GLP-1 Receptor Agonists: A New Treatment in Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Recent data highlight similarities between neurodegenerative diseases, including PD and type 2 diabetes mellitus (T2DM), suggesting a crucial interplay between the gut-brain axis. Glucagon-like peptide-1 receptor (GLP-1R) agonists, known for their use in T2DM treatment, are currently extensively studied as novel PD modifying agents. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles and clinical trials regarding GLP-1R agonists and PD published in the English language with no time restrictions. We also screened the references of the selected articles for possible additional articles in order to include most of the key recent evidence. Many data on animal models and preclinical studies show that GLP1-R agonists can restore dopamine levels, inhibit dopaminergic loss, attenuate neuronal degeneration and alleviate motor and non-motor features of PD. Evidence from clinical studies is also very promising, enhancing the possibility of adding GLP1-R agonists to the current armamentarium of drugs available for PD treatment.

Cognitive Impairment in Neurological Diseases.

The complex link between cognitive impairment and neurological disorders underscores the intricacies of neurological sciences [...].

Correlates of Functional Impairment in Patients with the Behavioral Variant of Frontotemporal Dementia: A PRISMA-Compliant Systematic Review.

The behavioral variant of frontotemporal dementia (bvFTD) has a devastating effect on multiple domains of daily living. The purpose of this PRISMA-compliant systematic review is to summarize the most important factors associated with functional impairment in this clinical group by critically analyzing the existing literature spanning the period from 2000 to 2023. To be included in the review, a study had to investigate any kind of correlates of functional status in bvFTD patients, using a previously validated instrument of functional assessment. Out of 40 articles assessed for eligibility, 18 met the inclusion criteria. The anatomical pattern of cerebral atrophy at baseline appeared to be the strongest predictor of the rate of functional decline over time, with the frontal-dominant anatomical subtype being associated with a faster rate of functional impairment. Additionally, executive dysfunction as well as apathy appeared to contribute significantly to functional disability in bvFTD patients. A comparative examination of bvFTD in relation to other clinical subtypes of FTD and other types of dementia in general suggests that it is the predominant atrophy of the frontal lobes along with the subsequent unique combination of cognitive and neuropsychiatric manifestations that account for the pronounced functional limitations observed in these individuals, even from the early stages of the disease.

CSF Biomarkers in the Early Diagnosis of Mild Cognitive Impairment and Alzheimer's Disease.

Alzheimer's disease (AD) is a rapidly growing disease that affects millions of people worldwide, therefore there is an urgent need for its early diagnosis and treatment. A huge amount of research studies are performed on possible accurate and reliable diagnostic biomarkers of AD. Due to its direct contact with extracellular space of the brain, cerebrospinal fluid (CSF) is the most useful biological fluid reflecting molecular events in the brain. Proteins and molecules that reflect the pathogenesis of the disease, e.g., neurodegeneration, accumulation of Abeta, hyperphosphorylation of tau protein and apoptosis may be used as biomarkers. The aim of the current manuscript is to present the most commonly used CSF biomarkers for AD as well as novel biomarkers. Three CSF biomarkers, namely total tau, phospho-tau and Abeta42, are believed to have the highest diagnostic accuracy for early AD diagnosis and the ability to predict AD development in mild cognitive impairment (MCI) patients. Moreover, other biomarkers such as soluble amyloid precursor protein (APP), apoptotic proteins, secretases and inflammatory and oxidation markers are believed to have increased future prospects.

Alzheimer's Disease as Type 3 Diabetes: Common Pathophysiological Mechanisms between Alzheimer's Disease and Type 2 Diabetes.

Globally, the incidence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) epidemics is increasing rapidly and has huge financial and emotional costs. The purpose of the current review article is to discuss the shared pathophysiological connections between AD and T2DM. Research findings are presented to underline the vital role that insulin plays in the brain's neurotransmitters, homeostasis of energy, as well as memory capacity. The findings of this review indicate the existence of a mechanistic interplay between AD pathogenesis with T2DM and, especially, disrupted insulin signaling. AD and T2DM are interlinked with insulin resistance, neuroinflammation, oxidative stress, advanced glycosylation end products (AGEs), mitochondrial dysfunction and metabolic syndrome. Beta-amyloid, tau protein and amylin can accumulate in T2DM and AD brains. Given that the T2DM patients are not routinely evaluated in terms of their cognitive status, they are rarely treated for cognitive impairment. Similarly, AD patients are not routinely evaluated for high levels of insulin or for T2DM. Studies suggesting AD as a metabolic disease caused by insulin resistance in the brain also offer strong support for the hypothesis that AD is a type 3 diabetes.

Antidiabetic Drugs in the Treatment of Alzheimer's Disease.

The public health burden of type 2 diabetes mellitus and Alzheimer's disease is steadily increasing worldwide, especially in the population of older adults. Epidemiological and clinical studies suggest a possible shared pathophysiology between the two diseases and an increased risk of AD in patients with type 2 diabetes mellitus. Therefore, in recent years, there has been a substantial interest in identifying the mechanisms of action of antidiabetic drugs and their potential use in Alzheimer's disease. Human studies in patients with mild cognitive impairment and Alzheimer's disease have shown that administration of some antidiabetic medications, such as intranasal insulin, metformin, incretins, and thiazolidinediones, can improve cognition and memory. This review aims to examine the latest evidence on antidiabetic medications as a potential candidate for the treatment of Alzheimer's disease.

The Effects of Intravitreal Administration of Antifungal Drugs on the Structure and Mechanical Properties Peripheral Blood Erythrocyte Surface in Rabbits.

BACKGROUND: Fungal infections can pose great threat to sight. Immediate treatment is usually required; antifungal agents are widely accepted and are effective in most cases. The present experimental study aims to investigate the probable effects of intravitreal injection of antifungal agents on the structure and mechanical properties of the surface of peripheral blood erythrocytes. METHODS: Nine albino New Zealand white rabbits, aged five months old, were chosen for the experiment. Solutions of micafungin, voriconazole, or balanced salt solution (BSS) were injected into the midvitreous. Animals were divided into two experimental groups and one control group. Blood sampling from an intravenous (IV) line was performed after 10 days from the last IV injection. An atomic force microscope (AFM) was used to study the structural and mechanical properties of cell surfaces. RESULTS: The analysis results showed that the parameters of the cytoskeleton's spatial organization changed insignificantly with the antifungal drug treatment. CONCLUSIONS: Our findings suggest that locally administered antifungal drugs can cause significant changes to the structure and frictional properties of the erythrocyte surface. These effects occur in the long-term period after administration of the drugs and represent a potential possibility for violation of blood supply to tissues, and the further development of negative side effects.

Pharmacogenetics and levodopa induced motor complications.

AIM: L-dopa remains the most effective symptomatic therapy for Parkinson's disease (PD) but unfortunately, its chronic use is often associated with motor complications. This review highlights the importance of pharmacogenetics in an individualised PD therapeutic approach. MATERIAL AND METHODS: review of the literature was done. RESULTS: PD patients show remarkable heterogeneity in their response to L-dopa and this profound interindividual heterogeneity suggests that there is a genetic predisposition. CONCLUSIONS: The impact of the genetic makeup of every individual on PD treatment appears to be of great importance in order to achieve not only the optimum therapeutic effect, but also with minimal side effects.

Investigation of the motor system in two siblings with Canavan's disease: a combined transcranial magnetic stimulation (TMS) - diffusion tensor imaging (DTI) study.

Canavan's disease (CD) is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to spongiform degeneration of the white matter and severe impairment of psychomotor development. We present the cases of two non-Jewish sisters with CD that have a milder and protracted clinical course compared to typical CD. MRI imaging revealed bilateral high-signal-intensity areas in the thalami and the internal capsule and MR spectroscopy showed typical findings for CD (a marked increase in N-acetylaspartate (NAA) levels). FA values of the right and left corticospinal tracts at the level of the posterior limb of the internal capsule, and the centrum semiovale were found to be significantly reduced compared to healthy controls. From a neurophysiological point of view, the peripheral motor system was normal. In contrast, cortical stimulation at maximal intensity failed to elicit facilitated or resting MEPs and silent periods (SPs) in upper and lower limbs, providing evidence for significant upper motor pathway dysfunction.

Self-report instruments of cognitive failures as screening tools for Subjective Cognitive Impairment in older adults.

BACKGROUND: The term "Subjective Cognitive Impairment (SCI)" is the most widely accepted term for cognitive complaints of otherwise apparently healthy older adults. It is presently clear that SCI might be a risk factor for the development of Mild Cognitive Impairment and dementia. As regards SCI measurement and potential diagnosis, several studies showed that SCI is a condition in which people score in the normal range on common tests but believe they experience cognitive decline. Hence, to assess the characteristic of the SCI subtle cognitive decline, self-report measures were developed to estimate "self-experience" of minimal decline in cognition seem the most appropriate tools. In this vein, the present study aimed at examining the capacity of the Greek version of two self-report instruments of the aforementioned type to detect SCI in community dwelling older adults. MATERIAL AND METHODS: The study sample consisted of 295 participants, who were allocated into four age-groups: young adults, middle-aged adults, older adults and older-old adults. The first three groups were gender and education-matched. The participants were examined via two objective tests of the Delis-Kaplan Executive Function System (D-KEFS) which is a neuropsychological battery designed to measure executive functions. In specific, they were tested via the D-KEFS Tower Test (TT) which mainly measures "planning" function, and the D-KEFS Color-Word Interference Test (C-WIT) which primarily measures "inhibition" and "switching" functions. Both tests consist of four conditions. The participants were also asked to answer to: (a) the Cognitive Failures Questionnaire (CFQ), and (b) the Prospective and Retrospective Memory Questionnaire (PRMQ), which were designed to assess subjective estimations of everyday slips of actions and cognitive failures, and episodic memory slips in everyday life, respectively. As concerns the psychometric qualities of the two questionnaires, a single-factor structure of the Greek versions of the CFQ and the PRMQ was verified in a previous study via the application of Confirmatory Factor Analysis. RESULTS: No age-group effects on CFQ score were found. Receiver Operating Characteristic (ROC) curve analyses were subsequently performed, using objective tests' scores as test variables and CFQ classification based on the 75th percentile score, as state variable. ROC curves analyses using "C-WIT conditions' 1, 2 time of completion" as test variables and CFQ classification, in older adult age-group, as state variable, showed that a CFQ score ≥47 is indicative of an early stage of objective cognitive impairment in older age. Cronbach's α values, for the Prospective and Retrospective Memory Questionnaire ranged from .89 (young adults) to .93 (older adults). No age-group effects on PRMQ score were observed. ROC curves analyses were performed, using objective measures' scores as well as CFQ score as test variables and PRMQ classification based on the 75th percentile score, as state variable. These analyses using "C-WIT conditions' 3, 4 time of completion" as well as CFQ score as test variables and PRMQ classification, in older adult age-group, as state variable, showed that a PRMQ score ≥43 is indicative of an early stage of objective cognitive impairment as well as of subjective estimations of general cognitive decline in older age. CONCLUSION: Self-report questionnaires of "everyday" cognitive and memory failures seem to be associated with specific objective tests of cognition in aging. Hence, they are useful tools for detecting early cognitive impairment at least in older adults. Their administration together with objective cognitive tasks of high difficulty could substantially help for SCI screening. Given that there is also evidence that the experience of subtle impairment in cognition is related to increased likelihood of biomarker abnormalities indicative of AD pathology, the assessment of subjective estimations is revealed as a useful primary indicator of early AD effects on cognitive functioning.

Current genetic data on depression and anxiety in Parkinson's disease patients.

Parkinson's disease (PD) is a common neurodegenerative disorder affecting about 1 % of the population over the age of 60 years. PD is characterized by a wide spectrum of symptomatology including not only motor symptoms but non-motor symptoms, as well. Depression is one of the most common non-motor manifestations, and the most frequent neuropsychiatric comorbidity in PD. Neuropsychiatric symptoms like depression and anxiety may precede the appearance of motor features, highlighting their importance in the early detection of the disease and its strategic management. This review discusses the possible genetic background of the development of these neuropsychiatric symptoms in PD patients analyzing current genetic data associated with this clinical entity.

The Genetic Landscape of Sleep Disorders in Parkinson's Disease.

Parknson's disease (PD) is the second most common neurodegenerative disease, affecting 1% of people aged over 60. PD is characterized by a wide range of motor symptoms, however the clinical spectrum of PD covers a wide range of non-motor symptoms, as well. Sleep disorders are among the most common non-motor symptoms of PD, can occur at any stage of the disease and significantly affect quality of life. These include rapid eye movement sleep behavior disorder (RBD), restless legs syndrome (RLS), excessive daytime sleepiness (EDS), insomnia, obstructive sleep apnea (OSA) and circadian rhythm disturbances. One of the main challenges in PD research is identifying individuals during the prodromal phase of the disease. Combining genetic and prodromal data may aid the early identification of individuals susceptible to PD. This review highlights current data regarding the genetic component of sleep disorders in PD patients, focusing on genes that have currently been associated with this PD co-morbidity.

The Reproductive Lifespan of Ovarian Follicle.

The functional unit within mammalian ovaries is the ovarian follicle. The development of the ovarian follicle is a lengthy process beginning from the time of embryogenesis, passing through multiple different stages of maturation. The purpose of this review is to describe the most basic events in the journey of ovarian follicle development, discussing the importance of ovarian reserve and highlighting the role of several factors that affect oocyte quality and quantity during aging including hormonal, genetic and epigenetic factors. Novel, promising anti-aging strategies are also discussed.

An Examination of the Motives for Attributing and Interpreting Deception in People with Amnestic Mild Cognitive Impairment.

The aim of the present study was to examine how a person with amnestic mild cognitive impairment perceives the phenomenon of deception. Amnestic mild cognitive impairment (aMCI) usually represents the prodromal phase of Alzheimer's disease (AD), with patients showing memory impairment but with normal activities of daily living. It was expected that aMCI patients would face difficulties in the attribution and interpretation of deceptive behavior due to deficits regarding their diagnosis. The main sample of the study consisted of 76 older adults who were patients of a daycare center diagnosed with aMCI. A sample of 55 highly educated young adults was also examined in the same experiment to qualitatively compare their performance with that of aMCI patients. Participants were assigned a scenario where a hypothetical partner (either a friend or a stranger) was engaged in a task in which the partner could lie to boost their earnings at the expense of the participant. The results showed that aMCI patients, even if they understood that something was going wrong, did not invest in interpretations of potential deception and tended to avoid searching for confirmative information related to the hypothetical lie of their partner compared to highly educated young adults. It seems that aMCI patients become somehow "innocent", and this is discussed in terms of cognitive impairment and/or socioemotional selectivity.

Association of Christian Orthodox Fasting with Sociodemographic, Anthropometric and Lifestyle Factors and Serum Biochemical Indices: A Cross-Sectional Study on Patients with Metabolic Diseases.

Christian Orthodox fasting, a type of time-restricted diet, which presents some similarities to the Mediterranean Diet, also including certain similarities with periodic vegetarianism or other time-restricted diets (e.g., intermittent diet and Ramadan fasting), may cumulatively be related to the same or even better beneficial healthy effects as these well-recognized dietary patterns. The present study aimed to explore the potential beneficial impact of Christian Orthodox fasting in patients with metabolic disorders, such as diabetes mellitus type 2, excessive obesity, hypothyroidism and osteoporosis. This was a cross-sectional study, including 135 patients with metabolic disorders (67 fasters and 68 non-fasters). The enrolled fasters had adapted Christian Orthodox fasting recommendations for at least twelve consecutive years or even from childhood. Relevant questionnaires were used to record sociodemographic, anthropometric and lifestyle data of the study population through face-to-face interviews between the enrolled individuals and qualified personnel during a non-fasting period. Christian Orthodox fasting patients showed a significantly and independently lower prevalence of overweight/obesity and abdominal obesity, which is highly associated with cardiometabolic disease risks, as well as a significantly and independently lower incidence of hypertension, including separately lower systolic and diastolic pressure, than non-fasting patients. Fasters also had a significantly and independently increased prevalence of an advanced educational level and no smoking history, as well as a lower incidence of sedentary behavior, and a trend of a correlation with reduced c-reactive protein (CRP), an indicator of inflammation, compared to non-fasters. Fasters also exhibited higher serum albumin and high-density lipoprotein (HDL) levels, as well as lower glucose levels, than non-fasters. This is one of the few cross-sectional studies demonstrating that Christian Orthodox fasting may promote metabolic health by improving several aspects of metabolic disorders, being associated with specific sociodemographic, anthropometric and lifestyle factors. Further studies conducted on larger sample sizes from different countries and different ethnicities that include Christian Orthodox fasters are recommended to evaluate the impact of long-term religious fasting effects on human health, either as a preventative factor reducing the risk of chronic diseases and especially cardiometabolic disorders or as a nutritional intervention to ameliorate symptom severity.

Stress, Anxiety, and Depression Levels among University Students: Three Years from the Beginning of the Pandemic.

BACKGROUND: Three years after the outbreak of the COVID-19 pandemic, psychological distress among college students remains increased. This study assesses stress, anxiety, and depression levels among students of the Aristotle University of Thessaloniki by the end of the third year of the pandemic (November 2022), revealing demographic characteristics and probable stressors. METHODS: A questionnaire was distributed in November 2022 via the academic students' e-mails. The evaluation was performed with the DASS21 survey tool. The correlation analysis and the effect size calculation were performed with the t-test. RESULTS: The majority of participants were undergraduates, on their first or second academic year, female students (67%), age of 18 to 21, unmarried or single (91%), and vaccinated against COVID-19 infection (83.4%). Severely increased levels of stress, anxiety, and depression (21.3%, 23.3%, and 25.1%, respectively) were measured. The normal and mild levels of stress, anxiety, and depression were 64.0%, 66.5%, and 57.2%, respectively. Female and younger students were at a higher risk of extremely severe stress, anxiety and depression prevalence (ORs up to 2.07, p-Values < 0.00001). Participants who were receiving psychological or psychiatric treatment exhibited severe stress, anxiety, and depression levels (ORs above 2.9, p-Values < 0.00001). CONCLUSIONS: Despite the undeniable withdrawal of the COVID-19 pandemic, the community of the Aristotle University of Thessaloniki presents high stress, anxiety, and depression levels, similar to those reported during the first year of the pandemic (November 2020). Stressors and risk factors were according to the reported literature and previous studies on Greek students. Academic psychological support offices should consider the students' "profile" in order to evaluate properly the potential risk for emotional and psychological distress. Evidence suggest that new technology (virtual reality, tele-psychiatry or tele-support apps and sessions) should also be implemented in universities.

Resilience in Mild Cognitive Impairment (MCI): Examining the Level and the Associations of Resilience with Subjective Wellbeing and Negative Affect in Early and Late-Stage MCI.

The current study examines the relationship between the cognitive state of participants [healthy-early mild cognitive impairment (MCI)-late MCI], some subjective wellbeing factors (positive emotions, engagement, positive relationships, meaning in life, accomplishment, and negative emotions), and negative psychological outcomes (depression, anxiety, stress), as well as psychological resilience. We expected that people with advanced MCI would perceive increased negative psychological outcomes, poorer psychological resilience, and lower levels of subjective wellbeing in contrast to early MCI and healthy participants. The study involved 30 healthy, 31 early, and 28 late MCI individuals. A series of questionnaires have been applied to assess the aforementioned constructs. To examine the hypotheses of the study, path analysis (EQS program) was applied. Results showed that early MCI persons maintain the same levels of positive emotions and feelings of accomplishment with healthy peers. Late-stage patients present those feelings in a diminished form, which adversely impacts psychological resilience. Individuals with early and late MCI exhibit negative emotions and stress that impact their resilience; however, those with early MCI experience greater stress, negative emotions, depression, and anxiety. These findings may be utilized to design psychological interventions for resilience enhancement and support brain health in elderly adults who are at risk of neurodegeneration.

R4Alz-Revised: A Tool Able to Strongly Discriminate 'Subjective Cognitive Decline' from Healthy Cognition and 'Minor Neurocognitive Disorder'.

BACKGROUND: The diagnosis of the minor neurocognitive diseases in the clinical course of dementia before the clinical symptoms' appearance is the holy grail of neuropsychological research. The R4Alz battery is a novel and valid tool that was designed to assess cognitive control in people with minor cognitive disorders. The aim of the current study is the R4Alz battery's extension (namely R4Alz-R), enhanced by the design and administration of extra episodic memory tasks, as well as extra cognitive control tasks, towards improving the overall R4Alz discriminant validity. METHODS: The study comprised 80 people: (a) 20 Healthy adults (HC), (b) 29 people with Subjective Cognitive Decline (SCD), and (c) 31 people with Mild Cognitive Impairment (MCI). The groups differed in age and educational level. RESULTS: Updating, inhibition, attention switching, and cognitive flexibility tasks discriminated SCD from HC (p ≤ 0.003). Updating, switching, cognitive flexibility, and episodic memory tasks discriminated SCD from MCI (p ≤ 0.001). All the R4Alz-R's tasks discriminated HC from MCI (p ≤ 0.001). The R4Alz-R was free of age and educational level effects. The battery discriminated perfectly SCD from HC and HC from MCI (100% sensitivity-95% specificity and 100% sensitivity-90% specificity, respectively), whilst it discriminated excellently SCD from MCI (90.3% sensitivity-82.8% specificity). CONCLUSION: SCD seems to be stage a of neurodegeneration since it can be objectively evaluated via the R4Alz-R battery, which seems to be a useful tool for early diagnosis.

Biomarkers of therapeutic efficacy in adolescents and adults with 5q spinal muscular atrophy: a systematic review.

BACKGROUND: The therapeutic landscape of spinal muscular atrophy (SMA) was dramatically transformed with the introduction of three disease-modifying therapies (DMTs). A systematic review was performed to assess available evidence regarding quantitative therapeutic biomarkers used in SMA patients older than 11 years under treatment with DMTs. METHODS: Latest literature search in MEDLINE, EMBASE, Cochrane databases and gray literature resources was performed in June 2021. Studies reporting only motor function or muscle strength scales or pulmonary function tests were excluded. Primary outcome was the change from baseline score of any serum, cerebrospinal fluid (CSF) or neurophysiologic biomarker examined. RESULTS: Database and gray literature search yielded a total of 8050 records. We identified 14 records published from 2019 until 2021 examining 18 putative serum, CSF or neurophysiologic biomarkers along with routine CSF parameters in 295 SMA nusinersen-treated type 2-4 patients older than 11 years of age. There is evidence based on real-world observational studies suggesting that serum creatinine, creatine kinase activity levels along with CSF Αß42, glial fibrillary acidic protein concentration as well as ulnar compound motor action potential amplitude and single motor unit potential amplitude changes may depict therapeutic response in this population. CONCLUSION: This systematic review explored for the first-time biomarkers used to monitor therapeutic efficacy in SMA adolescents and adults treated with DMTs. Research in this area is in its early stages, and our systematic review can facilitate selection of quantitative therapeutic biomarkers that may be used as surrogate measures of treatment efficacy in future trials. PROTOCOL REGISTRATION: PROSPERO CRD42021245516.

Cognitive Impairment in MRI-Negative Epilepsy: Relationship between Neurophysiological and Neuropsychological Measures.

BACKGROUND: Epileptic patients frequently encounter cognitive impairment. Functions that are mostly affected involve memory, attention, and executive function; however, this is mainly dependent on the location of the epileptic activity. The aim of the present study is to assess cognitive functions in MRI-negative epilepsy patients by means of neurophysiological and neuropsychological measures, as well as study the concept of transient cognitive impairment in patients with epileptiform discharges during EEG acquisition. METHODS: The patients were enrolled from an outpatient Epilepsy/Clinical Neurophysiology clinic over a time period of 6 months. The study sample comprised 20 MRI-negative epilepsy patients (mean age ± standard deviation (SD), 30.3 ± 12.56 years; age range, 16-60 years; average disease duration, 13.95 years) and 10 age-matched controls (mean age ± SD, 24.22 ± 15.39 years), who were also education-matched (p > 0.05). Patients with epileptogenic lesions were excluded from the study. Informed consent was obtained from all subjects involved in the study. Auditory ERPs and the cognitive screening tool EpiTrack were administered to all subjects. RESULTS: Latencies of P300 and slow waves were prolonged in patients compared to controls (p < 0.05). The ASM load and patients' performance in the EpiTrack maze subtest were the most significant predictors of P300 latency. A decline in the memory, attention, and speed of information processing was observed in patients with cryptogenic epilepsy compared to age-matched controls, as reflected by P300 latency and EpiTrack scores.