harding, E.; Gonzalez, A.S.; Jiang, J.; Thompson, L.; Kingma, R.; Chokesuwattanaskul, A.; Walker, F.; et al. Symptom-led staging for semantic and non-fluent/agrammatic variants of primary progressive aphasia. Alzheimer’s Dement. 2024, 20, 195–210. [Google Scholar] [CrossRef]
  4. Moeller, S.; Sridhar, J.; Martersteck, A.; Coventry, C.; Kuang, A.; Zhang, H.; Weintraub, S.; Mesulam, M.; Rogalski, E. Functional decline in the aphasic variant of Alzheimer’s disease. Alzheimer’s Dement. 2021, 17, 1641–1648. [Google Scholar] [CrossRef]
  5. Morhardt, D.J.; O’Hara, M.C.; Zachrich, K.; Wieneke, C.; Rogalski, E.J. Development of a psycho-educational support program for individuals with primary progressive aphasia and their care-partners. Dementia 2019, 18, 1310–1327. [Google Scholar] [CrossRef] [PubMed]
  6. Karageorgiou, E.; Miller, B.L. Frontotemporal lobar degeneration: A clinical approach. Semin. Neurol. 2014, 34, 189–201. [Google Scholar] [CrossRef] [PubMed]
  7. Ruggero, L.; Nickels, L.; Croot, K. Quality of life in primary progressive aphasia: What do we know and what can we do next? Aphasiology 2019, 33, 498–519. [Google Scholar] [CrossRef]
  8. Davies, K.; Howe, T. Experiences of living with primary progressive aphasia: A scoping review of qualitative studies. Am. J. Alzheimer’s Dis. Other Dement. 2020, 35, 1–10. [Google Scholar] [CrossRef]
  9. Montembeault, M.; Brambati, S.M.; Gorno-Tempini, M.L.; Migliaccio, R. Clinical, anatomical, and pathological features in the three variants of primary progressive aphasia: A review. Front. Neurol. 2018, 9, 692. [Google Scholar] [CrossRef]
  10. Moya, A.; Isaacson, R.; Sun, D. 141st Annual Meeting of the American Neurological Association. Ann. Neurol. 2016, 80, S1. [Google Scholar] [CrossRef]
  11. Thompson, C.K.; Mack, J.E. Grammatical impairments in PPA. Aphasiology 2014, 28, 1018–1037. [Google Scholar] [CrossRef] [PubMed]
  12. Tippett, D.C. Classification of primary progressive aphasia: Challenges and complexities. F1000Research 2020, 9, 64. [Google Scholar] [CrossRef]
  13. Gorno-Tempini, M.L.; Hillis, A.E.; Weintraub, S.; Kertesz, A.; Mendez, M.; Cappa, S.F.; Ogar, J.M.; Rohrer, J.D.; Black, S.; Boeve, B.F.; et al. Classification of primary progressive aphasia and its variants. Neurology 2011, 76, 1006–1014. [Google Scholar] [CrossRef] [PubMed]
  14. UCSF Weill Institute for Neurosciences. A Healthcare Provider’s Guide to the Logopenic Variant of Primary Progressive Aphasia (lvPPA). 2024. Available online: https://memory.ucsf.edu/sites/memory.ucsf.edu/files/wysiwyg/UCSF_lvPPA_Providers_7-13-17.pdf (accessed on 12 March 2025).
  15. Cadório, I.; Lousada, M.; Martins, P.; Figueiredo, D. Generalization and maintenance of treatment gains in primary progressive aphasia (PPA): A systematic review. Int. J. Lang. Commun. Disord. 2017, 52, 543–560. [Google Scholar] [CrossRef]
  16. Fried-Oken, M.; Rowland, C.; Gibbons, C. Providing augmentative and alternative communication treatment to persons with progressive nonfluent aphasia. Perspect. Neurophysiol. Neurogenic Speech Lang. Disord. 2010, 20, 21–25. [Google Scholar] [CrossRef]
  17. Rogalski, E.J.; Saxon, M.; McKenna, H.; Wieneke, C.; Rademaker, A.; Corden, M.E.; Borio, K.; Mesulam, M.; Khayum, B. Communication Bridge: A pilot feasibility study of internet-based speech-language therapy for individuals with progressive aphasia. Alzheimer’s Dement. Transl. Res. Clin. Interv. 2016, 2, 213–221. [Google Scholar] [CrossRef] [PubMed]
  18. Simon, P.; Rosenbaum, S. Speech and Language Disorders in Children: Implications for the Social Security Administration’s Supplemental Security Income Program; National Academies Press: Washington, DC, USA, 2016. [Google Scholar] [CrossRef]
  19. Hodges, J.R.; Piguet, O. Progress and challenges in frontotemporal dementia research: A 20-year review. J. Alzheimer’s Dis. 2018, 62, 1467–1480. [Google Scholar] [CrossRef]
  20. Rogalski, E.J.; Khayum, B. A life participation approach to primary progressive aphasia intervention. Semin. Speech Lang. 2018, 39, 284–296. [Google Scholar] [CrossRef]
  21. Croot, K.; Nickels, L.; Laurence, F.; Manning, M. Impairment- and activity/participation-directed interventions in progressive language impairment: Clinical and theoretical issues. Aphasiology 2009, 23, 125–160. [Google Scholar] [CrossRef]
  22. Gill, J.; Shah-Basak, P.P.; Hamilton, R. It’s the thought that counts: Examining the task-dependent effects of transcranial direct current stimulation on executive function. Brain Stimul. 2015, 8, 253–259. [Google Scholar] [CrossRef]
  23. Munasinghe, T.U.; Ariyasena, A.D.K.; Siriwardhana, D.D. Speech therapy interventions for acquired apraxia of speech: An updated systematic review. Am. J. Speech-Lang. Pathol. 2023, 32, 1336–1359. [Google Scholar] [CrossRef] [PubMed]
  24. Volkmer, A.; Spector, A.; Warren, J.D.; Beeke, S. Speech and language therapy for primary progressive aphasia: Referral patterns and barriers to service provision across the UK. Dementia 2020, 19, 1349–1363. [Google Scholar] [CrossRef] [PubMed]
  25. Sterne, J.A.C.; Savović, J.; Page, M.J.; Elbers, R.G.; Blencowe, N.S.; Boutron, I.; Cates, C.J.; Cheng, H.Y.; Corbett, M.S.; Eldridge, S.M.; et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ 2019, 366, l4898. [Google Scholar] [CrossRef]
  26. Sterne, J.A.C.; Hernán, M.A.; Reeves, B.C.; Savović, J.; Berkman, N.D.; Viswanathan, M.; Henry, D.; Altman, D.G.; Ansari, M.T.; Boutron, I.; et al. ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016, 355, i4919. [Google Scholar] [CrossRef] [PubMed]
  27. JBI. JBI Manual for Evidence Synthesis; JBI: North Adelaide, Australia, 2024. [Google Scholar] [CrossRef]
  28. Tsapkini, K.; Webster, K.T.; Ficek, B.N.; Desmond, J.E.; Onyike, C.U.; Rapp, B.; Frangakis, C.E.; Hillis, A.E. Electrical brain stimulation in different variants of primary progressive aphasia: A randomized clinical trial. Alzheimer’s Dement. Transl. Res. Clin. Interv. 2018, 4, 461–472. [Google Scholar] [CrossRef]
  29. Rogalski, E.; Roberts, A.; Salley, E.; Saxon, M.; Fought, A.; Esparza, M.; Blaze, E.; Coventry, C.; Mesulam, M.-M.; Weintraub, S.; et al. Communication partner engagement: A relevant factor for functional outcomes in speech-language therapy for aphasic dementia. J. Gerontol. Psychol. Sci. 2021, 77, 1017–1025. [Google Scholar] [CrossRef]
  30. Joubert, S.; Maquestiaux, F.; Enriquez-Rosas, A.; Villalpando, J.M.; Brodeur, C.; Bier, N. Smartphone use as an efficient tool to improve anomia in primary progressive aphasia. Neuropsychol. Rehabil. 2024, 34, 362–387. [Google Scholar] [CrossRef]
  31. Meyer, A.M.; Snider, S.F.; Tippett, D.C.; Saloma, R.; Turkeltaub, P.E.; Hillis, A.E.; Friedman, R.B. Baseline conceptual-semantic impairment predicts longitudinal treatment effects for anomia in primary progressive aphasia and Alzheimer’s disease. Aphasiology 2024, 38, 205–236. [Google Scholar] [CrossRef]
  32. de Aguiar, V.; Zhao, Y.; Ficek, B.N.; Webster, K.; Rofes, A.; Wendt, H.; Frangakis, C.; Caffo, B.; Hillis, A.E.; Rapp, B.; et al. Cognitive and language performance predicts effects of spelling intervention and tDCS in primary progressive aphasia. Cortex 2020, 124, 66–84. [Google Scholar] [CrossRef] [PubMed]
  33. Nissim, N.R.; Harvey, D.Y.; Haslam, C.; Friedman, L.; Bharne, P.; Litz, G.; Phillips, J.S.; Cousins, K.A.Q.; Xie, S.X.; Grossman, M.; et al. Through thick and thin: Baseline cortical volume and thickness predict performance and response to transcranial direct current stimulation in primary progressive aphasia. Front. Hum. Neurosci. 2022, 16, 907425. [Google Scholar] [CrossRef]
  34. Henry, M.L.; Hubbard, H.I.; Grasso, S.M.; Mandelli, M.L.; Wilson, S.M.; Sathishkumar, M.T.; Fridriksson, J.; Daigle, W.; Boxer, A.L.; Miller, B.L.; et al. Retraining speech production and fluency in non-fluent/agrammatic primary progressive aphasia. Brain 2018, 141, 1799–1814. [Google Scholar] [CrossRef] [PubMed]
  35. Pytel, V.; Cabrera-Martín, M.N.; Delgado-Álvarez, A.; Ayala, J.L.; Balugo, P.; Delgado-Alonso, C.; Yus, M.; Carreras, M.T.; Carreras, J.L.; Matías-Guiu, J.; et al. Personalized repetitive transcranial magnetic stimulation for primary progressive aphasia. J. Alzheimer’s Dis. 2021, 84, 151–167. [Google Scholar] [CrossRef]
  36. Montagut, N.; Borrego-Écija, S.; Castellví, M.; Rico, I.; Reñé, R.; Balasa, M.; Lladó, A.; Sánchez-Valle, R. Errorless learning therapy in semantic variant of primary progressive aphasia. J. Alzheimer’s Dis. 2021, 79, 415–422. [Google Scholar] [CrossRef] [PubMed]
  37. Huang, Y.; Tan, Y.; Hao, H.; Li, J.; Liu, C.; Hu, Y.; Wu, Y.; Ding, Q.; Zhou, Y.; Li, Y.; et al. Treatment of primary progressive aphasia by repetitive transcranial magnetic stimulation: A randomized, double-blind, placebo-controlled study. J. Neural Transm. 2023, 130, 111–123. [Google Scholar] [CrossRef] [PubMed]
  38. Borrego-Écija, S.; Montagut, N.; Martín-Trias, P.; Vaqué-Alcázar, L.; Illán-Gala, I.; Balasa, M.; Casanova-Mollà, J.; Bargalló, N.; Valls-Solé, J.; Lleó, A.; et al. Multifocal transcranial direct current stimulation in primary progressive aphasia does not provide a clinical benefit over speech therapy. J. Alzheimer’s Dis. 2023, 93, 1169–1180. [Google Scholar] [CrossRef]
  39. Schaffer, K.M.; Wauters, L.; Berstis, K.; Grasso, S.M.; Henry, M.L. Modified script training for nonfluent/agrammatic with significant hearing loss: A single-case experimental design. Neuropsychol. Rehabil. 2022, 32, 306–335. [Google Scholar] [CrossRef]
  40. Schaffer, K.M.; Evans, W.S.; Dutcher, C.D.; Philburn, C.; Henry, M.L. Embedding aphasia-modified cognitive behavioral therapy in script training for primary progressive aphasia: A single-case pilot study. Am. J. Speech-Lang. Pathol. 2021, 30, 2053–2068. [Google Scholar] [CrossRef]
  41. Meyer, A.M.; Tippett, D.C.; Friedman, R.B. Prophylaxis and remediation of anomia in the semantic and logopenic variants of primary progressive aphasia. Neuropsychol. Rehabil. 2016, 28, 352. [Google Scholar] [CrossRef]
  42. Meyer, A.M.; Tippett, D.C.; Turner, R.S.; Friedman, R.B. Long-term maintenance of anomia treatment effects in primary progressive aphasia. Neuropsychol. Rehabil. 2019, 29, 1439–1463. [Google Scholar] [CrossRef]
  43. Farrajota, L.; Maruta, C.; Maroco, J.; Martins, I.P.; Guerreiro, M.; de Mendonça, A. Speech therapy in primary progressive aphasia: A pilot study. Dement. Geriatr. Cogn. Disord. Extra 2012, 2, 321. [Google Scholar] [CrossRef]
  44. Cotelli, M.; Manenti, R.; Petesi, M.; Brambilla, M.; Cosseddu, M.; Zanetti, O.; Miniussi, C.; Padovani, A.; Borroni, B. Treatment of PPA by transcranial direct current stimulation combined with language training. J. Alzheimer’s Dis. 2014, 39, 799–808. [Google Scholar] [CrossRef] [PubMed]
  45. Dial, H.R.; Hinshelwood, H.; Grasso, S.M.; Hubbard, H.I.; Gorno-Tempini, M.-L.; Henry, M.L. Investigating the utility of teletherapy in individuals with primary progressive aphasia. Clin. Interv. Aging 2019, 14, 453–471. [Google Scholar] [CrossRef] [PubMed]
  46. Krajenbrink, T.; Croot, K.; Taylor-Rubin, C.; Nickels, L. Treatment for spoken and written word retrieval in the semantic variant of primary progressive aphasia. Neuropsychol. Rehabil. 2020, 30, 915–947. [Google Scholar] [CrossRef]
  47. Taylor-Rubin, C.; Nickels, L.; Croot, K. Exploring the effects of verb and noun treatment on verb phrase production in primary progressive aphasia: A series of single-case experimental design studies. Neuropsychol. Rehabil. 2022, 32, 1121–1163. [Google Scholar] [CrossRef]
  48. Gervits, F.; Ash, S.; Coslett, H.B.; Rascovsky, K.; Grossman, M.; Hamilton, R. Transcranial direct current stimulation for the treatment of PPA: An open-label pilot study. Brain Lang. 2016, 162, 35–41. [Google Scholar] [CrossRef] [PubMed]
  49. Jokel, R.; Kielar, A.; Anderson, N.D.; Black, S.E.; Rochon, E.; Graham, S.; Freedman, M.; Tang-Wai, D.F. Behavioural and neuroimaging changes after naming therapy for semantic variant primary progressive aphasia. Neuropsychologia 2016, 89, 191–216. [Google Scholar] [CrossRef]
  50. Meyer, A.M.; Snider, S.F.; Eckmann, C.B.; Friedman, R.B. Prophylactic treatments for anomia in the logopenic variant of primary progressive aphasia: Cross-language transfer. Aphasiology 2015, 29, 1062–1081. [Google Scholar] [CrossRef]
  51. Trebbastoni, A.; Raccah, R.; de Lena, C.; Zangen, A.; Inghilleri, M. Repetitive deep transcranial magnetic stimulation improves verbal fluency and written language in a patient with logopenic variant (lvPPA). Brain Stimul. 2013, 6, 545–553. [Google Scholar] [CrossRef]
  52. Meyer, A.M.; Getz, H.R.; Brennan, D.M.; Hu, T.M.; Friedman, R.B. Telerehabilitation of anomia in primary progressive aphasia. Aphasiology 2016, 30, 483–507. [Google Scholar] [CrossRef]
  53. Shah-Basak, P.; Fernandez, A.; Armstrong, S.E.M.; Hodzic-Santor, B.H.; Lavoie, M.; Jokel, R.; Meltzer, J.A. Behavioural and neurophysiological responses to written naming treatment and high definition tDCS: A case study in advanced primary progressive aphasia. Aphasiology 2022, 36, 1182–1205. [Google Scholar] [CrossRef]
  54. Hung, J.; Bauer, A.; Grossman, M.; Hamilton, R.H.; Coslett, H.B.; Reilly, J. Semantic feature training in combination with transcranial direct current stimulation (tDCS) for progressive anomia. Front. Hum. Neurosci. 2017, 11, 223285. [Google Scholar] [CrossRef]
  55. Themistocleous, C.; Webster, K.; Tsapkini, K. Effects of tDCS on sound duration in patients with apraxia of speech in primary progressive aphasia. Brain Sci. 2021, 11, 335. [Google Scholar] [CrossRef]
  56. Jafari, S.; Khatoonabadi, A.R.; Noroozian, M.; Mehri, A.; Ashayeri, H.; Nickels, L. The effect of word retrieval therapy in primary progressive aphasia: A single-case study. Arch. Neurosci. 2018, 5, e67577. [Google Scholar] [CrossRef]
  57. de Aguiar, V.; Rofes, A.; Wendt, H.; Ficek, B.N.; Webster, K.; Tsapkini, K. Treating lexical retrieval using letter fluency and tDCS in primary progressive aphasia: A single-case study. Aphasiology 2022, 36, 353–379. [Google Scholar] [CrossRef]
  58. Lavoie, M.; Bier, N.; Laforce, R.; Macoir, J. Improvement in functional vocabulary and generalization to conversation following a self-administered treatment using a smart tablet in primary progressive aphasia. Neuropsychol. Rehabil. 2020, 30, 1224–1254. [Google Scholar] [CrossRef] [PubMed]
  59. Croot, K.; Taylor, C.; Abel, S.; Jones, K.; Krein, L.; Hameister, I.; Ruggero, L.; Nickels, L. Measuring gains in connected speech following treatment for word retrieval: A study with two participants with primary progressive aphasia. Aphasiology 2015, 29, 1265–1288. [Google Scholar] [CrossRef]
  60. Tsapkini, K.; Frangakis, C.; Gomez, Y.; Davis, C.; Hillis, A.E. Augmentation of spelling therapy with transcranial direct current stimulation in primary progressive aphasia: Preliminary results and challenges. Aphasiology 2014, 28, 1112–1130. [Google Scholar] [CrossRef]
  61. Fenner, A.S.; Webster, K.T.; Ficek, B.N.; Frangakis, C.E.; Tsapkini, K. Written verb naming improves after tDCS over the left IFG in primary progressive aphasia. Front. Psychol. 2019, 10, 1396. [Google Scholar] [CrossRef]
  62. Henry, M.L.; Hubbard, H.I.; Grasso, S.M.; Dial, H.R.; Beeson, P.M.; Miller, B.L.; Gorno-Tempini, M.L. Treatment for word retrieval in semantic and logopenic variants of primary progressive aphasia: Immediate and long-term outcomes. J. Speech Lang. Hear. Res. 2019, 62, 2723–2749. [Google Scholar] [CrossRef]
  63. Henry, M.L.; Rising, K.; DeMarco, A.T.; Miller, B.; Gorno-Tempini, M.; Beeson, P. Examining the value of lexical retrieval treatment in PPA: Two positive cases. Brain Lang. 2013, 127, 145–156. [Google Scholar] [CrossRef]
  64. Kim, M. Effect of lexical retrieval cascade treatment on naming and discourse of individuals with logopenic variant of PPA. Clin. Arch. Commun. Disord. 2017, 2, 197. [Google Scholar] [CrossRef]
  65. Dressel, K.; Huber, W.; Frings, L.; Kümmerer, D.; Saur, D.; Mader, I.; Hüll, M.; Weiller, C.; Abel, S. Model-oriented naming therapy in semantic dementia: A single-case fMRI study. Aphasiology 2010, 24, 1537–1558. [Google Scholar] [CrossRef]
  66. Jokel, R.; Rochon, E.; Anderson, N.D. Errorless learning of computer-generated words in a patient with semantic dementia. Neuropsychol. Rehabil. 2010, 20, 16–41. [Google Scholar] [CrossRef]
  67. Senaha, M.L.H.; Brucki, S.M.D.; Nitrini, R. Rehabilitation in semantic dementia: Study of the effectiveness of lexical reacquisition in three patients. Dement. Neuropsychol. 2010, 4, 306–312. [Google Scholar] [CrossRef] [PubMed]
  68. Beeson, P.M.; King, R.M.; Bonakdarpour, B.; Henry, M.L.; Cho, H.; Rapcsak, S.Z. Positive effects of language treatment for the logopenic variant of primary progressive aphasia. J. Mol. Neurosci. 2011, 45, 724–736. [Google Scholar] [CrossRef]
  69. Mayberry, E.J.; Sage, K.; Ehsan, S.; Ralph, M.A.L. Relearning in semantic dementia reflects contributions from both medial temporal lobe episodic and degraded neocortical semantic systems. Neuropsychologia 2011, 49, 3591–3598. [Google Scholar] [CrossRef] [PubMed]
  70. Jokel, R.; Anderson, N.D. Quest for the best: Effects of errorless and active encoding on word re-learning in semantic dementia. Neuropsychol. Rehabil. 2012, 22, 187–214. [Google Scholar] [CrossRef]
  71. Henry, M.L.; Meese, M.V.; Truong, S.; Babiak, M.C.; Miller, B.L.; Gorno-Tempini, M.L. Treatment for apraxia of speech in nonfluent variant primary progressive aphasia. Behav. Neurol. 2013, 26, 77–88. [Google Scholar] [CrossRef]
  72. Hoffman, P.; Clarke, N.; Jones, R.W.; Noonan, K.A. Vocabulary relearning in semantic dementia: Positive and negative consequences of increasing variability in the learning experience. Neuropsychologia 2015, 76, 240–253. [Google Scholar] [CrossRef]
  73. Suárez-González, A.; Heredia, C.G.; Savage, S.A.; Gil-Néciga, E.; García-Casares, N.; Franco-Macías, E.; Berthier, M.L.; Caine, D. Restoration of conceptual knowledge in a case of semantic dementia. Neurocase 2015, 21, 309–321. [Google Scholar] [CrossRef]
  74. Roncero, C.; Kniefel, H.; Service, E.; Thiel, A.; Probst, S.; Chertkow, H. Inferior parietal transcranial direct current stimulation with training improves cognition in anomic Alzheimer’s disease and frontotemporal dementia. Alzheimer’s Dement. Transl. Res. Clin. Interv. 2017, 3, 247–253. [Google Scholar] [CrossRef]
  75. Ficek, B.N.; Wang, Z.; Zhao, Y.; Webster, K.T.; Desmond, J.E.; Hillis, A.E.; Frangakis, C.; Faria, A.V.; Caffo, B.; Tsapkini, K. The effect of tDCS on functional connectivity in primary progressive aphasia. NeuroImage Clin. 2018, 19, 703–715. [Google Scholar] [CrossRef] [PubMed]
  76. Grasso, S.M.; Shuster, K.M.; Henry, M.L. Comparing the effects of clinician and caregiver-administered lexical retrieval training for progressive anomia. Neuropsychol. Rehabil. 2019, 29, 866–895. [Google Scholar] [CrossRef] [PubMed]
  77. Meyer, A.M.; Faria, A.V.; Tippett, D.C.; Hillis, A.E.; Friedman, R.B. The relationship between baseline volume in temporal areas and post-treatment naming accuracy in primary progressive aphasia. Aphasiology 2017, 31, 1059–1077. [Google Scholar] [CrossRef]
  78. Suárez-González, A.; Savage, S.A.; Caine, D. Successful short-term re-learning and generalisation of concepts in semantic dementia. Neuropsychol. Rehabil. 2018, 28, 1095–1109. [Google Scholar] [CrossRef]
  79. Croot, K.; Raiser, T.; Taylor-Rubin, C.; Ruggero, L.; Ackl, N.; Wlasich, E.; Danek, A.; Scharfenberg, A.; Foxe, D.; Hodges, J.R.; et al. Lexical retrieval treatment in primary progressive aphasia: An investigation of treatment duration in a heterogeneous case series. Cortex 2019, 115, 133–158. [Google Scholar] [CrossRef]
  80. Cotelli, M.; Manenti, R.; Paternicò, D.; Cosseddu, M.; Brambilla, M.; Petesi, M.; Premi, E.; Gasparotti, R.; Zanetti, O.; Padovani, A.; et al. Grey matter density predicts the improvement of naming abilities after tDCS intervention in agrammatic variant of primary progressive aphasia. Brain Topogr. 2016, 29, 738–751. [Google Scholar] [CrossRef]
  81. Sayadnasiri, M.; Dieji, B.; Noroozi, M.; Rezaei, O. The effect of zolpidem on language function of patients with nonfluent variant of frontotemporal dementia: A pilot study. Clin. Neuropharmacol. 2021, 44, 81–84. [Google Scholar] [CrossRef]
  82. Wang, Z.; Ficek, B.N.; Webster, K.T.; Herrmann, O.; Frangakis, C.E.; Desmond, J.E.; Onyike, C.U.; Caffo, B.; Hillis, A.E.; Tsapkini, K. Specificity in generalization effects of transcranial direct current stimulation over the left inferior frontal gyrus in primary progressive aphasia. Neuromodul. Technol. Neural Interface 2023, 26, 850–860. [Google Scholar] [CrossRef]
  83. Lerman, A.; Mais, D.; Nissani, Y.; Malcolm, T. Preserving lexical retrieval skills across languages in a bilingual person with logopenic primary progressive aphasia. Aphasiology 2023, 37, 432–455. [Google Scholar] [CrossRef]
  84. Watanabe, M.; Cartwright, J.; Pierce, J.E. Positive effects of speech and language therapy group interventions in primary progressive aphasia: A systematic review. Int. J. Lang. Commun. Disord. 2024, 59, 1832–1849. [Google Scholar] [CrossRef]
  85. Cotelli, M.; Manenti, R.; Ferrari, C.; Gobbi, E.; Macis, A.; Cappa, S.F. Effectiveness of language training and non-invasive brain stimulation on oral and written naming performance in primary progressive aphasia: A meta-analysis and systematic review. Neurosci. Biobehav. Rev. 2020, 108, 498–525. [Google Scholar] [CrossRef]
  86. Nissim, N.R.; Moberg, P.J.; Hamilton, R.H. Efficacy of noninvasive brain stimulation (tDCS or TMS) paired with language therapy in the treatment of primary progressive aphasia: An exploratory meta-analysis. Brain Sci. 2020, 10, 597. [Google Scholar] [CrossRef]
  87. Lomi, F.; Simonelli, I.; Cappa, S.; Pasqualetti, P.; Rossi, S. Noninvasive brain stimulation in primary progressive aphasia with and without concomitant speech and language therapy: Systematic review and meta-analysis. Neuropsychol. Rev. 2025, 1–27. [Google Scholar] [CrossRef]
  88. Tee, B.L.; Gorno-Tempini, M.L. Primary progressive aphasia: A model for neurodegenerative disease. Curr. Opin. Neurol. 2019, 32, 255–265. [Google Scholar] [CrossRef]
  89. Grossman, M. The non-fluent/agrammatic variant of primary progressive aphasia. Lancet Neurol. 2012, 11, 545–555. [Google Scholar] [CrossRef]
  90. Mesulam, M.M.; Coventry, C.; Bigio, E.H.; Geula, C.; Thompson, C.; Bonakdarpour, B.; Gefen, T.; Rogalski, E.J.; Weintraub, S. Nosology of primary progressive aphasia and the neuropathology of language. Adv. Exp. Med. Biol. 2021, 1281, 33–49. [Google Scholar] [CrossRef]
  91. Goldberg, Z.-L.; El-Omar, H.; Foxe, D.; Leyton, C.E.; Ahmed, R.M.; Piguet, O.; Irish, M. Cognitive and neural mechanisms of social communication dysfunction in primary progressive aphasia. Brain Sci. 2021, 11, 1600. [Google Scholar] [CrossRef]
  92. Europa, E.; Iaccarino, L.; Perry, D.C.; Weis, E.; Welch, A.E.; Rabinovici, G.D.; Miller, B.L.; Gorno-Tempini, M.L.; Henry, M.L. Diagnostic assessment in primary progressive aphasia: An illustrative case example. Am. J. Speech-Lang. Pathol. 2020, 29, 1833–1849. [Google Scholar] [CrossRef]
  93. Mazzeo, S.; Morinelli, C.; Polito, C.; Giacomucci, G.; Moschini, V.; Ingannato, A.; Balestrini, J.; Frigerio, D.; Emiliani, F.; Galdo, G.; et al. Data-driven subtypes of mixed semantic-logopenic PPA: Linguistic features, biomarker profiles and brain metabolic patterns. J. Neurol. Sci. 2024, 460, 122998. [Google Scholar] [CrossRef]
  94. Mesulam, M. Primary progressive aphasia: A dementia of the language network. Dement. Neuropsychol. 2013, 7, 2–9. [Google Scholar] [CrossRef]
  95. Carlos, A.F.; Josephs, K.A. Frontotemporal lobar degeneration with TAR DNA-binding protein 43 (TDP-43): Its journey of more than 100 years. J. Neurol. 2022, 269, 4030–4054. [Google Scholar] [CrossRef] [PubMed]
  96. Sitek, E.J.; Narożańska, E.; Brockhuis, B.; Muraszko-Klaudel, A.; Lass, P.; Harciarek, M.; Sławek, J. Neuroimaging in the differential diagnosis of primary progressive aphasia–Illustrative case series in the light of new diagnostic criteria. Pol. J. Radiol. 2014, 79, 251. [Google Scholar] [CrossRef]
  97. Roytman, M.; Chiang, G.; Gordon, M.; Franceschi, A. Multimodality imaging in primary progressive aphasia. Am. J. Neuroradiol. 2022, 43, 1230–1243. [Google Scholar] [CrossRef]
  98. Caso, F.; Mandelli, M.L.; Henry, M.; Gesierich, B.; Bettcher, B.M.; Ogar, J.; Filippi, M.; Comi, G.; Magnani, G.; Sidhu, M.; et al. In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by FTLD pathology. Neurology 2014, 82, 239–247. [Google Scholar] [CrossRef]
  99. Mendez, M.F.; Nasir, I. Distinguishing semantic variant primary progressive aphasia from Alzheimer’s disease. J. Alzheimer’s Dis. Rep. 2023, 7, 227–234. [Google Scholar] [CrossRef]
  100. Momota, Y.; Konishi, M.; Takahata, K.; Kishimoto, T.; Tezuka, T.; Bun, S.; Tabuchi, H.; Ito, D.; Mimura, M. Case report: Non-Alzheimer’s disease tauopathy with logopenic variant primary progressive aphasia diagnosed using amyloid and tau PET. Front. Neurol. 2022, 13, 1049113. [Google Scholar] [CrossRef]
  101. Henry, M.L.; Gorno-Tempini, M.L. The logopenic variant of primary progressive aphasia. Curr. Opin. Neurol. 2010, 23, 633–637. [Google Scholar] [CrossRef]
  102. Gkintoni, E.; Michou, E. Advancing neuropsychological rehabilitation in primary progressive aphasia based on principles of cognitive neuroscience: A scoping review and systematic analysis of the data. Brain Sci. 2024, 14, 1234. [Google Scholar] [CrossRef]
  103. Schaeverbeke, J.; Evenepoel, C.; Bruffaerts, R.; Van Laere, K.; Bormans, G.; Dries, E.; Tousseyn, T.; Nelissen, N.; Peeters, R.; Vandenbulcke, M.; et al. Cholinergic depletion and basal forebrain volume in primary progressive aphasia. NeuroImage Clin. 2017, 13, 271–279. [Google Scholar] [CrossRef]
  104. Members of the Task Force on Cognitive Rehabilitation; Cappa, S.F.; Benke, T.; Clarke, S.; Rossi, B.; Stemmer, B.; van Heugten, C.M. EFNS guidelines on cognitive rehabilitation: Report of an EFNS task force. Eur. J. Neurol. 2005, 12, 665–680. [Google Scholar] [CrossRef]
  105. Gallée, J.; Volkmer, A. Role of the speech-language therapist/pathologist in primary progressive aphasia. Neurol. Clin. Pract. 2023, 13, e200178. [Google Scholar] [CrossRef]
  106. Elsahar, Y.; Hu, S.; Bouazza-Marouf, K.; Kerr, D.; Mansor, A. Augmentative and alternative communication (AAC) advances: A review of configurations for individuals with a speech disability. Sensors 2019, 19, 1911. [Google Scholar] [CrossRef]
  107. Robinaugh, G.; Henry, M.L. Behavioral interventions for primary progressive aphasia. Handb. Clin. Neurol. 2022, 185, 221–240. [Google Scholar] [CrossRef]
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Figure 1. Prisma flow diagram outlining literature review and study selection process.
Figure 1. Prisma flow diagram outlining literature review and study selection process.
Jcm 14 03063 g001
Table 1. Study Characteristics.
Table 1. Study Characteristics.
StudyPublication YearCountryStudy DesignPopulationPPA SubtypeTherapy UsedTreatment DurationAge, Mean (SD) or RangeGender (M/F)
Tsapkinia [28]2018USARandomized controlled trial36nfvPPA: 14, svPPA: 10, lvPPA: 12tDCS and language/spelling therapy6 wN/A20/16
Rogalski [29]2022USAProspective experimental study49nfvPPA: 15, svPPA: 4, lvPPA: 18, other variants: 12Speech-language therapyN/A67.1 (7.3)25/24
Joubert [30]2023CanadaSingle case experimental study1svPPA: 1Smartphone-based cognitive and picture naming therapy5 W660/1
Meyer [31]2023USAProspective experimental study37N/APhonological and orthographic treatmentN/A70.61 (7.49)N/A
Aguiar [32]2020USARandomized controlled trial40nfvPPA: 15, lvPPA: 17, svPPA: 8Picture naming, spelling and tDCS3 W67.68 (6.76)22/18
Nissim [33]2022USAProspective experimental study12lvPPA: 8, svPPA: 2, nfvPPA: 2HD-tDCS and CILT4 W66.92 (6.37)8/4
Henry [34]2018USAProspective experimental study10nfvPPA: 10VISTAN/A67.70 (5.5)4/6
Pytel [35]2021SpainRandomized controlled trial20nfvPPA: 16, svPPA: 4rTMS10 wN/A8/12
Montagut [36]2021SpainProspective experimental study8svPPA: 8Errorless learning therapy8 w64 (10.5)4/4
Huang [37]2023ChinaRandomized controlled trial40nfvPPA: 16, svPPA: 12, lvPPA: 12 (20 patients in control, and 20 patients in intervention)rTMS 4 w65.2 (6.6)19/21
Borrego-Ecija [38]2023SpainRandomized controlled trial15svPPA: 4, lvPPA: 5, nfvPPA: 6tDCS and speech therapy4 w63 (8.4)5/10
Schaffer [39]2022USASingle case experimental study1nfvPPA: 1VISTA6 w721/0
Schaffer [40]2021USASingle case experimental study1nfvPPA: 1Spontaneous speech and fluency therapy6 w780/1
Meyer [41]2018USAProspective experimental study14svPPA: 5, lvPPA: 9Phonological and orthographic treatment24 w65.6 (5.3)5/9
Meyer [42]2019USAProspective experimental study26svPPA: 5, lvPPA: 9, nfvPPA: 12Phonological and orthographic treatment24 w69.2 (8.1)12/14
Farrajota [43]2012PortugalProspective experimental study20Intervention: nfvPPA: 2, svPPA: 2, lvPPA: 6 Control: nfvPPA: 0, svPPA: 6, lvPPA: 4SLTN/A68 (7.8)14/6
Cotelli [44]2014ItalyRandomized controlled trial16lvPPA: 16tDCS and ICAT2 w66.9 (8.2)6/10
Dial [45]2019USANon-randomized trial31nfvPPA: 10, svPPA: 10, lvPPA: 11LRT and VISTAN/A67.6 (3.9)13/18
Krajenbrink [46]2020AustraliaSingle case experimental study1svPPA: 1RRIPP and COEN6 w601/0
Tylor-Rubin [47]2022AustraliaCase series4svPPA: 3, lvPPA: 1RRIPP6 w69.25 (5.2)0/4
Gervits [48]2016USAProspective experimental study6lvPPA: 4, nfvPPA: 2tDCS2 w66.2 (5.7)1/5
Rogalski [17]2016USAProspective experimental study31N/ASLT8 w67.2 (6.9)13/18
Jokel [49]2016CanadaCase Series4svPPA: 4Errorless learning therapy10 w61.25 (7.75)N/A
Meyer [50]2015USASingle case experimental study1lvPPA: 1Phonological and orthographic treatment48 w690/1
Trebbastoni [51]2013ItalySingle case experimental study1lvPPA: 1hf-rTMS20 s501/0
Meyer [52]2016USACase series3nfvPPA: 1, svPPA: 1, lvPPA: 1Phonological and orthographic treatment24 w61.61/2
Shah-Basak [53]2022CanadaSingle case experimental study1nfvPPA: 1Written naming and HD-tDCS2 w671/0
Hung [54]2017USAProspective experimental study4svPPA: 3, lvPPA: 1Semantic feature training and tDCS2 w66.6 (8.56)3/2
Themistocleous [55]2021USAProspective experimental study8nfvPPA with AOS: 8tDCS and speech therapy6 w66 (8.3)4/4
Jafari [56]2018IranSingle case experimental study1nfvPPA with AOS: 1Cueing hierarchy and story-retelling therapy8 w560/1
Aguiar [56]2022USASingle case experimental study1lvPPA: 1LeFT and anodal tDCS12 w721/0
Lavoie [58]2020CanadaCase series 5svPPA: 2, lvPPA: 3Tablet-based SFA4 w722/3
Croot [59]2015AustraliaCase series 2lvPPA: 2RRIPP2 w67 (13)1/1
Tsapkini [60]2014USACrossover trial 6nfvPPA: 2, lvPPA: 4tDCSN/AN/A3/3
Fenner [61]2019USARandomized controlled trial11nfvPPA: 6, lvPPA: 5tDCS and verb naming and spelling therapyN/A67.6 (7.7)5/6
Henry [62]2019USAProspective experimental study18svPPA: 9, lvPPA: 9LRT12 w65.28 (8.32)7/11
Henry [63]2013USACase series 2svPPA: 1, lvPPA: 1Structured oral reading therapy12 w57 (3)0/1
Kim [64]2017USACase series 2lvPPA: 2LRCN/A68.5 (5.5)N/A
Dressel [65]2010GermanySingle case experimental study1svPPA: 1Naming therapy and cueing hierarchies4 w481/0
Jokel [66]2010CanadaSingle case experimental study1svPPA: 1Errorless learning therapy12 wN/A1/0
Senaha [67]2010BrazilSingle case experimental study3svPPA: 3Lexical reacquisition (errorless learning)24–72 w62.66 (10.14)2/1
Beeson [68]2011USASingle case experimental study1lvPPA: 1Semantic retrieval therapy2 w771/0
Mayberry [69]2011UKProspective experimental study2svPPA: 2Relearning therapy3 w58.5 (6.5)1/1
Jokel [70]2012CanadaProspective experimental study7svPPA: 7Errorless learning therapy8–12 w68.28 (9.96)3/4
Henry [71]2013USASingle case experimental study1lvPPA: 1LRC4 w732/0
Hoffman [72]2015UKCase series3svPPA: 3Vocabulary relearning3 w59.57 (2.87)0/3
Suárez-González [73]2015Spain, UK, AustraliaSingle case experimental study1svPPA: 1COEN and naming Therapy12 w570/1
Roncero [74]2017CanadaRandomized controlled trial10nfvPPA: 6, svPPA: 2, lvPPA: 2tDCS and object naming3 w67.4 (5.9)7/3
Ficek [75]2018USARandomized controlled trial36Intervention: nfvPPA: 5, lvPPA: 9, svPPA: 3, Control: nfvPPA: 8, lvPPA: 6, svPPA: 5tDCS and language therapy6 w67.2 (6.5)13/11
Grasso [76]2019USASingle case experimental study2Mixed PPA: 1, Mild cognitive Impairment: 1LRTN/A72.5 (6.5)1/1
Meyer [77]2017USACase series21lvPPA: 9, svPPA: 5, nfvPPA: 7Orthographic treatment24 w69.1 (2.3)10/11
Suárez-González [78]2011UKSingle case experimental study1svPPA: 1COEN and naming therapy1 w620/1
Croot [79]2019AustraliaCase series8nfvPPA: 3, lvPPA: 2, svPPA: 2, Mixed PPA: 1LRT2–4 w64.87 (5.5)3/5
Cotelli [80]2016ItalyCase series18nfvPPA: 18tDCSN/A66.5 (9.5)9/9
Sayadnasiri [81]2021IranSingle case experimental study13nfvPPA: 13Zolpidem6 w58.5 (4.5)8/5
Wang [82]2023USARandomized controlled trial36lvPPA: 14, nfvPPA: 13, svPPA: 9tDCS and lexical/semantic therapy8 w50–8019/17
Lerman [83]2023IsraelSingle case experimental study1lvPPA: 1VNeST10 w700/1
PPA: primary progressive aphasia; nfvPPA: nonfluent/agrammatic variant primary progressive aphasia; svPPA: semantic variant; lvPPA: logopenic variation of primary progressive aphasia; tDCS: transcranial direct current stimulation; HD-tDCS: high-definition transcranial direct current stimulation; rTMS: repetitive transcranial magnetic stimulation; hf-rTMS: high-frequency repetitive transcranial magnetic stimulation; SLT: speech-language therapy; CILT: constraint-induced language therapy; ICAT: intensive comprehensive aphasia therapy; VISTA: video-implemented script training for aphasia; LRC: lexical retrieval cascade; LRT: lexical retrieval therapy; RRIPP: repetitive rehabilitation for impaired phonological processing; COEN: cognitive and executive naming; LeFT: lexical feature training; AOS: apraxia of speech; SFA: semantic feature analysis; VNeST: verb network strengthening treatment; N/A: not available or not applicable; M/F: male/female; SD: standard deviation.
Table 2. Risk of bias assessment for RCTs and crossover trials (Cochrane RoB 2 Tool).
Table 2. Risk of bias assessment for RCTs and crossover trials (Cochrane RoB 2 Tool).
First AuthorYearSelection BiasPerformance BiasDetection BiasAttrition BiasReporting BiasOverall Risk
Tsapkinia [28]2018LowSome ConcernsLowLowLowLow
Aguiar [32]2020LowLowLowSome ConcernsLowSome Concerns
Cotelli [44]2014LowLowSome ConcernsLowLowLow
Huang [37]2023LowLowLowLowSome ConcernsLow
Borrego-Ecija [38]2023Some ConcernsSome ConcernsLowLowLowSome Concerns
Pytel [37]2021LowSome ConcernsLowSome ConcernsLowSome Concerns
Roncero [74]2017LowLowLowLowLowLow
Ficek [75]2018LowLowLowLowSome ConcernsLow
Wang [82]2023LowSome ConcernsLowLowLowSome Concerns
RoB 2: Cochrane risk of bias tool 2; RCTs: randomized controlled trials.
Table 3. Risk of bias assessment for non-randomized and experimental studies (ROBINS-I Tool).
Table 3. Risk of bias assessment for non-randomized and experimental studies (ROBINS-I Tool).
First AuthorYearBias Due to ConfoundingSelection BiasClassification BiasDeviations from Intended InterventionsMissing DataMeasurement BiasReporting BiasOverall Risk
Rogalski [29]2022ModerateModerateLowSome ConcernsLowLowSome ConcernsModerate
Meyer [31]2023ModerateLowSome ConcernsSome ConcernsLowLowSome ConcernsModerate
Nissim [33]2022ModerateSome ConcernsLowLowSome ConcernsLowSome ConcernsModerate
Henry [34]2018ModerateLowLowSome ConcernsLowLowSome ConcernsModerate
Montagut [36]2021HighSome ConcernsLowSome ConcernsSome ConcernsLowHighHigh
Henry [62]2019ModerateLowSome ConcernsSome ConcernsLowLowSome ConcernsModerate
Themistocleous [55]2021ModerateLowLowSome ConcernsLowLowLowModerate
Sayadnasiri [81]2021HighSome ConcernsLowSome ConcernsLowLowHighHigh
Lerman [83]2023ModerateLowSome ConcernsLowLowLowSome ConcernsModerate
ROBINS-I: Risk of bias in non-randomized studies of interventions.
Table 4. Risk of bias assessment for single-case designs and case series (JBI Checklist).
Table 4. Risk of bias assessment for single-case designs and case series (JBI Checklist).
First AuthorYearPatient SelectionIntervention Clearly DescribedOutcome Measures ReliableFollow-Up AdequateEthical ConsiderationsOverall Quality
Joubert [30]2023YesYesYesNoYesModerate
Schaffer [39]2022YesYesNoNoYesLow
Schaffer [40]2021YesYesYesNoYesModerate
Meyer [41]2018YesYesYesNoYesModerate
Meyer [42]2019YesYesYesNoYesModerate
Farrajota [43]2012NoYesYesNoYesLow
Dial [45]2019YesYesYesNoYesModerate
Krajenbrink [46]2020NoYesNoNoYesLow
Taylor-Rubin [47]2022YesYesYesNoYesModerate
Gervits [48]2016NoYesNoNoYesLow
Rogalski [17]2016NoYesNoNoYesLow
Jokel [49]2016YesYesYesNoYesModerate
Meyer [50]2015NoYesNoNoYesLow
Trebbastoni [51]2013NoYesNoNoYesLow
Meyer [52]2016NoYesNoNoYesLow
Shah-Basak [53]2022YesYesYesNoYesModerate
Hung [54]2017YesYesYesNoYesModerate
Beeson [68]2011YesYesYesNoYesModerate
Henry [71]2013NoYesNoNoYesLow
Hoffman [72]2015NoYesNoNoYesLow
Suárez-González [73]2015NoYesNoNoYesLow
Roncero [74]2017YesYesYesNoYesModerate
JBI: Joanna Briggs Institute.
Table 5. Summary of implemented intervention and their outcomes in PPA.
Table 5. Summary of implemented intervention and their outcomes in PPA.
OutcomesTherapy UsedAuthorsPPA SubtypeFollow-UpResults (Intervention vs. Control)
Letter (naming) accuracy during spelling of trained wordstDCS and language/spelling therapyTsapkinia 2018 [28]nfvPPA: 14, svPPA: 10, lvPPA: 12Post-TreatmentIntervention group language gains were improved and maintained significantly
2 weeks
2 months
Ficek 2018 [75]Intervention: nfvPPA: 5, lvPPA: 9, svPPA: 3 Control: nfvPPA: 8, lvPPA: 6, svPPA: 5Post-Treatment
tDCS and picture naming and spelling therapyAguiar 2022 [57]lvPPA: 1Post-Treatment
2-weeks
2-months
tDCS and lexical/semantic therapyWang 2023 [82]lvPPA: 14, nfvPPA: 13, svPPA: 9Post-treatment
2 weeks
2 months
Phonological and orthographic treatmentMeyer 2018 [41]svPPA: 5, lvPPA: 9Post-Treatment
Errorless learning therapyJokel 2012 [70]svPPA: 7Post-Treatment
Letter (naming) accuracy during spelling of untrained wordstDCS and language/spelling therapyTsapkinia 2018 [28]nfvPPA: 14, svPPA: 10, lvPPA: 12Post-Treatment
2 weeks
2 Months
tDCS and picture naming and spellingAguiar 2022 [57]lvPPA: 1Post-Treatment
2-weeks
2-months
Reading accuracyrTMSPytel 2021 [35]nfvPPA: 16, svPPA: 4Post-Treatment
tDCS and speech therapyBorrego-Ecija 2023 [38]svPPA: 4, lvPPA: 5, nfvPPA: 6Post-Treatment
Structured oral reading therapyHenry 2013 [71]lvPPA: 1Post-TreatmentReading accuracy improved after therapy implementation
3-months
6-months
1-year
Production of correct, intelligible scripted words (Speech)VISTAHenry 2018 [34]nfvPPA: 10Post-TreatmentSubstantial improvement and maintenance in production of scripted word
3-months
6-months
1-year
VISTASchaffer 2022 [39]nfvPPA: 1Post-Treatment
3-months
6-months
1-year
Spontaneous speech and fluencySmartphone-based cognitive and picture namingJoubert 2023 [30]svPPA: 1Post-TreatmentIntervention group showed positive reinforcement of spontaneous speech and fluency with different generalization and maintenance reinforcements
6-months
HD-tDCS and CILTNissim 2022 [33]lvPPA: 8, svPPA: 2, nfvPPA: 2Post-Treatment
6-weeks
tDCS and speech therapyBorrego-Ecija 2023 [38]svPPA: 4, lvPPA: 5, nfvPPA: 6Post-Treatment
Semantic feature training and tDCSHung 2017 [54]svPPA: 3, lvPPA: 1Post-Treatment
6-months
tDCS and speech therapyThemistocleous 2021 [55]nfvPPA with AOS: 8Post-Treatment
2-months
tDCSGervits 2016 [48]lvPPA: 4, nfvPPA: 22-weeks
6-weeks
12-weeks
LeFT and anodal tDCSAguiar 2022 [57]lvPPA: 1Post-Treatment
2-weeks
2-months
tDCSTsapkini 2014 [60]nfvPPA: 2, lvPPA: 4Post-Treatment
2-weeks
2-months
rTMSPytel 2021 [36]nfvPPA: 16, svPPA: 4Post-Treatment
hf-rTMSTrebbastoni 2013 [51]lvPPA: 1Post-Treatment
VISTAHenry 2018 [34]nfvPPA: 101-year
VISTASchaffer 2022 [39]nfvPPA: 1Post-Treatment
Spontaneous speech and fluencySchaffer 2021 [40]nfvPPA: 1Post-Treatment
3-months
6-months
1-year
Errorless learning therapyJokel 2016 [49]svPPA: 4Post-Treatment
Phonological and orthographic treatmentMeyer 2016 [41]svPPA: 5, lvPPA: 91-month
Cueing hierarchy and story-retelling therapy Jafari 2018 [56]nfvPPA with AOS: 1Post-Treatment
RRIPPCroot 2015 [59]lvPPA: 2Patient 1: Post-Treatment, 1-month
Patient 2: Post-Treatment, 9-months
Structured oral reading therapyHenry 2013 [71]lvPPA: 1Post-Treatment
3-months
6-months
1-year
LRCKim 2017 [64]lvPPA: 2Post-Treatment
2-months
AOSVISTAHenry 2018 [34]nfvPPA: 10Post-TreatmentIntervention group showed significant improvement in speech accuracy that was maintained post-treatment
3-months
6-months
1-year
Schaffer 2022 [39] nfvPPA: 1Post-Treatment
3-months
6-months
1-year
Dial 2019 [45]nfvPPA: 10, svPPA: 10, lvPPA: 11Post-Treatment
3-months
6-months
1-year
Structured oral reading therapyHenry 2013 [71] lvPPA: 1Post-Treatment
3-months
6-months
1-year
Meyer 2016 [52]nfvPPA: 1, svPPA: 1, lvPPA: 11-month
LeFT and tDCSAguiar 2022 [57]lvPPA: 1Post-Treatment
2-weeks
2-months
tDCS+ speech therapyThemistocleous 2021 [55]nfvPPA with AOS: 8Post-Treatment
2-months
rTMSPytal 2021 [35]nfvPPA: 16, svPPA 4Post-Treatment
HD-tDCS and story retelling with cueing hierarchyJafari 2018 [56]nfvPPA with AOS: 1Post-Treatment
Shah-Basak 2022 [53]nfvPPA: 15-days
3-months
Word retrievaltDCS and language therapyTsapkinia 2018 [28] nfvPPA: 14, svPPA: 10, lvPPA: 12Post-TreatmentIntervention group showed significant improvement in word retrieval potential that was maintained post-treatment
2-weeks
2-months
Cotelli 2014 [44] lvPPA: 162-weeks
12-weeks
Roncero 2017 [74] nfvPPA: 6,
svPPA: 2, lvPPA: 2		2-weeks
Ficek 2018 [75]Intervention:nfvPPA: 5, lvPPA: 9, svPPA: 3 Control: nfvPPA: 8, lvPPA: 6, svPPA: 5Post-Treatment
Huang 2023 [37] nfvPPA: 16, svPPA: 12, lvPPA: 12 (20 patients in control, and 20 patients in intervention)1-month
3-months
6-months
Borrego-Ecija 2023 [38]svPPA: 4, lvPPA: 5, nfvPPA: 6Post-Treatment
Tsapkini 2014 [60]nfvPPA: 2, lvPPA: 4Post-Treatment
2-weeks
2-months
Gervits 2016 [47] lvPPA: 4, nfvPPA: 22-weeks
6-weeks
12-weeks
Lerman 2023 [83]lvPPA: 1Post-Treatment
Wang 2023 [82]lvPPA: 14, nfvPPA: 13, svPPA: 9Post-Treatment
2-weeks
2-months
SLTRogalski 2022 [30]nfvPPA: 15, svPPA: 4, lvPPA: 18, other variants: 122-months
6-months
Farrajota 2012 [43]Intervention: nfvPPA: 2, svPPA: 2, lvPPA: 6 Control: nfvPPA: 0, svPPA: 6, lvPPA: 4Post-Treatment
Henry 2019 [62]svPPA: 9, lvPPA: 9Post-Treatment
3-months
6-months
1-year
Jokel 2016 [49]svPPA: 4Post-Treatment
Meyer 2017 [77]lvPPA: 9, svPPA: 5, nfvPPA: 71-month
tDCS and spelling/picture namingAguiar 2020 [32] nfvPPA: 15, lvPPA: 17, svPPA: 8Post-Treatment
2-weeks
2-months
Croot 2019 [79]nfvPPA: 3, lvPPA: 2, svPPA: 2, Mixed PPA: 1Post-Treatment
Borrego-Ecija 2023 [38]svPPA: 4, lvPPA: 5, nfvPPA: 6Post-Treatment
Phonological and orthographic treatmentMeyer 2018 [41]svPPA: 5, lvPPA: 9Post-Treatment
Meyer 2019 [42]svPPA: 5,
lvPPA: 9, nfvPPA: 12		1-month
Meyer 2015 [50]lvPPA: 11-week
8-months
1-year
20-months
3-years
Huang 2023 [37]nfvPPA: 16, svPPA: 12, lvPPA: 12 (20 patients in control, and 20 patients in intervention)1-month
3-months
6-months
Errorless learning therapyJokel 2010 [66]svPPA: 1Post-Treatment
Montagut 2021 [36]svPPA: 8Post-Treatment
1-month
3-months
6-months
Gervits 2016 [48]lvPPA: 4, nfvPPA: 22-weeks
6-weeks
12-weeks
LRCBeeson 2011 [68]lvPPA: 1Post-Treatment
3-weeks
4-months
6-months
Henry 2013 [63]lvPPA: 1, svPPA: 1Post-Treatment
3-months
6-months
1-year
Meyer 2015 [50]lvPPA: 11-week
8-months
1-year
20-months
3-years
Grasso 2019 [70]svPPA: 7Post-Treatment
3-months
6-months
Henry 2018 [34]nfvPPA: 10Post-Treatment
3-months
6-months
1-year
tDCS and CILT Nissim 2022 [33]lvPPA: 8, svPPA: 2, nfvPPA: 2Post-Treatment
6-weeks
Semantic feature training and tDCSHung 2017 [54]svPPA: 3, lvPPA: 1Post-Treatment
6-months
Lavoie 2020 [58]svPPA: 2, lvPPA: 3Post-Treatment
RRIPP and COENKrajenbrink 2020 [46]svPPA: 1Post-Treatment
2-weeks
Tylor-Rubin 2022 [47]svPPA: 3, lvPPA: 1Post-Treatment
VISTAHenry 2018 [34]nfvPPA: 10Post-Treatment
3-months
6-months
1-year
Henry 2019 [66]svPPA: 9, lvPPA: 9Post-Treatment
3-months
6-months
1-year
Schaffer 2022 [39]nfvPPA: 1Post-Treatment
3-months
6-months
1-year
Smartphone-based cognitive and picture namingJoubert 2023 [30]svPPA: 1Post-Treatment
6-months
rTMS Pytel 2021 [36]nfvPPA: 16, svPPA: 4Post-Treatment
Reading abilitiesPhonological and orthographic treatmentMeyer 2019 [42]svPPA: 5,
lvPPA: 9, nfvPPA: 12		1-monthIntervention group showed significant improvement in reading accuracy that was maintained post-treatment at various intervals
Meyer 2018 [41]svPPA: 5, lvPPA: 9Post-Treatment
Henry 2013 [63]svPPA: 1, lvPPA: 1Post-Treatment
3-months
6-months
1-year
Errorless learning therapyJokel 2010 [66]svPPA: 1Post-Treatment
Senaha 2010 [67]svPPA: 3Post-Treatment
Montagut 2021 [36]svPPA: 8Post-Treatment
1-month
3-months
6-months
rTMSPytel 2021 [35]nfvPPA: 16, svPPA: 4Post-Treatment
Henry 2019 [62]svPPA: 9, lvPPA: 9Post-Treatment
3-months
6-months
1-year
Repetition abilitiestDCS and language therapyTsapkinia 2018 [28] nfvPPA: 14, svPPA: 10, lvPPA: 12Post-TreatmentIntervention group showed improvement in reading accuracy that was maintained post-treatment at various intervals, some studies reported mixed results
2-weeks
2-months
Cotelli 2016 [80] Post-Treatment
3-months
Ficek 2018 [75]Intervention: nfvPPA: 5, lvPPA: 9, svPPA: 3 Control: nfvPPA: 8, lvPPA: 6, svPPA: 5Post-Treatment
Gervits 2016 [48]lvPPA: 4, nfvPPA: 22-weeks
6-weeks
12-weeks
Roncero 2017 [74]nfvPPA: 6,
svPPA: 2, lvPPA: 2		2-weeks
Fenner 2019 [61]nfvPPA: 6, lvPPA: 5Post-Treatment
2-weeks
2-months
SLTFarrajota 2012 [43]Intervention: nfvPPA: 2, svPPA: 2, lvPPA: 6 Control: nfvPPA: 0, svPPA: 6, lvPPA: 4Post-Treatment
Meyer 2019 [42]svPPA: 5,
lvPPA: 9, nfvPPA: 12		1-month
Rogalski 2022 [29]nfvPPA: 15, svPPA: 4, lvPPA: 18, other variants: 122-months
6-months
Errorless learning therapyJokel 2010 [66] svPPA: 1Post-Treatment
Jokel 2016 [49]svPPA: 4Post-Treatment
Themistocleous 2021 [55]nfvPPA with AOS: 8Post-Treatment
2-months
Cognitive and picture naming therapyJoubert 2023 [30]svPPA: 1Post-Treatment
6-months
Phonological and orthographic therapyMeyer 2015 [50]lvPPA: 11-week
8-months
1-year
20-months
3-years
Meyer 2016 [41]svPPA: 5, lvPPA: 91-month
Meyer 2019 [42]svPPA: 5,
lvPPA: 9, nfvPPA: 12		1-month
tDCS and cognitive therapy (ICAT)Cotelli 2014 [44]lvPPA: 162-weeks
12-weeks
Tsapkini 2014 [60]nfvPPA: 2, lvPPA: 4Post-Treatment
2-weeks
2-months
rTMS and language therapyPytel 2021 [35]nfvPPA: 16, svPPA: 4Post-Treatment
VISTA Henry 2018 [34] nfvPPA: 10Post-treatment
3-months
6-months
1-year
LRCGrasso 2019 [76]Mixed PPA: 1, Mild cognitive Impairment: 1Post-Treatment
3-months
6-months
Suárez-González 2015 [73]svPPA: 1Post-Treatment
Croot 2019 [79]nfvPPA: 3, lvPPA: 2, svPPA: 2, Mixed PPA: 1Post-Treatment
PPA: primary progressive aphasia; nfvPPA: nonfluent/agrammatic variant primary progressive aphasia; svPPA: svPPA: semantic variant primary progressive aphasia; lvPPA: logopenic variant of primary progressive aphasia; AOS: apraxia of speech; CILT: constraint-induced language therapy; COEN: cognitive and executive naming; HD-tDCS: high-definition transcranial direct current stimulation; hf-rTMS: high-frequency repetitive transcranial magnetic stimulation; ICAT: intensive comprehensive aphasia therapy; LeFT: lexical feature training; LRC: lexical retrieval cascade; RRIPP: repetitive rehabilitation for impaired phonological processing; rTMS: repetitive transcranial magnetic stimulation; SLT: speech-language therapy; tDCS: transcranial direct current stimulation; VISTA: video-implemented script training for aphasia.
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MDPI and ACS Style

Alrasheed, A.S.; Alshamrani, R.A.; Al Ameer, A.A.; Alkahtani, R.M.; AlMohish, N.M.; AlQarni, M.A.; Alabdali, M.M. Safety and Efficacy of Different Therapeutic Interventions for Primary Progressive Aphasia: A Systematic Review. J. Clin. Med. 2025, 14, 3063. https://doi.org/10.3390/jcm14093063

AMA Style

Alrasheed AS, Alshamrani RA, Al Ameer AA, Alkahtani RM, AlMohish NM, AlQarni MA, Alabdali MM. Safety and Efficacy of Different Therapeutic Interventions for Primary Progressive Aphasia: A Systematic Review. Journal of Clinical Medicine. 2025; 14(9):3063. https://doi.org/10.3390/jcm14093063

Chicago/Turabian Style

Alrasheed, Abdulrahim Saleh, Reem Ali Alshamrani, Abdullah Ali Al Ameer, Reham Mohammed Alkahtani, Noor Mohammad AlMohish, Mustafa Ahmed AlQarni, and Majed Mohammad Alabdali. 2025. "Safety and Efficacy of Different Therapeutic Interventions for Primary Progressive Aphasia: A Systematic Review" Journal of Clinical Medicine 14, no. 9: 3063. https://doi.org/10.3390/jcm14093063

APA Style

Alrasheed, A. S., Alshamrani, R. A., Al Ameer, A. A., Alkahtani, R. M., AlMohish, N. M., AlQarni, M. A., & Alabdali, M. M. (2025). Safety and Efficacy of Different Therapeutic Interventions for Primary Progressive Aphasia: A Systematic Review. Journal of Clinical Medicine, 14(9), 3063. https://doi.org/10.3390/jcm14093063

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