RARE DISEASE
Logopenic progressive aphasia
Logopenic progressive aphasia
Logopenic progressive aphasia
Synonyms: LPA, Logopenic primary progressive aphasia, Logopenic variant PPA
Synonyms: LPA, Logopenic primary progressive aphasia, Logopenic variant PPA
Synonyms: LPA, Logopenic primary progressive aphasia, Logopenic variant PPA
Drug discovery
0
drugs
With orphan designations
Overview
Logopenic progressive aphasia (LPA) is a language-predominant dementia characterized by impaired word retrieval, sentence repetition deficits, and phonological errors, often linked to Alzheimer’s disease pathology [1][5][16]. It arises from left posterior temporal/inferior parietal atrophy, progressing to broader cognitive decline, dependency, and behavioral symptoms like irritability or memory impairment [1][4][6]. Diagnosis relies on speech hesitations, preserved single-word comprehension, and exclusion of motor speech deficits [5][16].
Burden
Rapid decline in verbal communication, necessitating full-time care within 3–10 years [2][6][17].
High caregiver stress due to communication breakdowns and comorbid depression/motor impairments [6][15].
Survival parallels Alzheimer’s (~7–10 years post-diagnosis), with quality of life heavily impacted [2][16].
Therapies
Speech-language therapy: Intensive semantic training improves lexical retrieval; AAC devices support communication [3][8][18].
Pharmacotherapy: Off-label use of AD medications (e.g., acetylcholinesterase inhibitors) with limited efficacy [13][16].
Multidisciplinary care: Focus on caregiver education, environmental modifications, and behavioral symptom management [6][8][10].
Categories: rare neurological diseases
Research Papers
148 drug discovery papers about Logopenic progressive aphasia, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
148 drug discovery papers about Logopenic progressive aphasia, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2024-12-01 | Alzheimer’s disease as a primary pathology in logopenic variant of primary progressive aphasia
Abstract Background The logopenic variant of primary progressive aphasia (lvPPA) is a disorder centered on language impairment. Alzheimer Disease (AD) is one of the most common underlying pathologies in lvPPA. The aim of our study was to estimate frequency of AD in this phenotype and to analyze clinical features of AD‐lvPPA. Method We examined 20 patients (9 females and 11 males, 65.9±9.1 years) with the phenotype of lvPPA. The diagnosis was determined on clinical and imaging data according to the lvPPA criteria (Gorno‐Tempini et al., 2011). All patients underwent lumbar puncture. CSF biomarkers Abeta‐42 and p‐tau181 were analyzed. Based on the laboratory results and according to the recommendations of International Working Group (2021) we found 4 patients with established AD, 8 patients with probable AD and 8 non‐AD patients. Then we compared 2 groups (AD and non‐AD) on age of onset and cognitive features, assessed by Addenbrooke’s cognitive examination (ACE‐R) and Frontal Assessment Battery (FAB). Result The frequency of AD pathology in lvPPA group was 60% (20% for established diagnosis and 40% ‐ for probable). The disease onset was earlier in the group of AD lvPPA than in the non‐AD group (60.1 years vs. 65.4 years), but the difference was not statistically significant (p=0.175). We didn’t find significant differences between the groups in FAB, total ACE‐R. We revealed a higher median score in the speech ACE‐R subscale (18.5 vs. 14.5) and lower median score in the memory ACE‐R subscale (10.5 vs. 14.5) in patients with established AD group compared to non‐AD group. Conclusion In our study we demonstrated a high prevalence of AD pathology in lvPPA. The results showed no specific differences, but some clinical findings may predict AD on pre‐laboratory stage (such as more severe memory impairment and less speech impairment). So, it is important to analyze AD biomarkers in CSF in all cases to establish underlying pathology and to prescribe specific treatment. The study was supported by RSF (#23‐25‐00483)
2024-09-11 | Efficacy of Acetylcholinesterase Inhibitors in the Logopenic Variant of Primary Progressive Aphasia.
For over 25 years, cholinesterase inhibitors (ChEIs) have been the main symptomatic treatment for Alzheimer's disease (AD). Several meta-analyses have supported their effectiveness in various neurocognitive, functional, and behavioral aspects of amnestic AD. Over 86% of cases of the logopenic variant of primary progressive aphasia (lvPPA), also named language variant AD, are caused by a similar pathologic process than AD, yet no study has examined the efficacy of ChEIs in this AD variant. We aimed to explore the efficacy of ChEIs in the treatment of lvPPA by comparing their evolution on the MMSE, and other functional and behavioral parameters, to that of treated amnestic AD patients. A retrospective chart review was performed in 45 patients with lvPPA and 52 patients with amnestic AD. Both groups were similar in terms of age, level of education, and onset of symptoms. Drug history and MMSE scores, as well as functional (activities of daily living [ADLs] and instrumental activities of daily living [IADLs]), neurocognitive and neuropsychiatric symptoms were collected on several time points before and after the introduction of ChEIs. Data were analyzed using ANOVA and a generalized linear mixed model. Patients with lvPPA showed a similar trajectory of decline than amnestic AD patients on serial MMSEs up to 12-24 months after the introduction of ChEIs. There was a significant impact on ADLs but not IADLs and neuropsychiatric symptoms remained stable over time. This study provides preliminary evidence for efficacy of ChEIs in patients with lvPPA and suggests similar benefits to those seen in amnestic AD patients, hence reassuring patients and their physicians. For over 25 years, cholinesterase inhibitors (ChEIs) have been the main symptomatic treatment for Alzheimer's disease (AD). Several meta-analyses have supported their effectiveness in various neurocognitive, functional, and behavioral aspects of amnestic AD. Over 86% of cases of the logopenic variant of primary progressive aphasia (lvPPA), also named language variant AD, are caused by a similar pathologic process than AD, yet no study has examined the efficacy of ChEIs in this AD variant. We aimed to explore the efficacy of ChEIs in the treatment of lvPPA by comparing their evolution on the MMSE, and other functional and behavioral parameters, to that of treated amnestic AD patients. A retrospective chart review was performed in 45 patients with lvPPA and 52 patients with amnestic AD. Both groups were similar in terms of age, level of education, and onset of symptoms. Drug history and MMSE scores, as well as functional (activities of daily living [ADLs] and instrumental activities of daily living [IADLs]), neurocognitive and neuropsychiatric symptoms were collected on several time points before and after the introduction of ChEIs. Data were analyzed using ANOVA and a generalized linear mixed model. Patients with lvPPA showed a similar trajectory of decline than amnestic AD patients on serial MMSEs up to 12-24 months after the introduction of ChEIs. There was a significant impact on ADLs but not IADLs and neuropsychiatric symptoms remained stable over time. This study provides preliminary evidence for efficacy of ChEIs in patients with lvPPA and suggests similar benefits to those seen in amnestic AD patients, hence reassuring patients and their physicians.
2023-12-01 | Study on the effectiveness of acetylcholinesterase inhibitors in the treatment of primary progressive logopenic aphasia
Abstract Background For over 25 years, cholinesterase inhibitors (ChEIs) have been the main symptomatic treatment for Alzheimer’s disease (AD). Several meta‐analyses have supported their effectiveness in various neurocognitive aspects of amnestic AD. Over 86% of cases of the logopenic variant of primary progressive aphasia (lvPPA) are caused by a similar pathologic process than AD, yet no study has examined the efficacy of ChEIs in this AD variant. We aimed to explore the efficacy of ChEIs in the treatment of lvPPA by comparing their longitudinal MMSEs to that of treated amnestic AD patients. Method A retrospective chart review was performed on 48 patients with lvPPA and 52 patients with amnestic AD. Both groups were similar with respect to age, level of education, and onset of symptoms. Drug history and MMSE scores were collected on several time points before and after the introduction of ChEIs. Results Patients with lvPPA showed a similar trajectory of decline than amnestic AD patients on serial MMSEs (both WORLD and 100‐7) up to twelve months after the introduction of ChEIs (Figure 1 and 2). Conclusion This study provides preliminary evidence for efficacy of ChEIs in patients with lvPPA and suggests similar benefits to those seen in amnestic AD patients.
2021-10-03 | Differential chemokine alteration in the variants of primary progressive aphasia—a role for neuroinflammation
Abstract Background The primary progressive aphasias (PPA) represent a group of usually sporadic neurodegenerative disorders with three main variants: the nonfluent or agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). They are usually associated with a specific underlying pathology: nfvPPA with a primary tauopathy, svPPA with a TDP-43 proteinopathy, and lvPPA with underlying Alzheimer’s disease (AD). Little is known about their cause or pathophysiology, but prior studies in both AD and svPPA have suggested a role for neuroinflammation. In this study, we set out to investigate the role of chemokines across the PPA spectrum, with a primary focus on central changes in cerebrospinal fluid (CSF) Methods Thirty-six participants with sporadic PPA (11 svPPA, 13 nfvPPA, and 12 lvPPA) as well as 19 healthy controls were recruited to the study and donated CSF and plasma samples. All patients with lvPPA had a tau/Aβ42 biomarker profile consistent with AD, whilst this was normal in the other PPA groups and controls. We assessed twenty chemokines in CSF and plasma using Proximity Extension Assay technology: CCL2 (MCP-1), CCL3 (MIP-1a), CCL4 (MIP-1β), CCL7 (MCP-3), CCL8 (MCP-2), CCL11 (eotaxin), CCL13 (MCP-4), CCL19, CCL20, CCL23, CCL25, CCL28, CX3CL1 (fractalkine), CXCL1, CXCL5, CXCL6, CXCL8 (IL-8), CXCL9, CXCL10, and CXCL11. Results In CSF, CCL19 and CXCL6 were decreased in both svPPA and nfvPPA compared with controls whilst CXCL5 was decreased in the nfvPPA group with a borderline significant decrease in the svPPA group. In contrast, CCL2, CCL3 and CX3CL1 were increased in lvPPA compared with controls and nfvPPA (and greater than svPPA for CX3CL1). CXCL1 was also increased in lvPPA compared with nfvPPA but not the other groups. CX3CL1 was significantly correlated with CSF total tau concentrations in the controls and each of the PPA groups. Fewer significant differences were seen between groups in plasma, although in general, results were in the opposite direction to CSF, i.e. decreased in lvPPA compared with controls (CCL3 and CCL19), and increased in svPPA (CCL8) and nfvPPA (CCL13). Conclusion Differential alteration of chemokines across the PPA variants is seen in both CSF and plasma. Importantly, these results suggest a role for neuroinflammation in these poorly understood sporadic disorders, and therefore also a potential future therapeutic target.
2021-05-14 | Apathy and its impact on carer burden and psychological wellbeing in primary progressive aphasia.
While patients with primary progressive aphasia (PPA) typically present with predominant language impairment, behavioural symptoms, such as apathy, are often under-recognised. We aimed to systematically characterise apathy across the three recognised subtypes of PPA, plus atypical right-lateralised presentations of semantic dementia, and to evaluate the impact of apathy on carer burden and psychological wellbeing. Baseline assessments from 114 PPA patients were included: 31 left semantic dementia (left SD) 16 right semantic dementia (right SD), 30 progressive nonfluent aphasia (PNFA) and 37 logopenic progressive aphasia (LPA). Clinician (Neuropsychiatric Inventory; NPI) and carer rated (Cambridge Behavioural Inventory; CBI, Frontal Systems Behaviour Scale; FrSBe) measures were used to quantify symptoms of apathy, and carer burden and psychological wellbeing were determined using the Zarit Burden Interview and Depression, Anxiety and Stress Scale. On the NPI, symptoms of apathy were present in 39% left SD, 56% right SD, 33% PNFA and 43% LPA patients. Multiple regression analysis revealed that 17.9% of the variance in carer burden was uniquely explained by scores on carer rated measures of apathy (CBI, FrSBe), even after accounting for diagnosis, disease duration, and cognitive and language impairment. Apathy is much more common than current diagnostic criteria for PPA would suggest, though the severity of apathy is similar across patient groups. Increased awareness and routine assessments of apathy symptoms are needed, together with targeted pharmacological and behavioural interventions. Moreover, as apathy substantially contributes to carer burden in PPA, psychoeducation addressing behavioural symptoms may be beneficial.
oligonucleotides
2022-04-26 | Eyetracking during picture naming predicts future vocabulary dropout in progressive anomia.
The dynamic and unpredictable nature of expressive vocabulary dropout in progressive anomia presents a challenge for language intervention. We evaluated whether eye gaze patterns during naming could predict anomia for the same items in the near future. We tracked naming accuracy and gaze patterns as patients with semantic (n = 7) or logopenic (n = 2) variants of Primary Progressive Aphasia or amnestic Alzheimer's Disease (n = 1), named photographs of people and objects. Patients were tested three or more times spaced roughly evenly over an average duration of 19.1 months. Target words named accurately at baseline were retrospectively coded as either known (i.e., consistently named) or vulnerable (i.e., inaccurately or inconsistently named) based on naming accuracy over the study interval. We extracted gaze data corresponding to successful naming attempts and implemented logistic mixed effects models to determine whether common gaze measures could predict each word's naming status as known or vulnerable. More visual fixations and greater visual fixation dispersion predicted later anomia. These findings suggest that eye tracking may yield a biomarker of the robustness of particular target words to future expressive vocabulary dropout. We discuss the potential utility of this finding for optimizing treatment for progressive anomia.
gene therapies
2023-03-02 | Structural correlates of language processing in primary progressive aphasia
Abstract Understanding the relationships between brain structure and language behaviour in primary progressive aphasia provides crucial information about these diseases’ pathomechanisms. However, previous investigations have been limited from providing a statistically reliable view of broad language abilities by sample size, variant focus and task focus. In this study, the authors aimed to determine the relationship between brain structure and language behaviour in primary progressive aphasia, to determine the degree to which task-associated regions were atrophied across disease variants and to determine the degree to which task-related atrophy overlaps across disease variants. Participants were 118 primary progressive aphasia patients and 61 healthy, age-matched controls tested from 2011 to 2018 in the German Consortium for Frontotemporal Lobar Degeneration cohort. Diagnosis of primary progressive aphasia required progressive deterioration of mainly speech and language for ≥ 2 years, and variant was diagnosed by the criteria of Gorno-Tempini et al. (Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-1014). Twenty-one participants not fulfilling a specific subtype were classified as mixed-variant and excluded. Language tasks of interest included the Boston naming test, a German adaptation of the Repeat and Point task, phonemic and category fluency tasks and the reading/writing subtest of the Aachen Aphasia Test. Brain structure was measured by cortical thickness. We observed networks of language task-associated temporal, frontal and parietal cortex. Overlapping task-associated atrophy was observed in the left lateral, ventral and medial temporal lobes, middle and superior frontal gyri, supramarginal gyrus and insula. Some regions, primarily in the perisylvian region, were associated with language behaviour despite showing no significant atrophy. The results crucially extend less powerful studies associating brain and language measures in primary progressive aphasia. Cross-variant atrophy in task-associated regions suggests partially shared underlying deficits, whereas unique atrophy reinforces variant-specific deficits. Language task-related regions that are not obviously atrophied suggest regions of future network disruption and encourage understanding of task deficits beyond clearly atrophied cortex. These results may pave the way for new treatment approaches.
small molecules
2024-12-01 | Alzheimer’s disease as a primary pathology in logopenic variant of primary progressive aphasia
Abstract Background The logopenic variant of primary progressive aphasia (lvPPA) is a disorder centered on language impairment. Alzheimer Disease (AD) is one of the most common underlying pathologies in lvPPA. The aim of our study was to estimate frequency of AD in this phenotype and to analyze clinical features of AD‐lvPPA. Method We examined 20 patients (9 females and 11 males, 65.9±9.1 years) with the phenotype of lvPPA. The diagnosis was determined on clinical and imaging data according to the lvPPA criteria (Gorno‐Tempini et al., 2011). All patients underwent lumbar puncture. CSF biomarkers Abeta‐42 and p‐tau181 were analyzed. Based on the laboratory results and according to the recommendations of International Working Group (2021) we found 4 patients with established AD, 8 patients with probable AD and 8 non‐AD patients. Then we compared 2 groups (AD and non‐AD) on age of onset and cognitive features, assessed by Addenbrooke’s cognitive examination (ACE‐R) and Frontal Assessment Battery (FAB). Result The frequency of AD pathology in lvPPA group was 60% (20% for established diagnosis and 40% ‐ for probable). The disease onset was earlier in the group of AD lvPPA than in the non‐AD group (60.1 years vs. 65.4 years), but the difference was not statistically significant (p=0.175). We didn’t find significant differences between the groups in FAB, total ACE‐R. We revealed a higher median score in the speech ACE‐R subscale (18.5 vs. 14.5) and lower median score in the memory ACE‐R subscale (10.5 vs. 14.5) in patients with established AD group compared to non‐AD group. Conclusion In our study we demonstrated a high prevalence of AD pathology in lvPPA. The results showed no specific differences, but some clinical findings may predict AD on pre‐laboratory stage (such as more severe memory impairment and less speech impairment). So, it is important to analyze AD biomarkers in CSF in all cases to establish underlying pathology and to prescribe specific treatment. The study was supported by RSF (#23‐25‐00483)
2024-09-11 | Efficacy of Acetylcholinesterase Inhibitors in the Logopenic Variant of Primary Progressive Aphasia.
For over 25 years, cholinesterase inhibitors (ChEIs) have been the main symptomatic treatment for Alzheimer's disease (AD). Several meta-analyses have supported their effectiveness in various neurocognitive, functional, and behavioral aspects of amnestic AD. Over 86% of cases of the logopenic variant of primary progressive aphasia (lvPPA), also named language variant AD, are caused by a similar pathologic process than AD, yet no study has examined the efficacy of ChEIs in this AD variant. We aimed to explore the efficacy of ChEIs in the treatment of lvPPA by comparing their evolution on the MMSE, and other functional and behavioral parameters, to that of treated amnestic AD patients. A retrospective chart review was performed in 45 patients with lvPPA and 52 patients with amnestic AD. Both groups were similar in terms of age, level of education, and onset of symptoms. Drug history and MMSE scores, as well as functional (activities of daily living [ADLs] and instrumental activities of daily living [IADLs]), neurocognitive and neuropsychiatric symptoms were collected on several time points before and after the introduction of ChEIs. Data were analyzed using ANOVA and a generalized linear mixed model. Patients with lvPPA showed a similar trajectory of decline than amnestic AD patients on serial MMSEs up to 12-24 months after the introduction of ChEIs. There was a significant impact on ADLs but not IADLs and neuropsychiatric symptoms remained stable over time. This study provides preliminary evidence for efficacy of ChEIs in patients with lvPPA and suggests similar benefits to those seen in amnestic AD patients, hence reassuring patients and their physicians. For over 25 years, cholinesterase inhibitors (ChEIs) have been the main symptomatic treatment for Alzheimer's disease (AD). Several meta-analyses have supported their effectiveness in various neurocognitive, functional, and behavioral aspects of amnestic AD. Over 86% of cases of the logopenic variant of primary progressive aphasia (lvPPA), also named language variant AD, are caused by a similar pathologic process than AD, yet no study has examined the efficacy of ChEIs in this AD variant. We aimed to explore the efficacy of ChEIs in the treatment of lvPPA by comparing their evolution on the MMSE, and other functional and behavioral parameters, to that of treated amnestic AD patients. A retrospective chart review was performed in 45 patients with lvPPA and 52 patients with amnestic AD. Both groups were similar in terms of age, level of education, and onset of symptoms. Drug history and MMSE scores, as well as functional (activities of daily living [ADLs] and instrumental activities of daily living [IADLs]), neurocognitive and neuropsychiatric symptoms were collected on several time points before and after the introduction of ChEIs. Data were analyzed using ANOVA and a generalized linear mixed model. Patients with lvPPA showed a similar trajectory of decline than amnestic AD patients on serial MMSEs up to 12-24 months after the introduction of ChEIs. There was a significant impact on ADLs but not IADLs and neuropsychiatric symptoms remained stable over time. This study provides preliminary evidence for efficacy of ChEIs in patients with lvPPA and suggests similar benefits to those seen in amnestic AD patients, hence reassuring patients and their physicians.
2023-12-01 | Study on the effectiveness of acetylcholinesterase inhibitors in the treatment of primary progressive logopenic aphasia
Abstract Background For over 25 years, cholinesterase inhibitors (ChEIs) have been the main symptomatic treatment for Alzheimer’s disease (AD). Several meta‐analyses have supported their effectiveness in various neurocognitive aspects of amnestic AD. Over 86% of cases of the logopenic variant of primary progressive aphasia (lvPPA) are caused by a similar pathologic process than AD, yet no study has examined the efficacy of ChEIs in this AD variant. We aimed to explore the efficacy of ChEIs in the treatment of lvPPA by comparing their longitudinal MMSEs to that of treated amnestic AD patients. Method A retrospective chart review was performed on 48 patients with lvPPA and 52 patients with amnestic AD. Both groups were similar with respect to age, level of education, and onset of symptoms. Drug history and MMSE scores were collected on several time points before and after the introduction of ChEIs. Results Patients with lvPPA showed a similar trajectory of decline than amnestic AD patients on serial MMSEs (both WORLD and 100‐7) up to twelve months after the introduction of ChEIs (Figure 1 and 2). Conclusion This study provides preliminary evidence for efficacy of ChEIs in patients with lvPPA and suggests similar benefits to those seen in amnestic AD patients.
2021-10-03 | Differential chemokine alteration in the variants of primary progressive aphasia—a role for neuroinflammation
Abstract Background The primary progressive aphasias (PPA) represent a group of usually sporadic neurodegenerative disorders with three main variants: the nonfluent or agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). They are usually associated with a specific underlying pathology: nfvPPA with a primary tauopathy, svPPA with a TDP-43 proteinopathy, and lvPPA with underlying Alzheimer’s disease (AD). Little is known about their cause or pathophysiology, but prior studies in both AD and svPPA have suggested a role for neuroinflammation. In this study, we set out to investigate the role of chemokines across the PPA spectrum, with a primary focus on central changes in cerebrospinal fluid (CSF) Methods Thirty-six participants with sporadic PPA (11 svPPA, 13 nfvPPA, and 12 lvPPA) as well as 19 healthy controls were recruited to the study and donated CSF and plasma samples. All patients with lvPPA had a tau/Aβ42 biomarker profile consistent with AD, whilst this was normal in the other PPA groups and controls. We assessed twenty chemokines in CSF and plasma using Proximity Extension Assay technology: CCL2 (MCP-1), CCL3 (MIP-1a), CCL4 (MIP-1β), CCL7 (MCP-3), CCL8 (MCP-2), CCL11 (eotaxin), CCL13 (MCP-4), CCL19, CCL20, CCL23, CCL25, CCL28, CX3CL1 (fractalkine), CXCL1, CXCL5, CXCL6, CXCL8 (IL-8), CXCL9, CXCL10, and CXCL11. Results In CSF, CCL19 and CXCL6 were decreased in both svPPA and nfvPPA compared with controls whilst CXCL5 was decreased in the nfvPPA group with a borderline significant decrease in the svPPA group. In contrast, CCL2, CCL3 and CX3CL1 were increased in lvPPA compared with controls and nfvPPA (and greater than svPPA for CX3CL1). CXCL1 was also increased in lvPPA compared with nfvPPA but not the other groups. CX3CL1 was significantly correlated with CSF total tau concentrations in the controls and each of the PPA groups. Fewer significant differences were seen between groups in plasma, although in general, results were in the opposite direction to CSF, i.e. decreased in lvPPA compared with controls (CCL3 and CCL19), and increased in svPPA (CCL8) and nfvPPA (CCL13). Conclusion Differential alteration of chemokines across the PPA variants is seen in both CSF and plasma. Importantly, these results suggest a role for neuroinflammation in these poorly understood sporadic disorders, and therefore also a potential future therapeutic target.
2021-05-14 | Apathy and its impact on carer burden and psychological wellbeing in primary progressive aphasia.
While patients with primary progressive aphasia (PPA) typically present with predominant language impairment, behavioural symptoms, such as apathy, are often under-recognised. We aimed to systematically characterise apathy across the three recognised subtypes of PPA, plus atypical right-lateralised presentations of semantic dementia, and to evaluate the impact of apathy on carer burden and psychological wellbeing. Baseline assessments from 114 PPA patients were included: 31 left semantic dementia (left SD) 16 right semantic dementia (right SD), 30 progressive nonfluent aphasia (PNFA) and 37 logopenic progressive aphasia (LPA). Clinician (Neuropsychiatric Inventory; NPI) and carer rated (Cambridge Behavioural Inventory; CBI, Frontal Systems Behaviour Scale; FrSBe) measures were used to quantify symptoms of apathy, and carer burden and psychological wellbeing were determined using the Zarit Burden Interview and Depression, Anxiety and Stress Scale. On the NPI, symptoms of apathy were present in 39% left SD, 56% right SD, 33% PNFA and 43% LPA patients. Multiple regression analysis revealed that 17.9% of the variance in carer burden was uniquely explained by scores on carer rated measures of apathy (CBI, FrSBe), even after accounting for diagnosis, disease duration, and cognitive and language impairment. Apathy is much more common than current diagnostic criteria for PPA would suggest, though the severity of apathy is similar across patient groups. Increased awareness and routine assessments of apathy symptoms are needed, together with targeted pharmacological and behavioural interventions. Moreover, as apathy substantially contributes to carer burden in PPA, psychoeducation addressing behavioural symptoms may be beneficial.
oligonucleotides
2022-04-26 | Eyetracking during picture naming predicts future vocabulary dropout in progressive anomia.
The dynamic and unpredictable nature of expressive vocabulary dropout in progressive anomia presents a challenge for language intervention. We evaluated whether eye gaze patterns during naming could predict anomia for the same items in the near future. We tracked naming accuracy and gaze patterns as patients with semantic (n = 7) or logopenic (n = 2) variants of Primary Progressive Aphasia or amnestic Alzheimer's Disease (n = 1), named photographs of people and objects. Patients were tested three or more times spaced roughly evenly over an average duration of 19.1 months. Target words named accurately at baseline were retrospectively coded as either known (i.e., consistently named) or vulnerable (i.e., inaccurately or inconsistently named) based on naming accuracy over the study interval. We extracted gaze data corresponding to successful naming attempts and implemented logistic mixed effects models to determine whether common gaze measures could predict each word's naming status as known or vulnerable. More visual fixations and greater visual fixation dispersion predicted later anomia. These findings suggest that eye tracking may yield a biomarker of the robustness of particular target words to future expressive vocabulary dropout. We discuss the potential utility of this finding for optimizing treatment for progressive anomia.
gene therapies
2023-03-02 | Structural correlates of language processing in primary progressive aphasia
Abstract Understanding the relationships between brain structure and language behaviour in primary progressive aphasia provides crucial information about these diseases’ pathomechanisms. However, previous investigations have been limited from providing a statistically reliable view of broad language abilities by sample size, variant focus and task focus. In this study, the authors aimed to determine the relationship between brain structure and language behaviour in primary progressive aphasia, to determine the degree to which task-associated regions were atrophied across disease variants and to determine the degree to which task-related atrophy overlaps across disease variants. Participants were 118 primary progressive aphasia patients and 61 healthy, age-matched controls tested from 2011 to 2018 in the German Consortium for Frontotemporal Lobar Degeneration cohort. Diagnosis of primary progressive aphasia required progressive deterioration of mainly speech and language for ≥ 2 years, and variant was diagnosed by the criteria of Gorno-Tempini et al. (Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-1014). Twenty-one participants not fulfilling a specific subtype were classified as mixed-variant and excluded. Language tasks of interest included the Boston naming test, a German adaptation of the Repeat and Point task, phonemic and category fluency tasks and the reading/writing subtest of the Aachen Aphasia Test. Brain structure was measured by cortical thickness. We observed networks of language task-associated temporal, frontal and parietal cortex. Overlapping task-associated atrophy was observed in the left lateral, ventral and medial temporal lobes, middle and superior frontal gyri, supramarginal gyrus and insula. Some regions, primarily in the perisylvian region, were associated with language behaviour despite showing no significant atrophy. The results crucially extend less powerful studies associating brain and language measures in primary progressive aphasia. Cross-variant atrophy in task-associated regions suggests partially shared underlying deficits, whereas unique atrophy reinforces variant-specific deficits. Language task-related regions that are not obviously atrophied suggest regions of future network disruption and encourage understanding of task deficits beyond clearly atrophied cortex. These results may pave the way for new treatment approaches.
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