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.

Neurological Examination via Telemedicine: An Updated Review Focusing on Movement Disorders.

Patients with movement disorders such as Parkinson's disease (PD) living in remote and underserved areas often have limited access to specialized healthcare, while the feasibility and reliability of the video-based examination remains unclear. The aim of this narrative review is to examine which parts of remote neurological assessment are feasible and reliable in movement disorders. Clinical studies have demonstrated that most parts of the video-based neurological examination are feasible, even in the absence of a third party, including stance and gait-if an assistive device is not required-bradykinesia, tremor, dystonia, some ocular mobility parts, coordination, and gross muscle power and sensation assessment. Technical issues (video quality, internet connection, camera placement) might affect bradykinesia and tremor evaluation, especially in mild cases, possibly due to their rhythmic nature. Rigidity, postural instability and deep tendon reflexes cannot be remotely performed unless a trained healthcare professional is present. A modified version of incomplete Unified Parkinson's Disease Rating Scale (UPDRS)-III and a related equation lacking rigidity and pull testing items can reliably predict total UPDRS-III. UPDRS-II, -IV, Timed "Up and Go", and non-motor and quality of life scales can be administered remotely, while the remote Movement Disorder Society (MDS)-UPDRS-III requires further investigation. In conclusion, most parts of neurological examination can be performed virtually in PD, except for rigidity and postural instability, while technical issues might affect the assessment of mild bradykinesia and tremor. The combined use of wearable devices may at least partially compensate for these challenges in the future.

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.

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.

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.

Differences of apathy perfusion correlates between Alzheimer's disease and frontotemporal dementia. A 99mTc-HMPAO SPECT study with automated Brodmann areas analysis.

OBJECTIVES: To explore differences of apathy perfusion correlates between Alzheimer's disease (AD) and Frontotemporal dementia (FTD) using perfusion SPECT. METHODS: We studied 75 FTD and 66 AD patients. We evaluated apathy using Neuropsychiatric Inventory (NPI). We compared perfusion of BAs on left (L) and right (R) hemisphere in AD and FTD. RESULTS: Apathy in AD was significantly and negatively correlated with dorsolateral prefrontal cortex bilaterally, right anterior prefrontal cortex, inferior frontal cortex bilaterally, especially on the right, orbital part of inferior frontal gyrus bilaterally, left dorsal anterior cingulate cortex, right primary and secondary visual cortex, and with bilateral anterior and dorsolateral prefrontal cortex, inferior frontal cortex and orbital part of inferior frontal gyrus, bilaterally, bilateral anterior -ventral and dorsal- cingulate cortex, left posterior ventral cingulate cortex, right inferior, middle and anterior temporal gyri, entorhinal and parahippocampal cortex in FTD. CONCLUSIONS: Significant overlapping of apathy perfusion correlates between AD and FTD is seen in frontal areas and anterior cingulate. Right occipital cortex is also involved in AD, while right temporal cortex and left posterior cingulate are involved in FTD. Nuclear imaging could be a useful biomarker for revealing apathy underlying mechanisms, resulting in directed treatments.KEYPOINTSUnderlying neural networks and clinical manifestation of apathy may differ between AD and FTD.Apathy in AD is correlated with hypoperfusion in bilateral frontal areas, more prominent on the right, left anterior cingulate and right occipital cortex.Apathy in FTD is correlated with hypoperfusion in bilateral frontal areas, bilateral anterior cingulate, left posterior cingulate and right temporal cortex.Brain perfusion SPECT with automated BAs analysis and comparison with normal healthy subjects may provide significant information for apathy mechanisms in neurodegenerative disorders, affecting patients' treatment.

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.

A Novel SNCA A30G Mutation Causes Familial Parkinson's Disease.

BACKGROUND: The SNCA gene encoding α-synuclein (αSyn) is the first gene identified to cause autosomal-dominant Parkinson's disease (PD). OBJECTIVE: We report the identification of a novel heterozygous A30G mutation of the SNCA gene in familial PD and describe clinical features of affected patients, genetic findings, and functional consequences. METHODS: Whole exome sequencing was performed in the discovery family proband. Restriction digestion with Bbvl was used to screen SNCA A30G in two validation cohorts. The Greek cohort included 177 familial PD probands, 109 sporadic PD cases, and 377 neurologically healthy controls. The German cohort included 136 familial PD probands, 380 sporadic PD cases, and 116 neurologically healthy controls. We also conducted haplotype analysis using 13 common single nucleotide variants around A30G to determine the possibility of a founder effect for A30G. We then used biophysical methods to characterize A30G αSyn. RESULTS: We identified a novel SNCA A30G (GRCh37, Chr4:90756730, c.89 C>G) mutation that co-segregated with the disease in five affected individuals of three Greek families and was absent from controls. A founder effect was strongly suggested by haplotype analysis. The A30G mutation had a local effect on the intrinsically disordered structure of αSyn, slightly perturbed membrane binding, and promoted fibril formation. CONCLUSION: Based on the identification of A30G co-segregating with the disease in three families, the absence of the mutation in controls and population databases, and the observed functional effects, we propose SNCA A30G as a novel causative mutation for familial PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Evolving Causes of Rapidly Progressive Dementia: A 5-Year Comparative Study.

BACKGROUND: Rapidly progressive dementia (RPD) is a clinical syndrome developing in <1 to 2 years. Recent progress in RPD evaluation is significant, so RPD's prevalence may change over time. The aim of our new case series was to estimate the relative frequency of RPDs' causative entities, considering the recent advances in RPDs' diagnosis, and compare the results with those of our previous report. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 47 patients who were referred to Attikon University Hospital during a 5-year period for a suspected RPD. RESULTS: Neurodegenerative diseases were the most frequent causes (38%), followed by prion disease (19%) and autoimmune encephalopathy (AE, 17%). AE cases were by far more common than in our previous report, while other than AE secondary causes were significantly decreased. Mean time to dementia was 9 months in neurodegenerative diseases and 5 months in non-neurodegenerative. Main clinical findings across all patients were memory impairment (66%) and behavioral-emotional disturbances (48%). CONCLUSIONS: Neurodegenerative diseases are common causes of RPD and have a slower evolution than non-neurodegenerative. Diagnostic novelties enabled the recognition of AE, whereas more common secondary causes are probably now diagnosed in primary settings since the recognition of RPD as distinct clinical entity is continually increasing.

The impact of COVID-19 pandemic on people with mild cognitive impairment/dementia and on their caregivers.

BACKGROUND: The 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. AIMS: The 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 METHODS: Two 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. RESULTS: Results 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 period, where the available support sources were limited. DISCUSSION: The pandemic threatens to disrupt the basic routines that promote mental and physical health of both people with MCI/dementia and t heir caregivers. CONCLUSION: Further measures to protect and provide support to people who suffer and their families are needed.

Driving and Alzheimer's dementia or mild cognitive impairment: a systematic review of the existing guidelines emphasizing on the neurologist's role.

BACKGROUND: Driving is a complex task requiring the integrity and the cooperation of cognition, motor, and somatosensory skills, all of which are impacted by neurological diseases. OBJECTIVE: Identification of neurologist's role when assessing fitness to drive of cognitively impaired individuals. METHODS: We performed a systematic review of the guidelines/recommendations (G/Rs) regarding the evaluation of driving fitness of patients with mild cognitive impairment (MCI) and/or dementia. Emphasis was put on the neurological and neuropsychological aspects of the evaluation. RESULTS: Eighteen G/Rs were included in the review (9 national guidelines, 5 recommendation papers, 3 consensus statements, and 1 position paper). All G/Rs referred to drivers with dementia and 9/18 referred to drivers with MCI. A common approach among G/Rs is the initial trichotomization of patients in safe to drive, unsafe to drive, and undetermined cases, which are referred to a second-line evaluator. First-line evaluators are general practitioners in 10/18 G/Rs; second-line evaluators are neurologists in 7/18 G/Rs. Specific neuropsychological tests are proposed in 11/18 G/Rs and relative cut-off values in 7/18. The most commonly used tests are the MMSE, TMT, and CDT. A thorough neurological examination is proposed in only 1/18 G/R. CONCLUSION: Although extensive multi-disciplinary research has provided useful information for driving behavior of cognitively impaired individuals, we are still far from a widely accepted approach of driving ability evaluation in this increasing population. A comprehensive assessment from a multi-disciplinary team in which the neurologist plays a critical role seems to be required, although this has not yet been implemented in any G/Rs.

Physical Training In-Game Metrics for Cognitive Assessment: Evidence from Extended Trials with the Fitforall Exergaming Platform.

Conventional clinical cognitive assessment has its limitations, as evidenced by the environmental shortcomings of various neuropsychological tests conducted away from an older person's everyday environment. Recent research activities have focused on transferring screening tests to computerized forms, as well as on developing short screening tests for screening large populations for cognitive impairment. The purpose of this study was to present an exergaming platform, which was widely trialed (116 participants) to collect in-game metrics (built-in game performance measures). The potential correlation between in-game metrics and cognition was investigated in-depth by scrutinizing different in-game metrics. The predictive value of high-resolution monitoring games was assessed by correlating it with classical neuropsychological tests; the area under the curve (AUC) in the receiver operating characteristic (ROC) analysis was calculated to determine the sensitivity and specificity of the method for detecting mild cognitive impairment (MCI). Classification accuracy was calculated to be 73.53% when distinguishing between MCI and normal subjects, and 70.69% when subjects with mild dementia were also involved. The results revealed evidence that careful design of serious games, with respect to in-game metrics, could potentially contribute to the early and unobtrusive detection of cognitive decline.

Predictors of accidents in people with mild cognitive impairment, mild dementia due to Alzheimer's disease and healthy controls in simulated driving.

OBJECTIVES: To examine the driving variables that predict accident probability in mild dementia due to Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy older control drivers in simulated driving. To compare the three groups in mean performance and in frequency of scores exceeding 1.5 SD from the mean. METHODS/DESIGN: Participants were 37 drivers with MCI, 16 drivers with AD, and 21 control drivers over the age of 52. Driving measures were derived from four rural driving conditions: moderate traffic without and with distraction and high traffic without and with distraction. The measures were z-transformed based on the performance of 90 control drivers of different ages. Two unexpected incidents occurred per condition, requiring the sudden breaking to avoid an accident. RESULTS: Drivers with AD showed significantly lower average speed, speed variability, greater headway distance, headway variability and average reaction time (RT) than control drivers. Drivers with MCI showed significantly lower average speed, greater headway distance and average RT than control drivers in the two conditions of distraction. No differences were found in accident probability. Drivers with AD had more deviant scores than both control drivers and drivers with MCI in most comparisons. Predictors of accident probability were average RT, speed variability and lateral position variability but MCI and AD status were not significant predictors in any of the regression models. CONCLUSIONS: Despite significant differences in performance, drivers with MCI and AD did not differ in accident probability from control drivers. An individualized approach of examining individual driving performance is recommended.

The Neural Correlates of Impaired Self-Monitoring Among Individuals With Neurodegenerative Dementias.

OBJECTIVE: 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.

Defining Neuropsychiatric Inventory scale differences across frontotemporal dementia syndromes.

AIM: The aim of this study was to assess the ability of Neuropsychiatric Inventory (NPI) scale profiles to differentiate between distinct frontotemporal dementia (FTD) subtypes. METHODS: The NPI was used to assess 311 older patients who had been clinically diagnosed with FTD. FTD subtypes included behavioural variant FTD (bvFTD, n = 121), primary progressive aphasia (semantic variant (n = 69), non-fluent agrammatic variant (n = 31), and logopenic variant (n = 0)), FTD-motor neuron disease (n = 4), progressive supranuclear palsy (n = 43), and corticobasal syndrome (n = 43). Total NPI score and scores for each NPI item were correlated across the distinct FTD subtypes. RESULTS: Patients with bvFTD showed significantly greater impairment on their total NPI score than patients with corticobasal syndrome (P < 0.001), non-fluent agrammatic variant primary progressive aphasia (P < 0.001), progressive supranuclear palsy (P = 0.002), and semantic variant primary progressive aphasia (P = 0.010). Aggressiveness, euphoria, apathy, disinhibition, irritability, aberrant motor behaviours, and appetite disturbance were significantly higher in bvFTD than in the other subgroups. The lowest NPI scores were generally shown among those with CBS. However, NPI total and specific item values overlapped among the subtypes. CONCLUSIONS: Patients with bvFTD showed significantly greater neuropsychiatric dysfunction than those with the other FTD subtypes, as measured by the NPI scale. In contrast, patients with corticobasal syndrome had a comparatively healthier profile. Therefore, differential diagnosis among the FTD subtypes may be guided by the NPI, although the subtype is unlikely to be confirmed on the basis of NPI alone.

123I-FP-CIT SPECT [(123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] Imaging in a p.A53T α-synuclein Parkinson's disease cohort versus Parkinson's disease.

BACKGROUND: The p.A53T point mutation in the α-synuclein gene (SNCA) is a rare but highly relevant cause of autosomal dominant Parkinson's disease (PD). OBJECTIVES: The objective of this study was to assess striatal dopaminergic denervation in a cohort of symptomatic carriers of the p.A53T SNCA mutation as compared to PD patients. METHODS: Data from the Parkinson's Progression Markers Initiative database of 11 symptomatic p.A53T SNCA mutation carriers who underwent 123I-FP-CIT SPECT [(123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging at our site were compared with those of 33 age-, sex-, and disease duration-matched PD patients. RESULTS: The p.A53T mutation carriers had significantly lower caudate nucleus binding ratio both contralaterally and ipsilaterally to the most affected side (P = .002 and P = .006) and a decreased contralateral caudate/putamen signal ratio (P = .007) as compared to PD. A similar degree of striatal asymmetry was observed in both subgroups. No correlation between scores in neuropsychological tests and caudate nucleus dopaminergic denervation could be demonstrated. CONCLUSIONS: PD patients harboring the p.A53T SNCA mutation show evidence of a more severe nigrostriatal denervation, especially evident in the caudate nucleus. The lack of significant differences in the putaminal binding ratios may reflect a floor effect or a true preferential targeting of the caudate terminals in p.A53T SNCA-associated PD. © 2018 International Parkinson and Movement Disorder Society.

Self-awareness of Driving Ability in the Healthy Elderly and Patients With Mild Cognitive Impairment (MCI).

INTRODUCTION: According to latest research, a percentage of cognitively impaired drivers fail to recognize their areas of weakness and overestimate their driving abilities. METHODS: Twenty-seven individuals with amnestic mild cognitive impairment (MCI) and 26 healthy elderly drivers participated in a driving simulator study. After the driving assessment, participants were asked to self-evaluate their performance in comparison with what they considered as average for people of similar age and educational level. RESULTS: According to the applied mixed analysis of variance model, the MCI patients presented increased difficulties in estimating their driving performance to a greater extent in the rural environment in comparison with the urban condition. DISCUSSION: Our findings suggest that the ability of MCI patients to evaluate their driving performance accurately seems to be enhanced or compromised, depending on the number of cues available in their environment, suggesting that providing feedback may improve their metacognitive abilities.

Testamentary Capacity Assessment: Legal, Medical, and Neuropsychological Issues.

INTRODUCTION: The increase in the aging population and the number of patients with dementia led to the research in older adults' capacity assessment over the last 3 decades. Many cases of contested wills occur due to lack of testamentary capacity (TC), especially in cases of dementia. AIM: Purpose of the present study was to overview the legal, medical, and neuropsychological aspects of TC as well as the instruments used for TC assessment. FINDINGS: The testator/testatrix with intact TC has realistic perception of his or her property value, lack of psychopathology affecting contact with reality, and intact intention of how and to whom he or she will dispose his or her assets. It is frequent for the health practitioners to serve as "gold standards assessors" by examining an individual's ability to make a valid will and giving evidence to the court to support or not a will contest. The TC assessment is a complex process of clinical and legal practice requiring usually a variety of methods, that is, interviews, evaluation of clinical records, and administration of neuropsychological instruments. CONCLUSION: The evaluation of TC is a multidimensional process that integrates both the legal and medical field, requiring a collaborative approach to its definition and assessment.