John papatriantafyllou - Academia.edu (original) (raw)

Papers by John papatriantafyllou

Neuroimmunology and neuroinflammation, Jul 12, 2020

The classical cerebrospinal fluid biomarkers of Alzheimer's Disease (namely total tau, phospho-ta... more The classical cerebrospinal fluid biomarkers of Alzheimer's Disease (namely total tau, phospho-tau and amyloid beta peptide) have received much attention, since they can detect the biochemical fingerprint of Alzheimer's disease and serve as a diagnostic aid for correct diagnosis of cognitive disorders during life. In this case series, we present 6 examples of patients with cognitive impairment of various types and severities and how biomarker data were helpful in every day diagnostic approach, combined with clinical, neuropsychological and imaging data and based on the most recent guidelines and recommendations.

Behavioural Brain Research, Jul 1, 2020

Present review aimed to conduct a comprehensive review of the effectiveness of non-pharmacologica... more Present review aimed to conduct a comprehensive review of the effectiveness of non-pharmacological interventions (NPIs) on reducing anxiety in adult burn patients. Method: We searched PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases through September 2019 for randomized clinical trials comparing NPIs to a control group. The primary outcomes were general anxiety and pain anxiety. The Cochrane Risk of Bias Tool was used to assess the risk of bias. All data was pooled with Revman 5.3. Results: 20 studies were eligible for quantitative synthesis. Compared to routine care, Music (4 Randomized Clinical Trials (RCTs), Standardized Mean Difference (SMD) =-2.00, 95 % Confidence Interval (CI) =-3.21 to-0.79), massage (4 RCTs, SMD=-1.84, 95 % CI=-2.77 to-0.91), hypnosis (2 RCTs, SMD= −1.06, 95 % CI= −2.90 to 0.78), relaxation (2 RCTs, SMD= −0.77, 95 %CI= −1.52 to −0.02), transcranial direct current stimulation (1 RCT, SMD= −1.92, 95 %CI= −2.54 to −1.30), and therapeutic touch practices (1 RCT, SMD=−0.45 95 %CI= −0.86 to −0.04), were associated with a significant effect on the anxiety of burn patients. Aromatherapy interventions and virtual reality showed no evidence of a reduction in the anxiety. A large amount of heterogeneity exist among trials. Risk of bias varied across studies. Only one study reported on safety issues. Conclusion: Due to weak evidence, we are unable to make strong recommendations in favor of NPIs for burn anxiety. Further well-designed large sample size randomized clinical trials are warranted.

Frontiers in Communication, 2018

There is a growing body of research on language impairment in bilingual speakers with neurodegene... more There is a growing body of research on language impairment in bilingual speakers with neurodegenerative diseases. Evidence as to which language is better preserved is rather inconclusive. Various factors seem to influence language performance, most notably age of acquisition, level of proficiency, immersion and degree of exposure to each language. The present study examined fluency, lexical, discourse and grammatical abilities of a Greek-French late bilingual man with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA). Speech samples derived from three different narrative tasks in both languages were analyzed using quantitative production analysis (QPA) and fluency measures. The first aim of the study was to compare the participant's connected speech production to that of Greek-speaking normal controls. The second aim was to determine whether Greek (L1) and French (L2) were differentially impaired. To our knowledge, this is the first report of connected speech deficits in a Greek-speaking patient with PPA and the first study which uses QPA to compare L1 and L2 narratives in a bilingual speaker with PPA. Compared to neurologically healthy controls, our participant was impaired in lexical, discourse and grammatical productivity measures, but did not differ in measures of grammatical accuracy. The presence of dysfluencies, reduced speech rate and simplified syntax is consistent with the pattern of impairment reported for the nfvPPA. Results showed that narrative production measures did not differ significantly between languages. However, they suggest a slightly worse performance in his second, non-dominant, language despite a similar pattern of impairment in both languages. Lengthy exposure to L2 and regular activation of L2 through daily use may explain the preservation of discourse abilities in his non-dominant language. This study calls attention to factors such as language dominance, proficiency, patterns of use, and exposure to a language. These factors play a key role in assessing bilingual individuals with PPA and making clinical decisions.

Journal of Neuropsychiatry and Clinical Neurosciences, Jul 1, 2019

Self-monitoring is a crucial component of human empathy and necessary for the formation and repai... more Self-monitoring is a crucial component of human empathy and necessary for the formation and repair of social relations. Several studies have brought to light possible neuronal substrates associated with self-monitoring, but the information that they have provided is inconclusive. The authors, therefore, studied a large group of patients with dementia to assess what brain structures are necessary for the self-monitoring function. Methods: Seventy-seven patients with dementia of various types were screened using voxel-based morphometry to assess possible volume reduction in the brain structures of patients with self-monitoring problems, and the decrease of socioemotional expressiveness and modification of self-presentation was estimated using the Revised Self-Monitoring Scale. Regression analysis was employed to investigate the correlation between gray matter loss and deficient self-monitoring. Results: The socioemotional expressiveness scores were associated with decreased gray matter volume in the right olfactory cortex, inferior frontal gyrus, superior temporal pole, parahippocampal gyrus, insula, and medial temporal gyrus bilaterally. Self-presentation scores were associated with bilateral gray matter volume reduction in the olfactory cortex, insula, rectus gyrus and inferior frontal gyrus, right superior temporal pole, and parahippocampal gyrus, as well as the left medial temporal gyrus and anterior superior frontal gyrus. Conclusions: These results suggest that patients with dementia present decreased ability of self-monitoring, probably due to impaired insula and orbitofrontal cortex and their disconnection from structures of the salience network.

Alzheimers & Dementia, Dec 1, 2022

Alzheimers & Dementia, Dec 1, 2021

BackgroundThere are multiple neurodegenerative diseases that directly affect speech [1]. However,... more BackgroundThere are multiple neurodegenerative diseases that directly affect speech [1]. However, its utilization as a robust indicator for cognitive impairment is under‐investigated. In many cases, mild cognitive decline progresses to a neurodegenerative disease and its detection is of utmost importance, since it is at this stage that treatment is most effective. One of our core goals is developing techniques for differentiating between patients with cognitive decline and healthy cohorts, by utilizing only speech samples [2]. Such samples are obtained from verbal elicitation tasks designed for cognitive assessment, e.g. picture descriptions and narration of everyday activities.MethodAudio recordings from cognitive assessment tasks are fed through our platform to a Natural Language Processing and Machine Learning pipeline, employing an automatic discovery procedure of predictive salient biomarkers, to train an advanced classification system. The biomarker collection includes features that characterize voice, speech, language structure, composition and usage, and are engineered to highlight symptoms of neurodegenerative disorders. Biomarkers undergo multiple stages of filtering, processing and transformation to train and fine‐tune the final model. Diagnostic performance of the output classifier is obtained on an unseen test set, to ensure a robust generalization of the platform.ResultOur platform utilizes the set of automatically selected, cross‐linguistic digital biomarkers to obtain sensitivity and specificity scores of 81% and 84% respectively, compared against medical expert diagnosis. The most salient biomarkers with respect to identifying our pathological cohort, relate to feature categories of Syntactic Complexity, Content Word usage, Lexical Repetition, Syntactic Errors and Function Words, with weight contributions of ∼ 16%, 14%, 13%, 12% and 11% respectively. Our platform provides additional, detailed population and patient‐based descriptive analytics to enhance transparency and explainability of the results.ConclusionEarly detection of cognitive decline facilitates early intervention, treatment and proactive care, delaying disease progression and reducing symptom severity. We believe that our platform provides an effective solution for risk factor estimation and our findings incentivize further research into speech analysis techniques for the prediction of cognitive decline.[1] Boschi, Veronica, et al.,Frontiers in psychology 8 (2017): 269.[2] Vassiliki Rentoumi et al., Alzheimer's & Dementia, Wiley, volume 16, 2020.

Geriatrics

One major challenge during the COVID-19 pandemic was the limited accessibility to healthcare faci... more One major challenge during the COVID-19 pandemic was the limited accessibility to healthcare facilities, especially for the older population. The aim of the current study was the exploration of the extent to which the healthcare systems responded to the healthcare needs of the older people with or without cognitive impairment and their caregivers in the Adrion/Ionian region. Data were collected through e-questionnaires regarding the adequacy of the healthcare system and were anonymously administered to older individuals and stakeholder providers in the following countries: Slovenia, Italy (Calabria), Croatia, Bosnia and Herzegovina, Greece, Montenegro, and Serbia. Overall, 722 older people and 267 healthcare stakeholders participated in the study. During the COVID-19 pandemic, both healthcare stakeholders and the older population claimed that the healthcare needs of the older people and their caregivers increased dramatically in all countries, especially in Italy (Calabria), Croatia...

Geriatrics

Background: the apolipoprotein e4 allele (APOE4) constitutes an established genetic risk factor f... more Background: the apolipoprotein e4 allele (APOE4) constitutes an established genetic risk factor for Alzheimer’s Disease Dementia (ADD). We aimed to explore the frequency of the APOE isoforms in the Greek population of Southern Greece. Methods: peripheral blood from 175 Greek AD patients, 113 with mild cognitive impairment (MCI), and 75 healthy individuals. DNA isolation was performed with a High Pure PCR Template Kit (Roche), followed by amplification with a real-time qPCR kit (TIB MolBiol) in Roche’s Light Cycler PCR platform. Results: APOE4 allele frequency was 20.57% in the ADD group, 17.69% in the MCI group, and 6.67% in the control group. APOE3/3 homozygosity was the most common genotype, while the frequency of APOE4/4 homozygosity was higher in the AD group (8.60%). APOE4 carrier status was associated with higher odds for ADD and MCI (OR: 4.49, 95% CI: [1.90–10.61] and OR: 3.82, 95% CI: [1.59–9.17], respectively). Conclusion: this study examines the APOE isoforms and is the fi...

Background: Empathy, which refers to a cognitive and emotional process of continuously detecting ... more Background: Empathy, which refers to a cognitive and emotional process of continuously detecting the changing intentions of others, differs in the behavioral variant frontotemporal degeneration (bvFTD) compared with other dementia types. Interpersonal Reactivity Index scale (IRI) could help in understanding their differential patterns of empathy. We suggested that both emotional and cognitive aspects of empathy would be significantly decreased in bvFTD patients compared to other dementia groups in the Greek population. Methods: We examined 162 subjects with dementia of various types and normal control. (normal control: 61; Alzheimer’s disease (AD): 61; bvFTD 19; semantic variant of Primary Progressive Aphasia: 14; nonfluent variant of Primary Progressive Aphasia: 7).Two subscales of IRI, Empathic Concern and Perspective-Taking, used to measure the cognitive and emotional components of empathy. Results: Patients with bvFTD showed extreme deficits in both empathic concern and perspect...

Science, 2020

Two ways to get tangled? Neurodegeneration in Alzheimer's disease dementia is associated with... more Two ways to get tangled? Neurodegeneration in Alzheimer's disease dementia is associated with neurofibrillary tangles composed of aggregated tau protein. Darwich et al. describe an additional form of autosomal-dominant dementia with neurofibrillary tangles linked to a hypomorph mutation in valosin-containing protein (VCP). VCP was found to disaggregate pathologic tau, and the hypomorph mutation increased tau accumulation in cells and mice. These findings highlight the role of protein turnover in maintaining neuronal health and suggest that VCP may provide a therapeutic target for Alzheimer's disease. Science , this issue p. eaay8826

International Journal of Geriatric Psychiatry, 2020

BackgroundThe novel coronavirus disease (COVID‐19) was first detected in Mainland China in Decemb... more BackgroundThe novel coronavirus disease (COVID‐19) was first detected in Mainland China in December 2019, and soon it spread throughout the world, with multiple physical and psychological consequences across the affected populations.AimsThe aim of the current study was to analyze the impact of COVID‐19 pandemic on older adults with mild cognitive impairment (MCI)/dementia and their caregivers as well.Materials and MethodsTwo hundred and four caregivers took part in the study, completing a self‐reported questionnaire about the person with MCI/dementia and their own, since the lockdown period which started in February and ended in May of 2020 in Greece.ResultsResults indicated a significant overall decline of the people with MCI/dementia. Further, the domains in which people with MCI/dementia were mostly affected were: communication, mood, movement and compliance with the new measures. Caregivers also reported a great increase in their psychological and physical burden during this per...

Alzheimer Disease & Associated Disorders, 2013

Patients with neurodegenerative disease show distinct patterns of personality change, some of whi... more Patients with neurodegenerative disease show distinct patterns of personality change, some of which may be traced to focal neurologic damage, while others may be mediated by cultural reactions to functional impairment. While such changes are early and pervasive in behavioral variant frontotemporal dementia (bvFTD), and milder changes are seen in Alzheimer's (AD), no study has examined all Big 5 factors of personality in mild cognitive impairment (MCI) patients. Also, the influence of culture and ethnicity on disease-related personality changes has seldom been examined. Premorbid and current personality were measured in 47 Greek patients with bvFTD, AD, and MCI according to informant reports using the TPQue5, a 5-factor inventory in the Greek language and accounting for Greek cultural factors. bvFTDs showed greater decreases in conscientiousness than ADs and MCIs. ADs and MCIs showed increased neuroticism, while the bvFTD patients were rated as having become much less neurotic in the course of their disease. The pattern of personality change in MCIs was very similar to that of ADs, supporting recent evidence that personality changes occur as early as the MCI disease stage. In all groups, personality changes were similar to those previously described in non-Mediterranean cultures, supporting the hypothesis that they may result directly from disease-specific neurologic processes.

Alzheimer Disease & Associated Disorders, 2019

Objective: A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increas... more Objective: A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increase the risk for Alzheimer disease (AD), while mixed evidence has been reported for association of the variant with other neurodegenerative diseases. Here, we investigated the frequency of the R47H variant in a diverse and well-characterized multicenter neurodegenerative disease cohort. Methods: We examined the frequency of the R47H variant in a diverse neurodegenerative disease cohort, including a total of 3058 patients clinically diagnosed with AD, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis and 5089 control subjects. Results: We observed a significant association between the R47H variant and AD, while no association was observed with any other neurodegenerative disease included in this study. Conclusions: Our results support the consensus that the R47H variant is s...

Alzheimer's & Dementia, 2022

As research and services in the Mediterranean region continue to increase, so do opportunities fo... more As research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID‐19 pandemic, the meeting was held virtually, which enabled attendees from around the world to hear about research efforts in Greece and the surrounding Mediterranean countries. Research updates spanned understanding the biology of, treatments for, and care of people with Alzheimer's disease (AD_ and other dementias. Researchers in the Mediterranean region have outlined the local epidemiology of AD and dementia, and have identified regional populations that may expedite genetic studies. Development of biomarkers is expected to aid early and accurate diagnosis. Numerous efforts have been made to develop culturally specific interventions to both reduce risk ...

Journal of Clinical Medicine

Background: Social cognition helps people to understand their own and others’ behavior and to mod... more Background: Social cognition helps people to understand their own and others’ behavior and to modulate the way of thinking and acting in different social situations. Rapid and accurate diagnoses of neurodegenerative diseases are essential, as social cognition is affected by these diseases. The Revised Self-Monitoring Scale (RSMS) is a scale that detects social–emotional cognition deficits. Aim: The aim of the current study is to examine how socioemotional parameters are affected by neurodegenerative diseases and whether the RSMS can discern these disorders based on the socioemotional parameters in the Greek population. Methods/Design: A total of 331 dementia subjects were included. Mini Mental State Examination (MMSE) and Addenbrooke’s Cognitive Examination (Revised, ACE-R) measurements were used in order to assess the cognitive deficits. The Neuropsychiatric Inventory (NPI) was used for the evaluation of the neuropsychiatric symptoms. The RSMS and its two subscales was used in orde...

Medicina

Background and Objectives: Dementia affects more than 55 million patients worldwide, with a signi... more Background and Objectives: Dementia affects more than 55 million patients worldwide, with a significant societal, economic, and psychological impact. However, many patients with Alzheimer’s disease (AD) and other related dementias have limited access to effective and individualized treatment. Care provision for dementia is often unequal, fragmented, and inefficient. The COVID-19 pandemic accelerated telemedicine use, which holds promising potential for addressing this important gap. In this narrative review, we aim to analyze and discuss how telemedicine can improve the quality of healthcare for AD and related dementias in a structured manner, based on the seven dimensions of healthcare quality defined by the World Health Organization (WHO), 2018: effectiveness, safety, people-centeredness, timeliness, equitability, integrated care, and efficiency. Materials and Methods: MEDLINE and Scopus databases were searched for peer-reviewed articles investigating the role of telemedicine in t...

Diagnostics, May 4, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

†These authors contributed equally and are joint first authors. ‡These authors are joint senior a... more †These authors contributed equally and are joint first authors. ‡These authors are joint senior authors.

Alzheimer's & Dementia, 2021

BACKGROUND Various neurodegenerative and psychiatric diseases are related with changes in spoken ... more BACKGROUND Various neurodegenerative and psychiatric diseases are related with changes in spoken language [1], although they have seldom been investigated. We evaluate the effectiveness of our language-agnostic Machine Learning (ML) system to detect subtle changes in spoken language that manifest early signs of cognitive decline, thus assisting with its diagnosis. We evaluate our methodology using recordings of speech samples from multiple languages obtained from patient cohorts in early stages of cognitive decline and matched healthy controls. METHOD Our methodology involves capturing patient audio recordings while they are performing one or more predefined cognitive assessment tasks, involving, e.g., the description of a picture or recounting of an everyday activity. Afterwards, multi-language audio recordings and generated transcripts are analyzed with audio and NLP feature extraction methods [3], ranging from semantic, morpho-syntactic, phonological representations of the input, as well as, more sophisticated linguistic measures. The feature pool is filtered by a Pearson's rho threshold of 0.85. We build a Random Forest classifier out of 100 Decision trees, using the Gini impurity criterion, 5-fold cross-validation for training, elimination and composition-based feature selection, as well as post-selection retraining / fine-tuning. The model's diagnostic performance is evaluated on a test set unseen during training. RESULT Our results are validated against the diagnosis that is provided by medical experts. Our performance in terms of accuracy (∼82%), f1 (84%) and ROC-AUC score (∼82%) are clear indicators of the effectiveness of speech analysis towards detecting cognitive decline. Moreover, our tree-based classifier produces probability scores that closely follow the proportion of pathological cases in the input data, with a correlation of 94%. CONCLUSION In the current evaluation we verified our conjectures regarding the strong capacity of speech to predict cognitive decline. Audio analysis and machine learning are proven to be invaluable tools in the prediction of early signs of cognitive decline, which are coupled with a wide spectrum of neurodegenerative and psychiatric diseases. [1] Boschi, Veronica, et al., Frontiers in psychology 8 (2017): 269. [2] Vassiliki Rentoumi et al., Alzheimer's & Dementia, Wiley, volume 16, 2020. [3] Alberdi, Ane et al., Artificial intelligence in medicine 71 (2016): 1-29.

Journal of the Neurological Sciences, 2021

BACKGROUND A significant proportion of FTD (Frontotemporal Degeneration) cases can be attributed ... more BACKGROUND A significant proportion of FTD (Frontotemporal Degeneration) cases can be attributed to mutations in major genes such as GRN, MAPT and C9orf72. Our previous report on a Greek FTD cohort revealed the presence of the single nucleotide polymorphism (SNP) p.I383V (rs80356740) in the TARDBP gene in three unrelated patients. Our objective was to develop a novel, fast and accurate method for the detection of this particular SNP and evaluate the assay in a larger cohort. METHODS AND RESULTS A real-time qPCR-melting curve analysis method was developed, validated and tested in 142 FTD patients and 111 healthy control subjects. The SNP was detected in another two patients raising its yield in FTD patients to 3.5% (5 out of 142 patients) while one in 111 healthy controls was found to be a carrier. However, its frequency in the general population has been reported extremely low in international SNP databases (0.002%). CONCLUSION This fact along with the indicated pathogenicity of this SNP in some bioinformatics tools, suggest that TARDBP p.I383V is recurrent and likely pathogenic for the Greek FTD population. Our high-throughput method could be used for genotyping in other larger patient cohorts and in other populations. Additionally, functional in vitro studies are required for the final adjudication of this TARDBP alteration as a pathogenic alteration.

Neuroimmunology and neuroinflammation, Jul 12, 2020

The classical cerebrospinal fluid biomarkers of Alzheimer's Disease (namely total tau, phospho-ta... more The classical cerebrospinal fluid biomarkers of Alzheimer's Disease (namely total tau, phospho-tau and amyloid beta peptide) have received much attention, since they can detect the biochemical fingerprint of Alzheimer's disease and serve as a diagnostic aid for correct diagnosis of cognitive disorders during life. In this case series, we present 6 examples of patients with cognitive impairment of various types and severities and how biomarker data were helpful in every day diagnostic approach, combined with clinical, neuropsychological and imaging data and based on the most recent guidelines and recommendations.

Behavioural Brain Research, Jul 1, 2020

Present review aimed to conduct a comprehensive review of the effectiveness of non-pharmacologica... more Present review aimed to conduct a comprehensive review of the effectiveness of non-pharmacological interventions (NPIs) on reducing anxiety in adult burn patients. Method: We searched PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases through September 2019 for randomized clinical trials comparing NPIs to a control group. The primary outcomes were general anxiety and pain anxiety. The Cochrane Risk of Bias Tool was used to assess the risk of bias. All data was pooled with Revman 5.3. Results: 20 studies were eligible for quantitative synthesis. Compared to routine care, Music (4 Randomized Clinical Trials (RCTs), Standardized Mean Difference (SMD) =-2.00, 95 % Confidence Interval (CI) =-3.21 to-0.79), massage (4 RCTs, SMD=-1.84, 95 % CI=-2.77 to-0.91), hypnosis (2 RCTs, SMD= −1.06, 95 % CI= −2.90 to 0.78), relaxation (2 RCTs, SMD= −0.77, 95 %CI= −1.52 to −0.02), transcranial direct current stimulation (1 RCT, SMD= −1.92, 95 %CI= −2.54 to −1.30), and therapeutic touch practices (1 RCT, SMD=−0.45 95 %CI= −0.86 to −0.04), were associated with a significant effect on the anxiety of burn patients. Aromatherapy interventions and virtual reality showed no evidence of a reduction in the anxiety. A large amount of heterogeneity exist among trials. Risk of bias varied across studies. Only one study reported on safety issues. Conclusion: Due to weak evidence, we are unable to make strong recommendations in favor of NPIs for burn anxiety. Further well-designed large sample size randomized clinical trials are warranted.

Frontiers in Communication, 2018

There is a growing body of research on language impairment in bilingual speakers with neurodegene... more There is a growing body of research on language impairment in bilingual speakers with neurodegenerative diseases. Evidence as to which language is better preserved is rather inconclusive. Various factors seem to influence language performance, most notably age of acquisition, level of proficiency, immersion and degree of exposure to each language. The present study examined fluency, lexical, discourse and grammatical abilities of a Greek-French late bilingual man with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA). Speech samples derived from three different narrative tasks in both languages were analyzed using quantitative production analysis (QPA) and fluency measures. The first aim of the study was to compare the participant's connected speech production to that of Greek-speaking normal controls. The second aim was to determine whether Greek (L1) and French (L2) were differentially impaired. To our knowledge, this is the first report of connected speech deficits in a Greek-speaking patient with PPA and the first study which uses QPA to compare L1 and L2 narratives in a bilingual speaker with PPA. Compared to neurologically healthy controls, our participant was impaired in lexical, discourse and grammatical productivity measures, but did not differ in measures of grammatical accuracy. The presence of dysfluencies, reduced speech rate and simplified syntax is consistent with the pattern of impairment reported for the nfvPPA. Results showed that narrative production measures did not differ significantly between languages. However, they suggest a slightly worse performance in his second, non-dominant, language despite a similar pattern of impairment in both languages. Lengthy exposure to L2 and regular activation of L2 through daily use may explain the preservation of discourse abilities in his non-dominant language. This study calls attention to factors such as language dominance, proficiency, patterns of use, and exposure to a language. These factors play a key role in assessing bilingual individuals with PPA and making clinical decisions.

Journal of Neuropsychiatry and Clinical Neurosciences, Jul 1, 2019

Self-monitoring is a crucial component of human empathy and necessary for the formation and repai... more Self-monitoring is a crucial component of human empathy and necessary for the formation and repair of social relations. Several studies have brought to light possible neuronal substrates associated with self-monitoring, but the information that they have provided is inconclusive. The authors, therefore, studied a large group of patients with dementia to assess what brain structures are necessary for the self-monitoring function. Methods: Seventy-seven patients with dementia of various types were screened using voxel-based morphometry to assess possible volume reduction in the brain structures of patients with self-monitoring problems, and the decrease of socioemotional expressiveness and modification of self-presentation was estimated using the Revised Self-Monitoring Scale. Regression analysis was employed to investigate the correlation between gray matter loss and deficient self-monitoring. Results: The socioemotional expressiveness scores were associated with decreased gray matter volume in the right olfactory cortex, inferior frontal gyrus, superior temporal pole, parahippocampal gyrus, insula, and medial temporal gyrus bilaterally. Self-presentation scores were associated with bilateral gray matter volume reduction in the olfactory cortex, insula, rectus gyrus and inferior frontal gyrus, right superior temporal pole, and parahippocampal gyrus, as well as the left medial temporal gyrus and anterior superior frontal gyrus. Conclusions: These results suggest that patients with dementia present decreased ability of self-monitoring, probably due to impaired insula and orbitofrontal cortex and their disconnection from structures of the salience network.

Alzheimers & Dementia, Dec 1, 2022

Alzheimers & Dementia, Dec 1, 2021

BackgroundThere are multiple neurodegenerative diseases that directly affect speech [1]. However,... more BackgroundThere are multiple neurodegenerative diseases that directly affect speech [1]. However, its utilization as a robust indicator for cognitive impairment is under‐investigated. In many cases, mild cognitive decline progresses to a neurodegenerative disease and its detection is of utmost importance, since it is at this stage that treatment is most effective. One of our core goals is developing techniques for differentiating between patients with cognitive decline and healthy cohorts, by utilizing only speech samples [2]. Such samples are obtained from verbal elicitation tasks designed for cognitive assessment, e.g. picture descriptions and narration of everyday activities.MethodAudio recordings from cognitive assessment tasks are fed through our platform to a Natural Language Processing and Machine Learning pipeline, employing an automatic discovery procedure of predictive salient biomarkers, to train an advanced classification system. The biomarker collection includes features that characterize voice, speech, language structure, composition and usage, and are engineered to highlight symptoms of neurodegenerative disorders. Biomarkers undergo multiple stages of filtering, processing and transformation to train and fine‐tune the final model. Diagnostic performance of the output classifier is obtained on an unseen test set, to ensure a robust generalization of the platform.ResultOur platform utilizes the set of automatically selected, cross‐linguistic digital biomarkers to obtain sensitivity and specificity scores of 81% and 84% respectively, compared against medical expert diagnosis. The most salient biomarkers with respect to identifying our pathological cohort, relate to feature categories of Syntactic Complexity, Content Word usage, Lexical Repetition, Syntactic Errors and Function Words, with weight contributions of ∼ 16%, 14%, 13%, 12% and 11% respectively. Our platform provides additional, detailed population and patient‐based descriptive analytics to enhance transparency and explainability of the results.ConclusionEarly detection of cognitive decline facilitates early intervention, treatment and proactive care, delaying disease progression and reducing symptom severity. We believe that our platform provides an effective solution for risk factor estimation and our findings incentivize further research into speech analysis techniques for the prediction of cognitive decline.[1] Boschi, Veronica, et al.,Frontiers in psychology 8 (2017): 269.[2] Vassiliki Rentoumi et al., Alzheimer's & Dementia, Wiley, volume 16, 2020.

Geriatrics

One major challenge during the COVID-19 pandemic was the limited accessibility to healthcare faci... more One major challenge during the COVID-19 pandemic was the limited accessibility to healthcare facilities, especially for the older population. The aim of the current study was the exploration of the extent to which the healthcare systems responded to the healthcare needs of the older people with or without cognitive impairment and their caregivers in the Adrion/Ionian region. Data were collected through e-questionnaires regarding the adequacy of the healthcare system and were anonymously administered to older individuals and stakeholder providers in the following countries: Slovenia, Italy (Calabria), Croatia, Bosnia and Herzegovina, Greece, Montenegro, and Serbia. Overall, 722 older people and 267 healthcare stakeholders participated in the study. During the COVID-19 pandemic, both healthcare stakeholders and the older population claimed that the healthcare needs of the older people and their caregivers increased dramatically in all countries, especially in Italy (Calabria), Croatia...

Geriatrics

Background: the apolipoprotein e4 allele (APOE4) constitutes an established genetic risk factor f... more Background: the apolipoprotein e4 allele (APOE4) constitutes an established genetic risk factor for Alzheimer’s Disease Dementia (ADD). We aimed to explore the frequency of the APOE isoforms in the Greek population of Southern Greece. Methods: peripheral blood from 175 Greek AD patients, 113 with mild cognitive impairment (MCI), and 75 healthy individuals. DNA isolation was performed with a High Pure PCR Template Kit (Roche), followed by amplification with a real-time qPCR kit (TIB MolBiol) in Roche’s Light Cycler PCR platform. Results: APOE4 allele frequency was 20.57% in the ADD group, 17.69% in the MCI group, and 6.67% in the control group. APOE3/3 homozygosity was the most common genotype, while the frequency of APOE4/4 homozygosity was higher in the AD group (8.60%). APOE4 carrier status was associated with higher odds for ADD and MCI (OR: 4.49, 95% CI: [1.90–10.61] and OR: 3.82, 95% CI: [1.59–9.17], respectively). Conclusion: this study examines the APOE isoforms and is the fi...

Background: Empathy, which refers to a cognitive and emotional process of continuously detecting ... more Background: Empathy, which refers to a cognitive and emotional process of continuously detecting the changing intentions of others, differs in the behavioral variant frontotemporal degeneration (bvFTD) compared with other dementia types. Interpersonal Reactivity Index scale (IRI) could help in understanding their differential patterns of empathy. We suggested that both emotional and cognitive aspects of empathy would be significantly decreased in bvFTD patients compared to other dementia groups in the Greek population. Methods: We examined 162 subjects with dementia of various types and normal control. (normal control: 61; Alzheimer’s disease (AD): 61; bvFTD 19; semantic variant of Primary Progressive Aphasia: 14; nonfluent variant of Primary Progressive Aphasia: 7).Two subscales of IRI, Empathic Concern and Perspective-Taking, used to measure the cognitive and emotional components of empathy. Results: Patients with bvFTD showed extreme deficits in both empathic concern and perspect...

Science, 2020

Two ways to get tangled? Neurodegeneration in Alzheimer's disease dementia is associated with... more Two ways to get tangled? Neurodegeneration in Alzheimer's disease dementia is associated with neurofibrillary tangles composed of aggregated tau protein. Darwich et al. describe an additional form of autosomal-dominant dementia with neurofibrillary tangles linked to a hypomorph mutation in valosin-containing protein (VCP). VCP was found to disaggregate pathologic tau, and the hypomorph mutation increased tau accumulation in cells and mice. These findings highlight the role of protein turnover in maintaining neuronal health and suggest that VCP may provide a therapeutic target for Alzheimer's disease. Science , this issue p. eaay8826

International Journal of Geriatric Psychiatry, 2020

BackgroundThe novel coronavirus disease (COVID‐19) was first detected in Mainland China in Decemb... more BackgroundThe novel coronavirus disease (COVID‐19) was first detected in Mainland China in December 2019, and soon it spread throughout the world, with multiple physical and psychological consequences across the affected populations.AimsThe aim of the current study was to analyze the impact of COVID‐19 pandemic on older adults with mild cognitive impairment (MCI)/dementia and their caregivers as well.Materials and MethodsTwo hundred and four caregivers took part in the study, completing a self‐reported questionnaire about the person with MCI/dementia and their own, since the lockdown period which started in February and ended in May of 2020 in Greece.ResultsResults indicated a significant overall decline of the people with MCI/dementia. Further, the domains in which people with MCI/dementia were mostly affected were: communication, mood, movement and compliance with the new measures. Caregivers also reported a great increase in their psychological and physical burden during this per...

Alzheimer Disease & Associated Disorders, 2013

Patients with neurodegenerative disease show distinct patterns of personality change, some of whi... more Patients with neurodegenerative disease show distinct patterns of personality change, some of which may be traced to focal neurologic damage, while others may be mediated by cultural reactions to functional impairment. While such changes are early and pervasive in behavioral variant frontotemporal dementia (bvFTD), and milder changes are seen in Alzheimer's (AD), no study has examined all Big 5 factors of personality in mild cognitive impairment (MCI) patients. Also, the influence of culture and ethnicity on disease-related personality changes has seldom been examined. Premorbid and current personality were measured in 47 Greek patients with bvFTD, AD, and MCI according to informant reports using the TPQue5, a 5-factor inventory in the Greek language and accounting for Greek cultural factors. bvFTDs showed greater decreases in conscientiousness than ADs and MCIs. ADs and MCIs showed increased neuroticism, while the bvFTD patients were rated as having become much less neurotic in the course of their disease. The pattern of personality change in MCIs was very similar to that of ADs, supporting recent evidence that personality changes occur as early as the MCI disease stage. In all groups, personality changes were similar to those previously described in non-Mediterranean cultures, supporting the hypothesis that they may result directly from disease-specific neurologic processes.

Alzheimer Disease & Associated Disorders, 2019

Objective: A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increas... more Objective: A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increase the risk for Alzheimer disease (AD), while mixed evidence has been reported for association of the variant with other neurodegenerative diseases. Here, we investigated the frequency of the R47H variant in a diverse and well-characterized multicenter neurodegenerative disease cohort. Methods: We examined the frequency of the R47H variant in a diverse neurodegenerative disease cohort, including a total of 3058 patients clinically diagnosed with AD, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis and 5089 control subjects. Results: We observed a significant association between the R47H variant and AD, while no association was observed with any other neurodegenerative disease included in this study. Conclusions: Our results support the consensus that the R47H variant is s...

Alzheimer's & Dementia, 2022

As research and services in the Mediterranean region continue to increase, so do opportunities fo... more As research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID‐19 pandemic, the meeting was held virtually, which enabled attendees from around the world to hear about research efforts in Greece and the surrounding Mediterranean countries. Research updates spanned understanding the biology of, treatments for, and care of people with Alzheimer's disease (AD_ and other dementias. Researchers in the Mediterranean region have outlined the local epidemiology of AD and dementia, and have identified regional populations that may expedite genetic studies. Development of biomarkers is expected to aid early and accurate diagnosis. Numerous efforts have been made to develop culturally specific interventions to both reduce risk ...

Journal of Clinical Medicine

Background: Social cognition helps people to understand their own and others’ behavior and to mod... more Background: Social cognition helps people to understand their own and others’ behavior and to modulate the way of thinking and acting in different social situations. Rapid and accurate diagnoses of neurodegenerative diseases are essential, as social cognition is affected by these diseases. The Revised Self-Monitoring Scale (RSMS) is a scale that detects social–emotional cognition deficits. Aim: The aim of the current study is to examine how socioemotional parameters are affected by neurodegenerative diseases and whether the RSMS can discern these disorders based on the socioemotional parameters in the Greek population. Methods/Design: A total of 331 dementia subjects were included. Mini Mental State Examination (MMSE) and Addenbrooke’s Cognitive Examination (Revised, ACE-R) measurements were used in order to assess the cognitive deficits. The Neuropsychiatric Inventory (NPI) was used for the evaluation of the neuropsychiatric symptoms. The RSMS and its two subscales was used in orde...

Medicina

Background and Objectives: Dementia affects more than 55 million patients worldwide, with a signi... more Background and Objectives: Dementia affects more than 55 million patients worldwide, with a significant societal, economic, and psychological impact. However, many patients with Alzheimer’s disease (AD) and other related dementias have limited access to effective and individualized treatment. Care provision for dementia is often unequal, fragmented, and inefficient. The COVID-19 pandemic accelerated telemedicine use, which holds promising potential for addressing this important gap. In this narrative review, we aim to analyze and discuss how telemedicine can improve the quality of healthcare for AD and related dementias in a structured manner, based on the seven dimensions of healthcare quality defined by the World Health Organization (WHO), 2018: effectiveness, safety, people-centeredness, timeliness, equitability, integrated care, and efficiency. Materials and Methods: MEDLINE and Scopus databases were searched for peer-reviewed articles investigating the role of telemedicine in t...

Diagnostics, May 4, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

†These authors contributed equally and are joint first authors. ‡These authors are joint senior a... more †These authors contributed equally and are joint first authors. ‡These authors are joint senior authors.

Alzheimer's & Dementia, 2021

BACKGROUND Various neurodegenerative and psychiatric diseases are related with changes in spoken ... more BACKGROUND Various neurodegenerative and psychiatric diseases are related with changes in spoken language [1], although they have seldom been investigated. We evaluate the effectiveness of our language-agnostic Machine Learning (ML) system to detect subtle changes in spoken language that manifest early signs of cognitive decline, thus assisting with its diagnosis. We evaluate our methodology using recordings of speech samples from multiple languages obtained from patient cohorts in early stages of cognitive decline and matched healthy controls. METHOD Our methodology involves capturing patient audio recordings while they are performing one or more predefined cognitive assessment tasks, involving, e.g., the description of a picture or recounting of an everyday activity. Afterwards, multi-language audio recordings and generated transcripts are analyzed with audio and NLP feature extraction methods [3], ranging from semantic, morpho-syntactic, phonological representations of the input, as well as, more sophisticated linguistic measures. The feature pool is filtered by a Pearson's rho threshold of 0.85. We build a Random Forest classifier out of 100 Decision trees, using the Gini impurity criterion, 5-fold cross-validation for training, elimination and composition-based feature selection, as well as post-selection retraining / fine-tuning. The model's diagnostic performance is evaluated on a test set unseen during training. RESULT Our results are validated against the diagnosis that is provided by medical experts. Our performance in terms of accuracy (∼82%), f1 (84%) and ROC-AUC score (∼82%) are clear indicators of the effectiveness of speech analysis towards detecting cognitive decline. Moreover, our tree-based classifier produces probability scores that closely follow the proportion of pathological cases in the input data, with a correlation of 94%. CONCLUSION In the current evaluation we verified our conjectures regarding the strong capacity of speech to predict cognitive decline. Audio analysis and machine learning are proven to be invaluable tools in the prediction of early signs of cognitive decline, which are coupled with a wide spectrum of neurodegenerative and psychiatric diseases. [1] Boschi, Veronica, et al., Frontiers in psychology 8 (2017): 269. [2] Vassiliki Rentoumi et al., Alzheimer's & Dementia, Wiley, volume 16, 2020. [3] Alberdi, Ane et al., Artificial intelligence in medicine 71 (2016): 1-29.

Journal of the Neurological Sciences, 2021

BACKGROUND A significant proportion of FTD (Frontotemporal Degeneration) cases can be attributed ... more BACKGROUND A significant proportion of FTD (Frontotemporal Degeneration) cases can be attributed to mutations in major genes such as GRN, MAPT and C9orf72. Our previous report on a Greek FTD cohort revealed the presence of the single nucleotide polymorphism (SNP) p.I383V (rs80356740) in the TARDBP gene in three unrelated patients. Our objective was to develop a novel, fast and accurate method for the detection of this particular SNP and evaluate the assay in a larger cohort. METHODS AND RESULTS A real-time qPCR-melting curve analysis method was developed, validated and tested in 142 FTD patients and 111 healthy control subjects. The SNP was detected in another two patients raising its yield in FTD patients to 3.5% (5 out of 142 patients) while one in 111 healthy controls was found to be a carrier. However, its frequency in the general population has been reported extremely low in international SNP databases (0.002%). CONCLUSION This fact along with the indicated pathogenicity of this SNP in some bioinformatics tools, suggest that TARDBP p.I383V is recurrent and likely pathogenic for the Greek FTD population. Our high-throughput method could be used for genotyping in other larger patient cohorts and in other populations. Additionally, functional in vitro studies are required for the final adjudication of this TARDBP alteration as a pathogenic alteration.