Multimodal Approach to Neurocognitive Function in People Living with HIV in the cART Era: A Comprehensive Review.

Combination antiretroviral treatment (cART) has revolutionized the management of human immunodeficiency virus (HIV) and has markedly improved the disease burden and life expectancy of people living with HIV. HIV enters the central nervous system (CNS) early in the course of infection, establishes latency, and produces a pro-inflammatory milieu that may affect cognitive functions, even in the cART era. Whereas severe forms of neurocognitive impairment (NCI) such as HIV-associated dementia have declined over the last decades, milder forms have become more prevalent, are commonly multifactorial, and are associated with comorbidity burdens, mental health, cART neurotoxicity, and ageing. Since 2007, the Frascati criteria have been used to characterize and classify HIV-associated neurocognitive disorders (HAND) into three stages, namely asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). These criteria are based on a comprehensive neuropsychological assessment that presupposes the availability of validated, demographically adjusted, and normative population data. Novel neuroimaging modalities and biomarkers have been proposed in order to complement NCI assessments, elucidate neuropathogenic mechanisms, and support HIV-associated NCI diagnosis, monitoring, and prognosis. By integrating neuropsychological assessments with biomarkers and neuroimaging into a holistic care approach, clinicians can enhance diagnostic accuracy, prognosis, and patient outcomes. This review interrogates the value of these modes of assessment and proposes a unified approach to NCI diagnosis.

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.

Parkinson's Disease and Driving Fitness: A Systematic Review of the Existing Guidelines.

BACKGROUND: Motor/nonmotor symptomatology and antiparkinsonian drugs deteriorate the driving ability of Parkinson's disease (PD) patients. OBJECTIVES: Treating neurologists are frequently asked to evaluate driving fitness of their patients and provide evidence-based consultation. Although several guidelines have been published, the exact procedure along with the neurologist's role in this procedure remains obscure. METHODS: We systematically reviewed the existing guidelines, regarding driving fitness evaluation of PD patients. We searched MEDLINE and Google Scholar and identified 109 articles. After specified inclusion criteria were applied, 15 articles were included (nine national guidelines, five recommendation papers, and one consensus statement). RESULTS: The treating physician is proposed as the initial evaluator in 8 of 15 articles (neurologist in 2 articles) and may refer patients for a second-line evaluation. The evaluation should include motor, cognitive, and visual assessment (proposed in 15, 13, and 8 articles, respectively). Specific motor tests are proposed in eight articles (cutoff values in four), whereas specific neuropsychological and visual tests are proposed in seven articles each (cutoff values in four and three articles, respectively). Conditional licenses are proposed in 11 of 15 articles, to facilitate driving for PD patients. We summarized our findings on a graphic of the procedure for driving fitness evaluation of PD patients. CONCLUSIONS: Neurological aspects of driving fitness evaluation of PD patients are recognized in most of the guidelines. Motor, neuropsychological, visual, and sleep assessment and medication review are key components. Clear-cut instructions regarding motor, neuropsychological, and visual tests and relative cutoff values are lacking. Conditional licenses and periodical reevaluation of driving fitness are important safety measures.

Effect of a 36-Week Supervised Exercise Training Program on Physical and Cognitive Function in Older Patients With Dementia.

BACKGROUND/AIM: To investigate the effects of an exercise training program on physical and cognitive function in older patients with dementia. PATIENTS AND METHODS: Thirty-eight patients with early-middle dementia (31 females and seven males), aged 80.6±6.9 years, residents in an Elderly Care Unit, either completed a 36-week structured exercise program (Intervention Group, IG; n=19), or received the usual medical care (Control Group, CG; n=19). Before and after the 36-week intervention, cognitive function was evaluated in both groups by Mini-Mental State Examination (MMSE) and depression by Geriatric Depression Scale (GDS); physical function was assessed using handgrip test, Timed Up to Go (TUG), Berg Balance Scale (BBS) and Chair-Stand Test (CST), and daily living functionality by Functional Rating Scale for Symptoms of Dementia (FRSSD). RESULTS: As a result of exercise intervention, participants scored better in all functional and cognitive test assessments compared to the control group, as reflected by absolute and relative (%) differences in all metrics after the 36-week exercise program (p<0.001). CONCLUSION: A 36-week supervised exercise training program was found to result in significant improvements in physical and cognitive function of elderly patients in early to middle stages of dementia at an Elderly Care Unit. The promising results of this study shed more light on the adaptability of elderly patients with early and mild dementia to long-term exercise training and verified the feasibility of applying such programs in this clinical population.

Comprehensive Evaluation of Psychotic Features and Their Clinical Correlates in Early Parkinson's Disease.

BACKGROUND: Some reports suggest that psychotic features may occur in the early stages of Parkinson's disease (PD), but sensitive tools have not been utilized. OBJECTIVE: The aim was to evaluate the presence of psychotic symptoms using detailed scales and to assess the association with clinical characteristics. METHODS: Healthy controls and patients within three years of PD onset were recruited. Participants were examined for psychotic symptoms using two different instruments: the Comprehensive Assessment of At-Risk Mental States (CAARMS) and a 10 question PD specific psychosis severity scale (10PDQ). In the PD group, medication use, motor and non-motor symptoms were documented. RESULTS: Based on CAARMS and 10PDQ scales, psychotic features were present in 39% (27/70) of patients and 4% (3/74) of controls. The prevalence of passage hallucinations and illusions was significantly higher in PD compared to the control group. The presence of PD-associated psychotic features was not significantly affected by medication, motor severity or global cognitive status. Higher prevalence of overall non-motor manifestations, REM sleep behavior disorder (RBD) and depressive symptoms was significantly associated with the manifestation of psychotic features in PD [(adjusted OR:1.3; 95% CI:1.1-1.6; p = 0.003), (adjusted OR:1.3; 95% CI:1.0-1.6; p = 0.023), and (adjusted OR:1.2; 95% CI:1.0-1.4;p = 0.026)]. CONCLUSIONS: Psychotic phenomena mainly of minor nature are highly common in early PD. Cumulative non-motor symptoms, RBD and depressive features are associated with the presence of psychotic symptoms in this non-demented, early-stage PD population. More studies are needed to clarify the mechanisms that contribute to the onset of psychotic features in early PD.

Jumping to conclusions bias, psychosis and impulsivity in early stages of Parkinson's disease.

OBJECTIVES: The aim was to explore the correlations between Jumping to Conclusions (JtC) tendency and neuropsychiatric features in patients with early Parkinson's disease (PD). BACKGROUND: According to few reports, PD patients with impulsive-compulsive behaviors (ICBs) are prone to working memory difficulties including JtC bias. The correlation of psychotic features and JtC tendency remains still unclear. METHODS: Healthy controls and patients within 3 years of PD onset were recruited. Participants were examined for psychotic symptoms using a 10 question PD-specific psychosis severity scale. JtC was measured by a probalistic reasoning scenario (beads task). In PD group, medication use, motor and non-motor symptoms were documented. Impulsivity was evaluated using the Questionnaire for Impulsive-Compulsive Disorders in PD (QUIP). RESULTS: The prevalence of JtC bias was 9% (6/70) in healthy individuals, compared to 32% (22/68) of PD group [p = 0.001]. No association was detected between the presence of JtC tendency and PD-associated psychosis (p = 0.216). Patients with JtC had shorter duration of PD, more tremor-dominant PD subtype and higher QUIP scores, regardless of the dopaminergic therapy (p = 0.043, p = 0.015, p = 0.007, respectively). A trend towards attention and inhibition control deficit was noticed in JtC patients. CONCLUSIONS: We found a high prevalence of JtC bias in early, cognitively intact PD population and a potential link between subthreshold ICBs and poor performance on beads task. Additional studies are needed to confirm our results and elaborate on the mechanisms that correlate impulsivity with JtC tendency, which are likely to be different from those mediating psychotic features in early PD.

Double Trouble: Association of Malignant Melanoma with Sporadic and Genetic Forms of Parkinson's Disease and Asymptomatic Carriers of Related Genes: A Brief Report.

Introduction: Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson's disease (PD). Shared molecular mechanisms have been proposed to be implicated in this relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes. Methods: Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history. Results: In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%). Conclusions: We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.

The Effects of a Single Session of a Rhythmic Movement Program on Selected Biopsychological Parameters in PD Patients: A Methodological Approach.

The aim of the present study is to examine the acute effects of a specially designed musicokinetic (MSK) program for patients with Parkinson's disease (PD) on (a) anxiety levels, (b) select kinematic and kinetic parameters, and (c) frontal cortex hemodynamic responses, during gait initiation and steady-state walking. Methods: This is a blind cross-over randomized control trial (RCT) in which 13 volunteers with PD will attend a 45 min MSK program under the following conditions: (a) a synchronous learning format and (b) an asynchronous remote video-based format. Changes in gait biomechanics and frontal cortex hemodynamic responses will be examined using a 10-camera 3D motion analysis (Vicon T-series, Oxford, UK), and a functional near-infrared spectroscopy (f-NIRS-Portalite, Artinis NL) system, respectively, while anxiety levels will be evaluated using the Hamilton Anxiety Rating Scale. Expected results: Guided by the rules of music, where periodicity is distinct, our specially designed MSK program may eventually be beneficial in improving motor difficulties and, hence, reducing anxiety. The combined implementation of f-NIRS in parallel with 3D gait analysis has yet to be evaluated in Parkinsonian patients following a MSK intervention. It is expected that the aforementioned intervention, through better rhythmicity, may improve the automatization of motor control, gait kinematics, and kinetics-supported by decreased frontal cortex hemodynamic activity-which may be linked to reduced anxiety levels.

Pharmacological and Non-Pharmacological Treatments for Depression in Parkinson's Disease: An Updated Review.

Depression represents one of the most common non-motor disorders in Parkinson's disease (PD) and it has been related to worse life quality, higher levels of disability, and cognitive impairment, thereby majorly affecting not only the patients but also their caregivers. Available pharmacological therapeutic options for depression in PD mainly include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants; meanwhile, agents acting on dopaminergic pathways used for motor symptoms, such as levodopa, dopaminergic agonists, and monoamine oxidase B (MAO-B) inhibitors, may also provide beneficial antidepressant effects. Recently, there is a growing interest in non-pharmacological interventions, including cognitive behavioral therapy; physical exercise, including dance and mind-body exercises, such as yoga, tai chi, and qigong; acupuncture; therapeutic massage; music therapy; active therapy; repetitive transcranial magnetic stimulation (rTMS); and electroconvulsive therapy (ECT) for refractory cases. However, the optimal treatment approach for PD depression is uncertain, its management may be challenging, and definite guidelines are also lacking. It is still unclear which of these interventions is the most appropriate and for which PD stage under which circumstances. Herein, we aim to provide an updated comprehensive review of both pharmacological and non-pharmacological treatments for depression in PD, focusing on recent clinical trials, systematic reviews, and meta-analyses. Finally, we discuss the pharmacological agents that are currently under investigation at a clinical level, as well as future approaches based on the pathophysiological mechanisms underlying the onset of depression in PD.

Serum Uric Acid as a Putative Biomarker in Prodromal Parkinson's Disease: Longitudinal Data from the PPMI Study.

BACKGROUND: The role of blood uric acid as a biomarker in symptomatic motor PD has been increasingly established in the literature. OBJECTIVE: Our present study assessed the role of serum uric acid as a putative biomarker in a prodromal PD cohort [REM Sleep Behavior disorder (RBD) and Hyposmia] followed longitudinally. METHODS: Longitudinal 5-year serum uric acid measurement data of 39 RBD patients and 26 Hyposmia patients with an abnormal DATSCAN imaging were downloaded from the Parkinson's Progression Markers Initiative database. These cohorts were compared with 423 de novo PD patients and 196 healthy controls enrolled in the same study. RESULTS: After adjusting for age, sex, body mass index, and concomitant disorders (hypertension/gout), baseline and longitudinal serum uric acid levels were higher in the RBD subgroup as compared to the established PD cohort (p = 0.004 and p = 0.001). (Baseline RBD 6.07±1.6 vs. Baseline PD 5.35±1.3 mg/dL and Year-5 RBD 5.7±1.3 vs. Year-5 PD 5.26±1.33). This was also true for longitudinal measurements in the Hyposmic subgroup (p = 0.008) (Baseline Hyposmic 5.7±1.6 vs. PD 5.35±1.3 mg/dL and Year-5 Hyposmic 5.58±1.6 vs. PD 5.26±1.33). CONCLUSION: Our results indicate that serum uric acid levels are higher in prodromal PD subjects with ongoing dopaminergic degeneration compared to those with manifest PD. These data indicate that the well-established decrease in the levels of serum uric acid occurs with the transition from prodromal to clinical PD. Whether the higher levels of serum uric acid observed in prodromal PD may provide protection against conversion to full-blown clinical PD will require further study.

Genetic Insights into the Molecular Pathophysiology of Depression in Parkinson's Disease.

Background and Objectives: Parkinson's disease (PD) is a clinically heterogeneous disorder with poorly understood pathological contributing factors. Depression presents one of the most frequent non-motor PD manifestations, and several genetic polymorphisms have been suggested that could affect the depression risk in PD. Therefore, in this review we have collected recent studies addressing the role of genetic factors in the development of depression in PD, aiming to gain insights into its molecular pathobiology and enable the future development of targeted and effective treatment strategies. Materials and Methods: we have searched PubMed and Scopus databases for peer-reviewed research articles published in English (pre-clinical and clinical studies as well as relevant reviews and meta-analyses) investigating the genetic architecture and pathophysiology of PD depression. Results: in particular, polymorphisms in genes related to the serotoninergic pathway (sodium-dependent serotonin transporter gene, SLC6A4, tryptophan hydrolase-2 gene, TPH2), dopamine metabolism and neurotransmission (dopamine receptor D3 gene, DRD3, aldehyde dehydrogenase 2 gene, ALDH2), neurotrophic factors (brain-derived neurotrophic factor gene, BDNF), endocannabinoid system (cannabinoid receptor gene, CNR1), circadian rhythm (thyrotroph embryonic factor gene, TEF), the sodium-dependent neutral amino acid transporter B(0)AT2 gene, SLC6A15), and PARK16 genetic locus were detected as altering susceptibility to depression among PD patients. However, polymorphisms in the dopamine transporter gene (SLC6A3), monoamine oxidase A (MAOA) and B (MAOB) genes, catechol-O-methyltransferase gene (COMT), CRY1, and CRY2 have not been related to PD depression. Conclusions: the specific mechanisms underlying the potential role of genetic diversity in PD depression are still under investigation, however, there is evidence that they may involve neurotransmitter imbalance, mitochondrial impairment, oxidative stress, and neuroinflammation, as well as the dysregulation of neurotrophic factors and their downstream signaling pathways.

Imaging Markers for Normal Pressure Hydrocephalus: An Overview.

Idiopathic bormal pressure hydrocephalus (iNPH) is a neurological syndrome that clinically presents with Hakim's triad, namely cognitive impairment, gait disturbances, and urinary incontinence. The fact that iNPH is potentially reversible makes its accurate and early diagnosis of paramount importance. Its main imaging characteristic is the dilation of the brain's ventricular system and the imaging parameters are also included in its diagnostic criteria along with clinical data. There is a variety of different modalities used and a great number of imaging markers that have been described while assessing iNPH patients. The present literature review attempts to describe the most important of these imaging markers and to shed some light on their role in diagnosis, differential diagnosis, and possibly prognosis of this potentially reversible neurological syndrome.

Exploring the Role of ACE2 as a Connecting Link between COVID-19 and Parkinson's Disease.

Coronavirus disease 2019 (COVID-19) is frequently accompanied by neurological manifestations such as headache, delirium, and epileptic seizures, whereas ageusia and anosmia may appear before respiratory symptoms. Among the various neurological COVID-19-related comorbidities, Parkinson's disease (PD) has gained increasing attention. Some cases of PD disease have been linked to COVID-19, and both motor and non-motor symptoms in Parkinson's disease patients frequently worsen following SARS-CoV-2 infection. Although it is still unclear whether PD increases the susceptibility to SARS-CoV-2 infection or whether COVID-19 increases the risk of or unmasks future cases of PD, emerging evidence sheds more light on the molecular mechanisms underlying the relationship between these two diseases. Among them, angiotensin-converting enzyme 2 (ACE2), a significant component of the renin-angiotensin system (RAS), seems to play a pivotal role. ACE2 is required for the entry of SARS-CoV-2 to the human host cells, and ACE2 dysregulation is implicated in the severity of COVID-19-related acute respiratory distress syndrome (ARDS). ACE2 imbalance is implicated in core shared pathophysiological mechanisms between PD and COVID-19, including aberrant inflammatory responses, oxidative stress, mitochondrial dysfunction, and immune dysregulation. ACE2 may also be implicated in alpha-synuclein-induced dopaminergic degeneration, gut-brain axis dysregulation, blood-brain axis disruption, autonomic dysfunction, depression, anxiety, and hyposmia, which are key features of PD.

How Well Did the Healthcare System Respond to the Healthcare Needs of Older People with and without Dementia during the COVID-19 Pandemic? The Perception of Healthcare Providers and Older People from the SI4CARE Project in the ADRION Region.

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 and BiH. According to our results, countries from the Adrion/Ionian regions faced significant challenges to adjust to the special needs of the older people during the COVID-19 pandemic, which was possibly due to limited accessibility opportunities to healthcare facilities. These results highlight the need for the development of alternative ways of providing medical assistance and supervision when in-person care is not possible.

The nonverbal BriefScreen: A cognitive screening method for patients with limited language and motor abilities.

Dementia and significant cognitive decline are frequent sequelae of stroke, but are difficult to evaluate when aphasia and/or motor impairment are present. The linguistic and motor requirements of commonly employed screening tests render them problematic for use post-stroke. The present study examines the validity of the Nonverbal BriefScreen, a brief screening method with limited verbal and motor requirements, in groups of patients with known cognitive impairment using the MMSE as a gold standard. Participants were 137 healthy middle aged and older community dwellers, 21 patients with MCI/early dementia and 35 patients with different types of dementia. The sensitivity and specificity of the Nonverbal BriefScreen were calculated for various cutoff scores, with the MMSE as comparison. The Nonverbal BriefScreen was effective in discriminating between healthy controls and patients with dementia, as well as between healthy controls and all patients, with areas under the ROC curve similar to that of the MMSE. ROC analyses with a smaller sample of 35 age-matched healthy controls showed adequate discriminant ability to detect cognitive impairment. The Nonverbal BriefScreen was shown to be a valid method for screening for cognitive impairment that could be employed as a screening method for patients with limited language.

Perceptions of Patients, Caregivers, and Healthcare Professionals toward Telemedicine Use for Cognitive and Movement Disorders in the Aegean Islands, Greece: A Pilot Study of the SI4CARE European Project.

BACKGROUND: Patients with neurodegenerative diseases who live in remote areas often have limited access to specialized healthcare, and telemedicine represents a useful solution. The aim of this study was to investigate the perceptions toward the use of a specialized-tertiary telemedicine service of patients with cognitive and movement disorders, caregivers, and local healthcare professionals (HPs) in the Aegean Islands. METHODS: Data were derived from the "Specialized Outpatient Clinic of Memory, Dementia and Parkinson's disease through the National Telemedicine Network", March 2021-March 2023. The survey included 10 questions (5-point Likert scale). RESULTS: We received 64 questionnaires (25 patients, 18 caregivers, 21 HPs). Most participants positively perceived all aspects of telemedicine, including comfort (mean ± standard deviation: patients 4.5 ± 0.9, caregivers: 4.8 ± 0.5, HPs: 4.6 ± 0.7), access to specialized care (4.7 ± 0.6, 4.7 ± 0.5, 4.9 ± 0.4), number of transportations (4.6 ± 0.8, 4.6 ± 0.9, 4.8 ± 0.5), adequacy of follow-up (4.6 ± 0.7, 4.4 ± 0.8, 4.2 ± 0.7), future telemedicine selection (4.8 ± 0.4, 4.8 ± 0.4, 4.6 ± 0.6), perceived reliable medical assessment (4.7 ± 0.5, 4.6 ± 0.6, 4.3 ± 0.6), information delivery (4.7 ± 0.6, 4.6 ± 0.5, 4.4 ± 0.9), health status improvement (4.6 ± 0.7, 4.6 ± 0.6, 4.0 ± 0.7), cost (4.6 ± 1, 4.6 ± 1, 5.0 ± 0.2), and general satisfaction (4.8 ± 0.4, 4.7 ± 0.5, 4.5 ± 0.6). The commonest recommendations were more frequent visits, medical specialties, and dissemination of information. CONCLUSIONS: The positive perception of participants highlights the value of telemedicine for specialized healthcare for neurodegenerative disorders, especially in remote areas.

Cerebrospinal Fluid Biomarkers in iNPH: A Narrative Review.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological syndrome characterized by the clinical triad of gait disorder, cognitive impairment and urinary incontinence. It has attracted interest because of the possible reversibility of symptoms, especially with timely treatment. The main pathophysiological theory is based on a vicious circle of disruption in circulation of cerebrospinal fluid (CSF) that leads to the deceleration of its absorption. Data regarding CSF biomarkers in iNPH are contradictory and no definite CSF biomarker profile has been recognized as in Alzheimer's disease (AD), which often co-exists with iNPH. In this narrative review, we investigated the literature regarding CSF biomarkers in iNPH, both the established biomarkers total tau protein (t-tau), phosphorylated tau protein (p-tau) and amyloid peptide with 42 amino acids (Aß42), and other molecules, which are being investigated as emerging biomarkers. The majority of studies demonstrate differences in CSF concentrations of Aß42 and tau-proteins (t-tau and p-tau) among iNPH patients, healthy individuals and patients with AD and vascular dementia. iNPH patients present with lower CSF Aß42 and p-tau concentrations than healthy individuals and lower t-tau and p-tau concentrations than AD patients. This could prove helpful for improving diagnosis, differential diagnosis and possibly prognosis of iNPH patients.

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.

Silent Pauses and Speech Indices as Biomarkers for Primary Progressive Aphasia.

Background and Objectives: Recent studies highlight the importance of investigating biomarkers for diagnosing and classifying patients with primary progressive aphasia (PPA). Even though there is ongoing research on pathophysiological indices in this field, the use of behavioral variables, and especially speech-derived factors, has drawn little attention in the relevant literature. The present study aims to investigate the possible utility of speech-derived indices, particularly silent pauses, as biomarkers for primary progressive aphasia (PPA). Materials and Methods: We recruited 22 PPA patients and 17 healthy controls, from whom we obtained speech samples based on two elicitation tasks, i.e., cookie theft picture description (CTP) and the patients' personal narration of the disease onset and course. Results: Four main indices were derived from these speech samples: speech rate, articulation rate, pause frequency, and pause duration. In order to investigate whether these indices could be used to discriminate between the four groups of participants (healthy individuals and the three patient subgroups corresponding to the three variants of PPA), we conducted three sets of analyses: a series of ANOVAs, two principal component analyses (PCAs), and two hierarchical cluster analyses (HCAs). The ANOVAs revealed significant differences between the four subgroups for all four variables, with the CTP results being more robust. The subsequent PCAs and HCAs were in accordance with the initial statistical comparisons, revealing that the speech-derived indices for CTP provided a clearer classification and were especially useful for distinguishing the non-fluent variant from healthy participants as well as from the two other PPA taxonomic categories. Conclusions: In sum, we argue that speech-derived indices, and especially silent pauses, could be used as complementary biomarkers to efficiently discriminate between PPA and healthy speakers, as well as between the three variants of the disease.