Logopenic Aphasia Research Articles

The dynamics of auditory working memory impairment in logopenic aphasia and Alzheimer’s disease

AbstractBackgroundImpaired auditory verbal working memory is a diagnostic hallmark and integral driver of the clinical phenotype in logopenic aphasia. However, the physiology of the working memory buffer in this syndrome is poorly characterised. Here we addressed the temporal dynamics of auditory verbal working memory in patients with logopenic aphasia and typical Alzheimer’s disease.MethodIn a cohort of patients with logopenic aphasia and typical Alzheimer’s disease and in healthy age‐matched controls, we assessed how temporal manipulations of standard auditory verbal working memory tasks (forward and reverse digit span and phrasal repetition) affected performance. We varied tempo of delivery and inter‐trial gap and performed a detailed analysis of error types. Participants also had pure tone audiometry to assess peripheral hearing function and a comprehensive general neuropsychological assessment.ResultCompared with healthy controls, patients with logopenic aphasia and Alzheimer’s disease showed increased sensitivity to temporal manipulation of auditory verbal working memory tasks and error profiles suggesting a dynamic physiological lesion of the working memory buffer. These effects were particularly marked in the logopenic group.ConclusionOur findings open a novel physiological window on working memory dynamics in Alzheimer’s disease syndromes. Further work is warranted to assess how this dynamic deficit impacts communication in patients’ daily lives, how it can best inform management interventions and its potential as a novel, rapid read‐out of neural function in the era of disease‐modifying therapies.

The speech‐to‐song illusion in frontotemporal dementia and Alzheimer’s disease

AbstractBackgroundPerceptual plasticity depends on dynamic, coordinated synaptic tuning across neural circuits and is therefore likely to be vulnerable to neurodegenerative pathologies. However, the nature and limits of perceptual plasticity in dementia are largely unknown. Here we addressed this issue using a dramatic instance of auditory perceptual plasticity ‐ the speech‐to‐song illusion discovered by Diana Deutsch (2011), whereby a spoken phrase is perceived as sung after a few repetitions.MethodWe studied patients representing all major syndromes of frontotemporal dementia (FTD) (N = 22) and Alzheimer’s disease (AD) (N = 25) versus healthy age‐matched controls (N = 21). We asked each participant whether they experienced the Deutsch illusion, and separately assessed their ability to discriminate spoken and sung phrases. In patients who reported experiencing the illusion, we verified this using a forced‐choice procedure.ResultThe Deutsch illusion was reported by 76% of healthy controls, and by 44.4% with progressive non‐fluent aphasia (PNFA), 42.9% of patients with semantic dementia (SD), 20% with typical AD, 20% with logopenic aphasia (LPA), and none with behavioural variant FTD (bvFTD). Mean scores for speech/song discrimination were as follows: healthy controls, 99%; SD, 97.6%; AD, 95%; LPA, 94.7%; PNFA, 94%; bvFTD, 87%. bvFTD performed significantly lower than healthy controls at discrimination.ConclusionPerception of the speech‐to‐song illusion is reduced in canonical FTD and AD syndromes compared with healthy older people and stratifies dementia syndromes disproportionately to any underlying perceptual deficit. The illusion presents an interesting new model for assessing perceptual plasticity in these diseases.

Sleep disturbance associated with temporal lobe degeneration in frontotemporal dementia

AbstractBackgroundSleep abnormalities are increasingly recognized as markers and potential drivers of neurodegenerative proteinopathies. However, the sleep phenotype of less common dementias remains poorly characterised. In particular, clinical experience suggests that patients with focal temporal lobe degeneration in the frontotemporal dementia spectrum can experience sometimes striking sleep disruption. We recently had the opportunity to corroborate this clinical impression in a small series of representative patients participating in a larger cohort study.MethodsTo date, we have studied seven patients and three healthy age‐matched controls. The patients’ diagnoses comprise behavioural variant frontotemporal dementia associated with focal right temporal lobe atrophy (n = 3), semantic dementia associated with focal left temporal lobe atrophy (n = 2), young onset Alzheimer’s disease and logopenic aphasia (each n = 1). No participant had a past history of a clinical sleep disorder. Detailed data on sleep patterns, adapted standard sleep questionnaires (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale), overnight oximetry and neuropsychological test scores (covering domains of executive function, emotion processing, memory, and auditory perceptual learning) pre‐/post‐overnight sleep were collected with the assistance of patients’ caregivers.ResultsTwo patients with right temporal lobe atrophy and one with left temporal lobe atrophy had marked sleep fragmentation, in one right temporal case accompanied by frequent sleep attacks, with increased overall time in bed and/or attempting to sleep. Epworth and Pittsburgh indices in these patients indicated significant daytime sleepiness and reduced sleep quality; none had evidence of significant sleep apnoea on overnight oximetry. Comparatively mild clinical sleep disturbances were reported in patients with other dementia diagnoses. However, there was evidence for reduced auditory perceptual learning benefit from overnight sleep relative to healthy older controls, particularly in the patients with underlying Alzheimer pathology.ConclusionsThese preliminary findings suggest that focal temporal lobe degeneration may be associated with clinically relevant sleep disruption, as part of the more pervasive derangement of homeostasis in these syndromes. Further work is indicated to define the hypnic phenotype in detail, with sleep electrophysiology and correlative behavioural, neuroimaging and laboratory data in larger patient cohorts.

Ethnic Disparities in Clinical Presentation of Patients with Early‐Onset Alzheimer’s Disease

AbstractBackgroundEarly‐onset Alzheimer’s Disease (EOAD) affects patients under age 65 and may present with non‐amnestic features. Black patients are half as likely as White patients to be diagnosed despite twice as many risk factors. Ethnic disparities in EOAD have not been fully characterized.MethodsWe retrospectively collected data on ethnicity, level of education, Montreal Cognitive Assessment (MoCA) scores on EOAD patients diagnosed between 2017 and 2022 at The University of Chicago Memory Center.ResultsOf 88 total patients, 60 (68.8%) identified as White and 28 (31.8%) identified as Black. Age at diagnosis was 57.3 ± 5.24 years in Black patients compared to 55.9 ± 5.69 years In White patients. Average time to diagnosis was longer in Black patients (5 ± 9.21 yrs.) vs White patients (3.5 ± 6.44 yrs). Black patients had lower MoCA scores than Whites at presentation (12.17 ± 6.91 vs 15.15 ± 5.92), despite similar education levels among Black vs. White patients (14.71 ± 2.30 vs 15.21 ± 3.00).Black patients more commonly displayed an amnestic profile (19 or 67.9%) than a non‐amnestic presentation (9 or 32.1%), although 2 patients (7.14%) presented with visual symptoms suggestive of posterior cortical atrophy (PCA), 5 (17.9%) patients had prominent language symptoms suggestive of logopenic primary progress aphasia (l‐PPA) and 1 (3.6%) patient had an executive presentation, suggestive of executive variant of AD (EAD). In White patients, 11 (18.3%) were diagnosed with PCA, 10 (16.7%) with EAD and 8 (13.3%) with l‐PPA.Differences were noted in the application of diagnostic tests, in that neuropsychological testing (NPT) and CSF testing were less often ordered in Black patients (NPT: 8 (29%) in Blacks vs 45 (75%) Whites, p = 0.001; CSF: 4 (14%) Blacks vs 30 (50%) Whites, p = 0.002).ConclusionIn our cohort, Black patients with EOAD were on average older, more advanced, and experience longer delays and differences in diagnostic management than their White counterparts. Further work is needed to characterize the barriers to diagnosis for Black patients with EOAD and the potential differences in clinical presentations.

Study on the effectiveness of acetylcholinesterase inhibitors in the treatment of primary progressive logopenic aphasia

AbstractBackgroundFor 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.MethodA 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.ResultsPatients 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).ConclusionThis study provides preliminary evidence for efficacy of ChEIs in patients with lvPPA and suggests similar benefits to those seen in amnestic AD patients.

Ethnic Disparities in Clinical Presentation of Patients with Early-Onset Alzheimer’s Disease (P14-6.002)

<h3>Objective:</h3> N/A <h3>Background:</h3> Early-onset Alzheimer’s Disease (EOAD) affects patients younger than age 65 and may present with non-amnestic features. Black patients are half as likely to be diagnosed despite twice as many risk factors. Ethnic disparities in EOAD have not been fully characterized. <h3>Design/Methods:</h3> We retrospectively identified EOAD patients February 2017–February 2022 and collected data on ethnicity, level of education, Montreal Cognitive Assessment (MoCA) scores and clinical presentation. <h3>Results:</h3> Of 88 total patients, 60 (68.8%) identified as Caucasian/White and 28 (31.8%) identified as African American/Black. Age at diagnosis (years) was (57.3 ± 5.24) in Black patients compared to (55.9 ± 5.69) in White patients. Time to diagnosis (years) was on average longer in Black patients (5 ± 9.21) compared with White patients (3.5 ± 6.44) and Black patients were on average more advanced (total MOCA scores) at presentation (12.17 ± 6.91) compared with White patients (15.15 ± 5.92) despite similar education level (in years) among Black patients (14.71 ± 2.30) and White patients (15.21±3.00). An amnestic profile was more common in Black patients (19 or 67.9%) than non-amnestic presentations (9 or 32.1%), although 2 patients (7.14%) presented with visual symptoms suggestive of posterior cortical atrophy (PCA), 5 (17.9%) patients had prominent language symptoms suggestive of logopenic primary progress aphasia (l-PPA) and 1 (3.6%) patient had an executive presentation, suggestive of frontal variant of AD (fAD). Comparatively, non-amnestic presentations were more commonly diagnosed in White patients, with 11 (18.3%) PCA diagnoses, 10 (16.7%) patients with fAD and 8 (13.3%) patients with l-PPA. <h3>Conclusions:</h3> In our cohort, Black patients with EOAD are on average older, more advanced and experience longer delays in diagnosis than their White counterparts. Non-amnestic presentations are more common in White patients. Further work is needed to further characterize the barriers to diagnosis accessibility of care for Black patients with EOAD. <b>Disclosure:</b> Ms. Yang has nothing to disclose. Dr. Yoon has nothing to disclose. Ms. Covaciu has nothing to disclose. The institution of Dr. Seibert has received research support from Retirement Research Foundation. The institution of Dr. Seibert has received research support from Center for Healthcare Delivery Science and Innovation.

Supporting spiritual health in dementia using the WELLHEAD Toolkit: A ‘story-tale’ from a person with logopenic aphasia

ABSTRACT Little is known about the spirituality of people with logopenic aphasia (language-led dementia), including assessment and support. This article presents a single case study from a case series of ten people with various aphasia-types and different religious backgrounds who were recruited after discharge from speech and language therapy (SLT). Based on work with ‘Mr Grey’, it illustrates the use of the ‘WELLHEAD Toolkit’ for assessing and supporting spiritual health. A group of people with aphasia and diverse backgrounds co-produced the resources and steered the research. The Toolkit provides communication support and structure for eliciting interviews about ‘meaning and purpose’ in life. It enables religiously neutral non-judgmental listening and facilitates reflection using Picture and Word Resources, incorporating self-scores, an agreed summary, and goal-setting. Sessions were videoed along with a feedback interview. Participants’ reflections, measures, and verification were integral to the findings from the case series. Findings were analysed via systematic interpretive thematic analysis, verified by an independent researcher. Key themes in Mr Grey’s case are presented in narrative form to respect his own words, interpreted and verified for meaning, within his search for synthesis of his fragmented story. His story-telling brought him catharsis concerning relationships, religious beliefs and sense of self, whilst helping him to frame future goals. Follow-up confirmed the value of enabling chaplaincy referral as a result of the interviews. This helped him towards resolving historical grief before further language deterioration. Limitations and potential future applications of the WELLHEAD Toolkit are discussed.

CSF Alzheimer’s biomarkers in clinical practice

AbstractBackgroundCSF biomarkers are well validated and a useful tool for the diagnosis of Alzheimer’s disease (AD). However, in some cases results are not consistent. In this study we examine to which extent CSF biomarkers support diagnosis in clinical practice.MethodAnalysis of 141 consecutive CSF samples of patients referred to our memory clinic with suspected cognitive decline, using the Lumipulse G600II chemiluminescent immunoassay (Fujirebio, Spain) to determine Ab‐42/Ab‐40 ratio (A+ if &lt;0.068), total Tau (N+ if &gt;410 pg/ml), and phospho‐Tau (T+ if &gt;59 pg/ml).Clinical diagnosis was classified into three categories: AD, degenerative non‐AD, and non degenerative, considering current clinical criteria at last visit.Based on biomarkers, we separated the groups as follows: negative for AD (A‐T‐N‐ and A‐T‐N+), positive for AD (A+T+N+ and A+T+N‐), cases with amyloidosis A+ but T‐ (A+T‐N+; A+T‐N‐), and cases without amyloidosis A‐ but T+ (A‐T+N+).Result50,5% of the patients had a positive AD result that correlated in a majority of cases with a clinical amnestic AD phenotype or other highly related phenotypes (logopenic aphasia and posterior cortical atrophy). The exceptions were 5 cases meeting diagnostic criteria for non‐fluent/agrammatic aphasia or corticobasal syndrome.37% had a negative AD result which correlated with a clinical diagnosis of non‐AD neurodegeneration (25 cases) or non degenerative (27 cases).Therefore, in 87% of the cases CSF biomarkers supported a clinical diagnosis.On the other hand, 18 cases (13%) had some inconsistencies within biomarkers: 7 with A‐ and 11 with A+ results. As regards clinical diagnosis, all A‐T+N+ and many of the patients with A+ biomarkers (8/11) had been considered AD phenotypes. In two of the cases with A+T‐N‐, an AD diagnosis was later confirmed, respectively, by a positive PET‐amyloid study and full positive CSF biomarkers analyzed two years later.No differences were found in family history, age of onset, or age at lumbar puncture between the groups of AD positive biomarkers and just amyloidosis A+.ConclusionCSF biomarkers were clearly supportive of the clinical diagnosis in a majority of the cases of our cohort. However, in 13% of the cases, most of them with an AD type phenotype, biomarkers were unclear.

Remote versus face-to-face neuropsychological testing for dementia research: a comparative study in people with Alzheimer’s disease, frontotemporal dementia and healthy older individuals

ObjectivesWe explored whether adapting neuropsychological tests for online administration during the COVID-19 pandemic was feasible for dementia research.DesignWe used a longitudinal design for healthy controls, who completed face-to-face assessments 3–4...

Relationship of APOE, age, amyloid and clinical phenotype in Alzheimer disease

AbstractBackgroundThe apolipoprotein ε4 (APOE4) allele is the most common and well established risk factor for typical late‐onset amnestic Alzheimer’s dementia. Less is known about the role of APOE in patients with atypical clinical presentations of AD, with studies often disagreeing on APOE4 frequencies in these cohorts. We aimed to assess relationships between APOE genotype and age, amyloid‐beta (Aβ) deposition and clinical phenotype in Alzheimer’s disease.Method138 atypical AD patients (57 posterior cortical atrophy and 81 logopenic aphasia) were recruited by the Neurodegenerative Research Group at Mayo Clinic, and underwent APOE testing and Pittsburgh Compound B PET. 318 typical AD patients with APOE genotype and known onset age were identified from ADNI (121 had Aβ‐PET). Aβ‐PET was quantified using the centiloid scale. Logistic regression was used to estimate the proportion of APOE4 carriers by onset age and clinical group. Linear regression was used to estimate mean Aβ centiloid by age, APOE4 status, and clinical group in patients who were Aβ‐positive (centiloid≥19).ResultThe overall frequency of APOE4 carriers was lower in atypical AD (52%) compared to typical AD (66%), particularly for ε4ε4 homozygotes (9% vs 20%). APOE4 frequency increased with age in atypical AD, but showed a bell‐shaped curve in typical AD where highest frequencies were observed between 65‐70 years (Figure). Typical AD showed higher APOE4 frequencies than atypical AD only between the ages of 57 and 69 years. Aβ centiloid was higher in atypical AD compared to typical AD by approximately 16 centiloid units, but did not differ according to APOE4 status (Figure). Aβ centiloid stayed relatively flat with increasing age for both carriers and non‐carriers in atypical AD, but declines with increasing age in typical AD. Relationships between APOE4 and age, as well as centiloid, did not differ between the two atypical AD phenotypes.ConclusionAPOE4 frequency differs between atypical and typical AD but is highly dependent upon age, with higher APOE4 frequency in typical AD only observed between 57 and 69 years. The findings highlight the importance of age and clinical phenotype in understanding the effects of APOE genotype in Alzheimer’s disease.

The linguistic impairment of the perfect aspect in Alzheimer’s disease and logopenic primary progressive aphasia

Taking into account that neuropsychological studies with subjects with language pathologies can contribute to the investigation of the organization of syntactic knowledge, the objective of this work is to investigate the syntactic representation of the perfect aspect based on data from subjects with pathologies that affect their language. More specifically, we aimed to investigate the possible phrases associated with the types of the perfect aspect and the hierarchy among them. This work aims to investigate the syntactic representation of the perfect aspect. Therefore, we sought to verify a possible linguistic impairment of this aspect in individuals diagnosed with Alzheimer's Disease (AD) and Primary Progressive Logopenic Aphasia (LPPA). A double case study was carried out with one patient with AD and another with LPPA. The methodology consisted of applying functionality tests, neuropsychological tests, and linguistic tests. The results indicated that both the AD patient and the LPPA patient present functional decline and cognitive impairment, with the degree of impairment of the first patient being more extensive than that of the second one in both cases. Regarding language, the patient with AD showed impairment with all four types of perfect, present tense, and imperfective aspect, whereas the LPPA patient has shown impairment only in perfect of recent past and present tense. Based on the results we propose the existence of a phrase to perfect of recent past and the dominance of the temporal phrase over the perfect phrases in the syntactic hierarchy.

A systematic review of atypical Alzheimer's disease including behavioural and psychological symptoms.

Alzheimer's disease (AD) is the commonest cause of dementia, characterized by the clinical presentation of progressive anterograde episodic memory impairment. However, atypical presentation of patients is increasingly recognized. These atypical AD include logopenic aphasia, behavioural variant AD, posterior cortical atrophy, and corticobasal syndrome. These atypical AD are more common in patients with young onset AD before the age of 65 years old. Since medical needs (including the behavioural and psychological symptoms of dementia) of atypical AD patients could be different from typical AD patients, it is important for clinicians to be aware of these atypical forms of AD. In addition, disease modifying treatment may be available in the future. This review aims at providing an update on various important subtypes of atypical AD including behavioural and psychological symptoms.

A longitudinal study of automated analysis of acoustic speech markers in FTD and PPA

AbstractBackgroundSpeech is a complex activity requiring proper function and connectivity of multiple brain networks and as such is sensitive to focal neurodegeneration. We have previously reported on acoustic markers of dysprosody in speech samples of speakers with frontotemporal dementia (FTD) phenotypes. In the current study we explore the longitudinal changes in acoustic‐prosodic markers in FTD.MethodWe analyzed 102 speech samples of picture descriptions from 46 participants with FTD (Table 1): 8 with non‐fluent/agrammatic primary progressive aphasia (naPPA), 14 with semantic variant PPA (svPPA), 10 with logopenic aphasia (lvPPA) and 14 with behavioral FTD (bvFTD). We automatically segmented the acoustic signal into segments of continuous speech or silence, measured their durations, and derived other measures. We used linear mixed effects (lme) models to test changes over time for each acoustic measure, controlling for sex, education, and random intercepts. We also examined any interaction between phenotypes and disease duration.ResultbvFTD speakers increased their pause duration by 0.27 seconds per year and their pause rate by 3.9 pauses per minute (ppm) each year. Their speech segment duration shortened by 0.1 seconds per year (p=0.041), decreasing their total speech time by 6.6 seconds (p=0.003) per year. Thus, bvFTD patients reduced the proportion of speech in their samples by 5.16 percent per year (p=0.008). svPPA speakers increased their pause rate similarly, but in contrast, their pause duration decreased by 0.097 seconds per year and they increased their speech segment frequency by 8.32 per minute each year (p=0.054). naPPA and lvPPA speakers increased their pause rate over time and spent less total time (speech + pause) describing the picture (by 5.6 seconds per year; p=0.018). They did not differ from bvFTD and svPPA in these two acoustic measures.ConclusionIn our study all FTD speakers became more dysfluent and produced shorter descriptions with time, however, only bvFTD speakers actually exhibited reduced speech production. In contrast, svPPA speech had more frequent pauses and speech segments over time, rendering it “fragmented” and inefficient. These findings support the role of automated acoustic analysis in characterizing speech longitudinally in neurodegeneration.

Occupational burnout‐like syndrome in early‐onset Alzheimer’s disease

AbstractBackgroundEarly‐onset Alzheimer’s disease (EOAD) differentiates from late‐onset AD by a predominant and early involvement of the parietal neocortex with hippocampal sparing, leading to non‐amnesic cognitive syndromes (deficits in working memory, visuospatial abilities, praxis, or language). The diagnosis of a neurodegenerative disease is often not the first mentioned in such young patients. We aimed to identify the inaugural symptoms and diagnosis in working age EOAD patients.MethodsWe retrospectively reviewed the files of patients younger than 62 years referred to our memory clinic for cognitive dysfunction during the last year. Among 91 patients, 31 were diagnosed with AD based on clinical and biological criteria (cerebrospinal fluid biomarkers). Their mean age was 55±3.8 years.ResultsEleven EOAD patients (35%) were initially diagnosed with an occupational burnout syndrome, while logopenic aphasia or visuo‐spatial deficit were observed in the remaining 20 patients (65%). In the burnout syndrome subgroup, the delay between the first symptoms and neurological examination was 2.6±1.1 years. The initial Mini‐Mental State Examination score was 19.6±4.6/30. Neuropsychological assessment showed a severe working memory deficit, associated with mild cognitive cortical parietal syndrome. Visual inspection of brain MRI and FDG‐PET showed bilateral parietal atrophy and a severe focal hypometabolism of associative parietal cortices. No patient had family history of EAOD and the molecular genetic testing of AD mutation was negative.ConclusionWe describe, for the first time, a new clinical presentation of EOAD mimicking an occupational burnout syndrome. The severe inaugural working memory deficit due to the early cortical parietal damage leads to an inability to carry out concurrent professional tasks, a reduction of professional efficacy and a severe anxiety, in the absence of overt aphasia or episodic memory deficit at the time of initial evaluation. The patient stops working and is often referred to psychiatrists, the diagnosis being delayed until the cognitive deficit worsens, and strongly affects the autonomy at a more advanced stage of the disease. It is crucial to consider this clinical phenotype in the definition of EOAD to avoid delayed diagnosis.

The Behavioral/Dysexecutive Variant of Alzheimer’s Disease: A Case Series with Clinical, Neuropsychological, and FDG-PET Characterization

Introduction: It is well known that some patients with Alz­heimer’s disease (AD) have atypical, nonamnestic presentations. While logopenic aphasia and posterior cortical atrophy are well-characterized atypical variants of AD, the behavioral/dysexecutive variant remains a controversial entity, lacking consensus regarding its distinctive clinical and imaging features. Methods: We present a case series of 8 patients with biomarker confirmation of AD (cerebrospinal fluid [CSF] analysis or amyloid positron emission tomography [PET]) and a progressive frontal syndrome, defined as prominent behavioral and/or executive deficits at initial presentation. We characterize the cohort based on clinical features, cognitive performance in 4 domains (memory, visuospatial, executive, and language) as well as behavior on the Dépistage Cognitif de Québec (DCQ), and regional brain metabolism using ¹⁸F-fluorodeoxyglucose PET (FDG-PET). We compare these features with 8 age-matched patients diagnosed with the behavioral variant of frontotemporal dementia (bvFTD) and 37 patients with typical amnestic AD. Results: Patients with the behavioral/dysexecutive variant of AD presented with early-onset (mean age: 59 years old) progressive executive and behavioral problems reminiscent of bvFTD, including disinhibition, loss of social conventions, and hyperorality. Patients scored higher on the Memory Index and lower on the Behavioral Index than patients with amnestic AD on the DCQ, yet they were indistinguishable from patients with bvFTD on each of the cognitive indices. Visual analysis of FDG-PET revealed half of patients with behavioral/dysexecutive AD presented with frontal hypometabolism suggestive of bvFTD and only 3/8 (37.5%) presented significant hypometabolism of the posterior cingulate cortex. Group-level analysis of FDG-PET data revealed that the most hypometabolic regions were the middle temporal, inferior temporal, and angular gyri in behavioral/dysexecutive AD and the inferior frontal gyrus, anterior cingulate cortex, caudate nucleus, and insula in bvFTD. Conclusion: The behavioral/dysexecutive variant of AD is a rare, atypical young-onset variant of AD defined clinically by early and prominent impairments in executive and behavioral domains. While behavioral/dysexecutive AD is hardly distinguishable from bvFTD using clinical and cognitive features alone, CSF biomarkers and temporoparietal hypometabolism help predict underlying pathology during life.

Altered Time Awareness in Dementia.

Our awareness of time, specifically of longer intervals spanning hours, days, months, and years, is critical for ensuring our sense of self-continuity. Disrupted time awareness over such intervals is a clinical feature in a number of frontotemporal dementia syndromes and Alzheimer's disease, but has not been studied and compared systematically in these diseases. We used a semi-structured caregiver survey to capture time-related behavioral alterations in 71 patients representing all major sporadic and genetic syndromes of frontotemporal dementia, in comparison to 28 patients with typical Alzheimer's disease and nine with logopenic aphasia, and 32 healthy older individuals. Survey items pertained to apparent difficulties ordering past personal events or estimating time intervals between events, temporal rigidity and clockwatching, and propensity to relive past events. We used a logistic regression model including diagnosis, age, gender, and disease severity as regressors to compare the proportions of individuals exhibiting each temporal awareness symptom between diagnostic groups. Gray matter associations of altered time awareness were assessed using voxel-based morphometry. All patient groups were significantly more prone to exhibit temporal awareness symptoms than healthy older individuals. Clinical syndromic signatures were identified. While patients with typical and logopenic Alzheimer's disease most frequently exhibited disturbed event ordering or interval estimation, patients with semantic dementia were most prone to temporal rigidity and clockwatching and those with behavioral variant frontotemporal dementia commonly exhibited all these temporal symptoms as well as a propensity to relive past events. On voxel-based morphometry, the tendency to relive past events was associated with relative preservation of a distributed left-sided temporo-parietal gray matter network including hippocampus. These findings reveal a rich and complex picture of disturbed temporal awareness in major dementia syndromes, with stratification of frontotemporal dementia syndromes from Alzheimer's disease. This is the first study to assess symptoms of altered temporal awareness across frontotemporal dementia syndromes and provides a motivation for future work directed to the development of validated clinical questionnaires, analysis of underlying neurobiological mechanisms and design of interventions.

The Landscape Montage Technique for diagnosing frontotemporal dementia starting as primary progressive aphasia: a case report

BackgroundThe Landscape Montage Technique was originally developed by Hisao Nakai, a Japanese psychiatrist, to pursue the possibility and application of a psychotherapeutic approach using drawing for patients with schizophrenia. Drawing was initially adopted to evaluate patients with an impaired ability for verbal expression, particularly for the diagnosis and treatment of patients with schizophrenia. Since its development, the Landscape Montage Technique has been utilized in various clinical settings throughout Japan. This study aimed to evaluate the psychiatric conditions of a patient diagnosed as having primary progressive aphasia using the Landscape Montage Technique at a 3-year follow-up.Case presentationWe present the case of a 64-year-old, right-handed Japanese woman initially diagnosed as having logopenic variant primary progressive aphasia or logopenic aphasia. At a 3-year follow-up, logopenic aphasia progressed to behavioral variant frontotemporal dementia or frontotemporal dementia. According to her husband, she began to have speech difficulties approximately 5 years before her first visit. The results of neurocognitive tests suggested mild cognitive impairment or early stages of dementia. Her clinical dementia rating score was 0.5, suggesting a diagnosis of mild cognitive impairment. She had a Raven’s Colored Progressive Matrices score of 31 out of 36, which indicated a nonverbal cognitive ability that was greater than the 90th percentile for her age. The Japanese Standard Language Test of Aphasia, which was performed at two points during the follow-up, indicated the possibility for a diagnosis of primary progressive aphasia given the progression of her aphasia. Based on her clinical symptoms and Japanese Standard Language Test of Aphasia results, a diagnosis of logopenic variant primary progressive aphasia was established. Magnetic resonance imaging revealed severe predominant left frontal and anterior temporal atrophy, as well as bilateral parietal atrophy. Amyloid beta deposition was negative. At the 3-year follow-up, logopenic variant primary progressive aphasia had progressed to behavioral variant frontotemporal dementia. However, the Landscape Montage Technique allowed for the diagnosis of behavioral variant frontotemporal dementia only 2 years after baseline.ConclusionsThe present study showed that the Landscape Montage Technique can be useful for diagnosing behavioral variant frontotemporal dementia that starts as logopenic variant primary progressive aphasia at earlier stages.

Diffusion fiber tractography on phonological loop with Logopenic aphasia tau pathology: Fiber-specific white matter reductions in Alzheimer's disease, “is it a causal or casual link?”

Introduction Logopenic Aphasia (LA), a variant of primary progressive aphasia characterized with difficulty in retrieving precise words, names, or numbers and sentence repetition. Previous studies detailed that 50% of LA patients had (Alzheimer's disease) AD pathology, and characteristics of LA synchronize with language impairments in AD. Researchers believed that, the atrophy of Phonological loop (A sensorimotor circuit that includes auditory regions, the inferior parietal lobe, and Broca's area, which integrates phonological processing and executes motor output) cause LA. Methodology We focused on structural connectivity of Phonological loop using ;“Diffusion Imaging fiber Tractography;” with 60 DTI datasets (30 Males and 30 Females) of both control and progressive stages of Alzheimer's, with the age range 55–120 years, with IRB approval and made an attempt to correlate the Logopenic aphasia, with phonological loop fiber-specific white matter reductions in early AD. Results Overall progressive diminution was observed in the phonological loop of males (Figs 1 & 2) and left hemispheric deterioration is markedly seen in terms of both fibers and tract volume (significant at p

Progression of logopenic aphasia to frontotemporal dementia in an amyloid β‐negative and 18F‐THK‐5351‐positive patient

Progression of logopenic aphasia to frontotemporal dementia in an amyloid β‐negative and ¹⁸F‐THK‐5351‐positive patient

Adaptation and validation of the Cantonese Sydney Language Battery for assessment of language deficits in patients with primary progressive aphasia in Hong Kong

Adaptation and validation of the Cantonese Sydney Language Battery for assessment of language deficits in patients with primary progressive aphasia in Hong Kong