How telemedicine can improve the quality of care for patients with alzheimer’s disease and related dementias? A narrative review

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 the quality of care for patients with dementia. A narrative synthesis was based on the seven WHO dimensions. Results: Most studies indicate that telemedicine is a valuable tool for AD and related dementias: it can improve effectiveness (better access to specialized care, accurate diagnosis, evidence-based treatment, avoidance of preventable hospitalizations), timeliness (reduction of waiting times and unnecessary transportation), patient-centeredness (personalized care for needs and values), safety (appropriate treatment, reduction of infection risk),integrated care (interdisciplinary approach through several dementia-related services), efficiency (mainly cost-effectiveness) and equitability (overcoming geographical barriers, cultural diversities). However, digital illiteracy, legal and organizational issues, as well as limited awareness, are significant potential barriers. Conclusions: Telemedicine may significantly improve all aspects of the quality of care for patients with dementia. However, future longitudinal studies with control groups including participants of a wide educational level spectrum will aid in our deeper understanding of the real impact of telemedicine in quality care for this population

Prosopagnosia, Other Specific Cognitive Deficits, and Behavioral Symptoms: Comparison between Right Temporal and Behavioral Variant of Frontotemporal Dementia

Right temporal variant of frontotemporal dementia (rtv-FTD) represents an uncommon and recently described frontotemporal dementia (FTD) entity presenting with symptoms in many ways comparable to those of the frontal or behavioral variant of FTD (bv-FTD). The aims of this study were to explore the timing of cognitive and behavioral symptoms of rtv-FTD, and to compare the distinct cognitive deficits including prosopagnosia and behavioral symptoms of rtv-FTD patients with those observed in bv-FTD patients. We reviewed the records of 105 patients clinically diagnosed with FTD. A total of 7 patients (5 men/2 women) with FTD and marked right temporal atrophy in magnetic resonance imaging (MRI) were detected. Clinical features were compared with those observed in a group of 22 age-matched patients (16 men/6 women) with FTD and predominant frontal lobe atrophy. The main presenting symptoms of rtv-FTD were prosopagnosia, apathy, and episodic memory impairment. In contrast, social awkwardness and compulsive behaviors were dominant in later stages of the disease together with disinhibition and loss of insight with a marked personality change. Although the cognitive and behavioral profiles of patients with right temporal or frontal lobes atrophy present substantial similarities, each subtype has a number of distinct characteristics. It appears that prosopagnosia, obsessive behaviors, and psychotic symptoms are more prominent in rtv-FTD patients

Study of neurotoxic factors action on the rat cerebellum

Cytosine arabinoside (AraC) an anticancer drug commonly used in leukemia treatment, has an impact on cerebellar function and severe motor coordination deficits are described among its side effects. In order to characterize the nature of AraC-induced cerebellar lesions in an adult animal model, we have administered i.p. 400mg/kg bw of AraC in adult male Wistar rats for 5 days. Subsequently, the animals were subjected to behavioral tests including walking pattern evaluation, rotarod, open field and Morris watermaze tests. AraC- treated rats demonstrated a disturbed walking pattern, an impaired ability to remain on the rotating rod, along with a decrease of swimming velocity in the watermaze test, implying a weaker motor learning and coordination ability in comparison to the control group. The disturbed performance in the above tests was largely prevented by co-administration of the antioxidant N-acetylcysteine (NAC) 200mg/kg p.o. In the molecular cerebellar layer of AraC - treated animals, the neurofilament (NF) immunopositive axons, stemming from basket and stellate cells, were significantly reduced. Western blotting revealed an altered proportion of the three NF isotypes (NF-H, NF-M, NF-L). Following AraC treatment, Purkinje cells exhibited an enhanced expression of the calcium buffering protein calbindin D along with an up-regulation of other proteins responding to AraC toxic insult, like GAPDH and heat shock protein 70. To investigate the impact of developmental state in the AraC - induced toxicity in the cerebellum, we have administered i.p. 200mg/kg bw of AraC in neonatal male and female Wistar rats for 3 days (during postnatal days 14-16). Nissl staining showed a decrease in the external granular layer width within the animals of the AraC group. The latter exhibited a reduced immunopositivity against GFAP, possibly as an outcome of a toxic AraC effect on glia. Western blot analysis of the cerebella of the AraC - treated neonatal male rats also revealed a statistically significant decrease in the ratio of the NF-Η isoform to the total NF content compared to non-treated controls, though to a lesser extent than in adults. Interestingly, AraC - treated neonatal female rats exhibited an increase in all three NF isoforms compared to non-treated controls, suggesting the existence of a sexual dimorphism.Η κυτοσίνη αραβινοσίδη (AraC), ένας αντινεοπλασματικός παράγοντας που χρησιμοποιείται συχνά στη θεραπεία της λευχαιμίας, έχει βλαπτική επίδραση στη λειτουργία της παρεγκεφαλίδας. Για να διερευνήσουμε τη φύση της προκαλούμενης βλάβης από το AraC σε ένα πειραματικό μοντέλου σε ενήλικα ζώα, χορηγήσαμε ενδοπεριτοναΐκά AraC σε δόση 400mg/kg Σ.Β σε αρσενικούς ενήλικους επίμυες Wistar επί 5 ημέρες. Στη συνέχεια τα πειραματόζωα υποβλήθηκαν σε δοκιμασίες συμπεριφοράς οι οποίες περιλάμβαναν αξιολόγηση των αποτυπωμάτων βάδισης, δοκιμασία περιστρεφόμενου κυλίνδρου, ανοικτού πεδίου και υδάτινου λαβυρίνθου κατά Morris. Οι επίμυες που έλαβαν AraC παρουσίασαν διαταραχές στις ανωτέρω συμπεριφορικές δοκιμασίες που ενισχύουν την πιθανότητα ελλειμματικού συντονισμού και κινητικής μάθησης στα ζώα αυτής της ομάδας σε σύγκριση με την ομάδα ελέγχου. Η συγχορήγηση του αντιοξειδωτικού φαρμάκου Ν-ακετυλοκυστεΐνης (NAC) σε δόση 200mg/kg Σ.Β διαλυμένο στο πόσιμο νερό, απέτρεψε την εκδήλωση διαταραχής στις επιδόσεις των πειραματόζωων που έλαβαν AraC στις ανωτέρω δοκιμασίες. Στην μοριώδη στοιβάδα της παρεγκεφαλίδας των πειραματόζωων που έλαβαν AraC διαπιστώθηκε ανοσοϊστοχημικά ελάττωση της έκφρασης των νευροϊνιδίων (NF). Η ανοσοστύπωση κατά Western αποκάλυψε μια μεταβολή στην αναλογία ανάμεσα στις τρεις ισόμορφες των νευροϊνιδίων (NF-Η, NF-M, NF-L). Επίσης, καταγράφηκε ανοσοϊστοχημικά μια ενίσχυση της έκφρασης της καλμπιντίνης D (πρωτεΐνη που ρυθμίζει τα επίπεδα ασβεστίου) στα κύτταρα Purkinje και αύξηση των επιπέδων και άλλων πρωτεϊνών όπως της GAPDH και της πρωτεΐνης του θερμικού σοκ Hsp70, ως αντίδραση στο τοξικό ερέθισμα του AraC. Προκειμένου να διερευνήσουμε την επίπτωση του αναπτυξιακού σταδίου στην τοξικότητα του AraC στην παρεγκεφαλίδα, χορηγήθηκε υποδόρια AraC σε δόση 200mg/kg Σ.Β σε νεαρούς αρσενικούς και θηλυκούς επίμυες (κατά τις ημέρες 14-16 από τη γέννηση). Η χρώση Nissl έδειξε ελάττωση του πάχους της εξωτερικής κοκκιώδους στοιβάδας στην ομάδα που έλαβε AraC ενώ τα ίδια ζώα εμφάνιζαν ανοσοϊστοχημικά μείωση της GFAP, γεγονός που υποδηλώνει επίδραση του AraC στη γλοία. Η ανοσοστύπωση κατά Western αποκάλυψε ελάττωση στην αναλογία της NF-Η προς τις υπόλοιπες ισόμορφες στα νεαρά αρσενικά ζώα υπό AraC. Ένα ενδιαφέρον εύρημα ήταν η αύξηση και στις τρεις ισόμορφες των νευροϊνιδίων στα νερά θηλυκά ζώα στα οποία χορηγήθηκε AraC. Το αποτέλεσμα αυτό πιθανά εξηγείται από την ύπαρξη σεξουαλικού διμορφισμού

Effect of cytosine arabinoside on cerebellar neurofilaments during development: A sexual dimorphism

Previous reports suggest that the resistance of neuronal cytoskeleton to drug toxicity may vary with age and gender. The aim of the present study was to assess the impact of cytosine arabinoside (AraC) treatment on neurofilament (NF) levels and phosphorylation status in the developing cerebellum of male, female and testosterone propionate (1.25 mg/rat)-androgenized female rats. AraC (200 mg/kg bw) was administered from postnatal day (PND) 14–16 and changes in the level and phosphorylation of NFs were detected at PND 16 by Western blot analysis. The drug had no effect in male pups, while it increased the non-phosphorylated NF subunits of medium and low molecular weight in females. Androgenization of females prevented the AraC-induced increase in NF subunits. The levels of estrogen receptor beta (ER-β), known to mediate neuroprotective actions of estrogens in the brain, were significantly higher in the developing female cerebellum, as compared to males and androgenized females. These data show that the neurofilament cytoskeleton in the developing rat cerebellum exhibits resistance to AraC that appears sexually dimorphic. In young males the resistance is exemplified by a lack of responsiveness, whereas in juvenile females it is presented by an androgenization-sensitive NF upregulation

Central Nervous System Demyelination in a Charcot-Marie-Tooth Type 1A Patient

Introduction. Central nervous system involvement, either clinical or subclinical, has been reported mainly in X-linked Charcot-Marie-Tooth (CMT-X) patients. Case Presentation. We present the case of a 31-year-old man with a genetically confirmed history of CMT1A who developed CNS involvement mimicking multiple sclerosis (MS). Clinical, imaging, and laboratory findings suggested an autoimmune CNS demyelination. Discussion. Although the simultaneous existence of CMT1A and MS could be coincidental we postulate that overexpression of PMP22, the target protein in CMT1A, might influence the immunological self-tolerance to CNS proteins via molecular mimicry, leading to a CNS autoimmune demyelinating disorder

Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer’s Disease

The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of NPSs at preclinical stages of cognitive decline and Alzheimer’s disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at-risk state for incident cognitive impairment and is defined by the emergence of persistent NPSs among non-demented individuals in later life. These NPSs include affective dysregulation, decreased motivation, impulse dyscontrol, abnormal perception and thought content, and social inappropriateness. Accumulating evidence has recently begun to shed more light on the genetic background of MBI, focusing on its potential association with genetic factors related to AD. The Apolipoprotein E (APOE) genotype and the MS4A locus have been associated with affective dysregulation, ZCWPW1 with social inappropriateness and psychosis, BIN1 and EPHA1 with psychosis, and NME8 with apathy. The association between MBI and polygenic risk scores (PRSs) in terms of AD dementia has been also explored. Potential implicated mechanisms include neuroinflammation, synaptic dysfunction, epigenetic modifications, oxidative stress responses, proteosomal impairment, and abnormal immune responses. In this review, we summarize and critically discuss the available evidence on the genetic background of MBI with an emphasis on AD, aiming to gain insights into the potential underlying neurobiological mechanisms, which till now remain largely unexplored. In addition, we propose future areas of research in this emerging field, with the aim to better understand the molecular pathophysiology of MBI and its genetic links with cognitive decline

Ambiental Factors in Parkinson’s Disease Progression: A Systematic Review

Background and Objectives: So far, there is little evidence of the ambient effect on motor and non-motor symptoms of Parkinson’s Disease (PD). This systematic review aimed to determine the association between ambiental factors and the progression of PD. Materials and Methods: A systematic literature search of PubMed, Cochrane, Embase, and Web of Science was conducted up to 21 December 2021 according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Eight articles were used in the analyses. Long-term exposure to fine particles (particulate matter ≤ 2.5 μm; PM2.5) was positively associated with disease aggravation in two studies. Short-term PM2.5 exposure was positively associated with disease aggravation in three studies. Significant associations were found between PD aggravation and NO2, SO2, CO, nitrate and organic matter (OM) concentrations in two studies. Associations were more pronounced, without reaching statistical significance however, in women, patients over 65 years old and cold temperatures. A 1% increase in temperature was associated with a significant 0.18% increase in Levodopa Equivalent Dose (LED). Ultraviolet light and humidity were not significantly associated with an increase in LED. There was no difference in hallucination severity with changing seasons. There was no evidence for seasonal fluctuation in Unified Parkinson’s Disease Rating Scale (UPDRS) scores. Conclusions: There is a link between air pollutants and temperature for PD progression, but this has yet to be proven. More longitudinal studies are warranted to confirm these findings

Ambiental Factors in Parkinson’s Disease Progression: A Systematic Review

Background and Objectives: So far, there is little evidence of the ambient effect on motor and non-motor symptoms of Parkinson’s Disease (PD). This systematic review aimed to determine the association between ambiental factors and the progression of PD. Materials and Methods: A systematic literature search of PubMed, Cochrane, Embase, and Web of Science was conducted up to 21 December 2021 according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Eight articles were used in the analyses. Long-term exposure to fine particles (particulate matter ≤ 2.5 μm; PM2.5) was positively associated with disease aggravation in two studies. Short-term PM2.5 exposure was positively associated with disease aggravation in three studies. Significant associations were found between PD aggravation and NO2, SO2, CO, nitrate and organic matter (OM) concentrations in two studies. Associations were more pronounced, without reaching statistical significance however, in women, patients over 65 years old and cold temperatures. A 1% increase in temperature was associated with a significant 0.18% increase in Levodopa Equivalent Dose (LED). Ultraviolet light and humidity were not significantly associated with an increase in LED. There was no difference in hallucination severity with changing seasons. There was no evidence for seasonal fluctuation in Unified Parkinson’s Disease Rating Scale (UPDRS) scores. Conclusions: There is a link between air pollutants and temperature for PD progression, but this has yet to be proven. More longitudinal studies are warranted to confirm these findings

Frequency of Impulsive-Compulsive Behavior and Associated Psychological Factors in Parkinson’s Disease: Lack of Control or Too Much of It?

Background and Objectives: Impulse Control Disorders (ICDs) including pathological gambling, hypersexuality, compulsive eating, compulsive buying, and other related behaviors are well-known distinct non-motor symptoms in Parkinson’s Disease (PD). Some large-scale studies present a prevalence of at least 10%, however, there are other reports providing much higher rates. The majority of the conducted studies investigating ICDs focus mainly on pharmacological factors, however, from a psychological perspective, there is yet enough room for investigation. In order to address the above issues, we designed a two-part study. Materials and Methods: First, we aimed to identify the incidence of ICD and related behaviors in a cohort of 892 Greek PD patients. Second, we administered a comprehensive battery of psychometric tools to assess psychological factors such as personality dimensions, quality of life, defenses, coherence, and resilience as well as to screen general cognitive capacity in PD patients with ICD manifestations. Results: With regard to the first part, we identified ICD manifestations in 12.4% of the patients. Preliminary findings from the second part indicate elevated activity, rather than impulsivity, as well as interrelations between several variables, including measures of activity, coping mechanisms, and quality of life. Conclusions: We present a working hypothesis for the contribution of high activity channeled to specific behavioral patterns through specific coping mechanisms, concerning the emergence of ICDs and related behaviors in PD, and further stress the importance of compulsivity rather than impulsivity in this process

CSF and Circulating NfL as Biomarkers for the Discrimination of Parkinson Disease From Atypical Parkinsonian Syndromes

Purpose of Review To evaluate whether CSF and circulating neurofilament light chain (NfL), a marker of axonal damage, could discriminate Parkinson disease (PD) from atypical parkinsonian syndromes (APSs). Recent Findings MEDLINE and Scopus were systematically searched, and 15 studies were included (1,035 patients with PD and 930 patients with APS). CSF NfL levels were 1.26 SDs higher in the APS group compared to the PD group (g = 1.26 [95% confidence interval 0.99-1.53]), and circulating NfL levels were 1.53 SDs higher in the APS group compared to the PD group (g = 1.53 [95% confidence interval 1.15-1.91]); 4 studies, 307 patients with PD, 197 patients with APS. Pooled areas under the curve were 0.941 (0.916-0.965) and 0.874 (0.802-0.946) for CSF and circulating NfL, corresponding to average sensitivities of 86% (79%-90%) and 91% (86%-95%), and specificity of 88% (82%-92%) and 76% (62%-85%), respectively. Summary These results strongly support the high diagnostic accuracy of both CSF and circulating NfL in differentiating PD from APS, highlighting their usefulness as promising biomarkers