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Background: The driving behavior of patients with mild Alzheimer’s disease dementia (ADD) and patients with mild cognitive impairment (MCI) is frequently characterized by errors. A genetic factor affecting cognition is apolipoprotein E4 (APOE4), with carriers of APOE4 showing greater episodic memory impairment than non-carriers. However, differences in the driving performance of the two groups have not been investigated. Objective: To compare driving performance in APOE4 carriers and matched non-carriers. Methods: Fourteen APOE4 carriers and 14 non-carriers with amnestic MCI or mild ADD underwent detailed medical and neuropsychological assessment and participated in a driving simulation experiment, involving driving in moderate and high traffic volume in a rural environment. Driving measures were speed, lateral position, headway distance and their SDs, and reaction time. APOE was genotyped through plasma samples. Results: Mixed two-way ANOVAs examining traffic volume and APOE4 status showed a significant effect of traffic volume on all driving variables, but a significant effect of APOE4 on speed variability only. APOE4 carriers were less variable in their speed than non-carriers; this remained significant after a Bonferroni correction. To further examine variability in the driving performance, coefficients of variation (COV) were computed. Larger headway distance COV and smaller lateral position COV were observed in high compared to moderate traffic. APOE4 carriers had smaller speed COV compared to non-carriers. Conclusion: The lower speed variability of APOE4 carriers in the absence of neuropsychological test differences indicates reduced speed adaptations, possibly as a compensatory strategy. Simulated driving may be a sensitive method for detecting performance differences in the absence of cognitive differences.

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.

Objectives In-vehicle distraction is considered to be an important cause of road accidents. Drivers with Mild Cognitive Impairment (MCI), because of their attenuated cognitive resources, may be vulnerable to the effects of distraction; however, previous relevant research is lacking. The main objective of the current study was to explore the effect of in-vehicle distraction on the driving performance of MCI patients, by assessing their reaction time at unexpected incidents and accident probability. Methods Thirteen patients with MCI (age: 64.5 ± 7.2) and 12 cognitively intact individuals (age: 60.0 ± 7.7), all active drivers were introduced in the study. The driving simulator experiment included three distraction conditions: (a) undistracted driving, (b) conversing with passenger and (c) conversing through a hand-held mobile phone. Results The mixed ANOVA models revealed a greater effect of distraction on MCI patients. Specifically, the use of mobile phone induced a more pronounced impact on reaction time and accident probability in the group of patients, as compared to healthy controls. On the other hand, in the driving condition “conversing with passenger” the interaction effects regarding reaction time and accident probability were not significant. Notably, the aforementioned findings concerning the MCI patients in the case of the mobile phone were observed despite the effort of the drivers to apply a compensatory strategy by reducing significantly their speed in this driving condition. Conclusion Overall, the current findings indicate, for the first time, that a common driving practice, such as the use of mobile phone, may have a detrimental impact on the driving performance of individuals with MCI.

Incidental memory can be defined as the ability to acquire information unintentionally. The present study investigated incidental memory performance in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD) patients; additionally, hippocampal atrophy between groupswas examined. Twenty-nine aMCI patients (14 with hippocampal atrophy, measured by the Medial Temporal Lobe Atrophy scale), 15 mild AD patients, and 20 cognitively intact individuals underwent a detailed medical and neuropsychological assessment examining intentional memory, using the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test. Participants first took part in a driving simulator experiment, followed by an unexpected incidental memory questionnaire referring to elements related to the driving simulation. The mild AD group performed worse than the aMCI group and the control group both in incidental and intentional memory tasks, whereas the aMCI group differed significantly from the control group only in the intentional memory tasks. The incidental recognition memory task was the only measure that differed between aMCI patients with and without hippocampal atrophy. Moreover, incidental memory tasks were the only measures that correlated significantly with both left and right hippocampal atrophy. The current findings indicate that incidental memory testing may provide potentially useful information for detecting aMCI patients with greater hippocampal atrophy, who may be considered at higher risk of developing dementia due to AD.

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).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.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-2β-carbomethoxy-3β-(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.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.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.

To evaluate nonmotor symptoms in earlyThe presence of hyposmia, neuropsychiatric, dysautonomic, and sleep disturbances was assessed by standardized questionnaires and validated scales in 18 patients with A53T PD and 18 patients with tPD, matched for age, sex, and disease duration. All patients were enrolled into the Parkinson's Progression Markers Initiative study.The levodopa equivalent daily dose was higher in the A53T PD (The observed selective cognitive impairment reflecting frontal-parietal network dysfunction, together with impaired olfaction, define a set of nonmotor dysfunctions related to A53T PD. These results have implications for the prognosis of patients with A53T PD. Moreover, as the archetypal α-synucleinopathy, such results may give insights into tPD.

Previous studies indicate a negative association between depression and driving fitness in the general population. Our goal was to cover a gap in the literature and to explore the link between depressive symptoms and driving behavior in individuals with mild cognitive impairment (MCI) through the use of a driving simulator experiment.Twenty-four individuals with MCI (mean age = 67.42, SD = 7.13) and 23 cognitively healthy individuals (mean age = 65.13, SD = 7.21) were introduced in the study. A valid driving license and regular car use served as main inclusion criteria. Data collection included a neurological/neuropsychological assessment and a driving simulator evaluation. Depressive symptomatology was assessed with the Patient Health Questionnaire (PHQ-9).Significant interaction effects indicating a greater negative impact of depressive symptoms in drivers with MCI than in cognitively healthy drivers were observed in the case of various driving indexes, namely, average speed, accident risk, side bar hits, headway distance, headway distance variation, and lateral position variation. The associations between depressive symptoms and driving behavior remained significant after controlling for daytime sleepiness and cognition.Depressive symptoms could be a factor explaining why certain patients with MCI present altered driving skills. Therefore, interventions for treating the depressive symptoms of individuals with MCI could prove to be beneficial regarding their driving performance.

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative syndromes associated with several causative and susceptibility genes. Herein, we aimed to determine the incidence of the most common causative dementia genes in a cohort of 118 unrelated Greek FTD spectrum patients. We also screened for novel possible disease-associated variants in additional 21 genes associated with FTD or amyotrophic lateral sclerosis. Pathogenic or likely pathogenic variants were identified in 16 cases (13.6%). These included repeat expansions in C9orf72 and loss-of-function GRN variants, and likely pathogenic variants in TARDBP, MAPT, and PSEN1. We also identified 14 variants of unknown significance in other rarer FTD or amyotrophic lateral sclerosis genes that require further segregation and functional analysis. Our genetic screen revealed a high genetic burden in familial Greek FTD cases (30.4%), whereas only two of the sporadic cases (3.5%) carried a likely pathogenic variant. A substantial number of familial cases still remain without an obvious causal variant, suggesting the existence of other FTD genetic causes besides those currently screened in clinical routine.

Introduction The p.A53T point mutation in SNCA, the alpha-synuclein gene, has been linked to a rare dominant form of Parkinson's disease (PD). Methods Here, we describe two apparently unrelated cases of p.A53T (G209A) SNCA mutation carriers with an atypical initial manifestation and disease course. Moreover, cerebrospinal fluid (CSF) levels of tau, p-tau and amyloid Aβ42 were measured in these patients and in an additional cohort of 5 symptomatic and 2 asymptomatic p.A53T carriers without an initial manifestation of dementia. Results Both patients exhibited an early onset frontal-dysexecutive dysfunction with apathy and emotional blunting resembling frontotemporal dementia (FTD). Motor symptoms typical of Parkinson's disease appeared only later in the disease course and were less prominent than cognitive ones, which included language impairment. Autonomic dysfunction and myoclonus also emerged in a more advanced disease stage. In both patients, Brain Magnetic Resonance Imaging showed fronto-temporo-parietal atrophy, and CSF analysis showed elevated tau protein levels. In contrast, tau protein levels were normal in a cohort of 7 other p.A53T mutation carriers (5 symptomatic/2 asymptomatic). A screen of Greek patients presenting with frontotemporal dementia failed to identify any additional subjects with the p.A53T SNCA mutation. Conclusion Although cognitive decline has been recognized as a feature of the full-blown clinical picture of p.A53T related parkinsonism, a predominant frontotemporal dementia-like phenotype at presentation has not been previously described. This may represent a subtype of this disorder, with distinctive clinical, imaging and CSF biochemical characteristics, in which additional genetic or epigenetic factors may play a role.

Self-estimation of performance implies the ability to understand one's own performance with relatively objective terms. Up to date, few studies have addressed this topic in mild cognitive impairment (MCI) patients. The aim of the present study was to compare objective measures of performance with subjective perception of specific performance on cognitive tests and investigate differences in assessment between MCI patients and healthy elderly.Thirty-five participants diagnosed with MCI (women = 16, men = 19, mean age = 65.09 years ±SD = 7.81, mean education = 12.83 years ±SD = 4.32) and 35 control subjects similar in terms of age and education (women = 20, men = 15, mean age = 62.46 years ± SD = 9.35, mean education = 14.26 ± SD = 2.84) were examined with an extended battery of neuropsychological tests. After every test they were asked to self-evaluate their performance by comparing it to what they considered as average for people of their age and educational level. This self-evaluation was reported on a scale ranging from -100 to +100.Significant differences were found in the self-assessment patterns of the two groups in memory measures of verbal and visual delayed recall, visuospatial perception, and tests of attention. MCI patients overestimated their performance on every cognitive domain while control participants underestimated their performance on measures of verbal memory.The present results indicate that accuracy of self-report is not uniform across groups and functional areas. The discrepancies in the MCI patients indicate unawareness of their memory deficits, which is contradictory to subjective memory complaints as being an important component for clinical diagnosis.

Objective The aim of the current study was to investigate the impact of gender and age on incidental and intentional memory in healthy participants and to explore the strength of the association of incidental and intentional memory with attentional and executive functioning. Method A total number of 47 participants underwent a driving simulation experiment and went through detailed neuropsychological testing. Incidental memory was assessed with a questionnaire that evaluated the memorization of information related to the driving simulator task while intentional memory was assessed using the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised. Results The analysis revealed a greater impact of age on incidental as compared to intentional memory. Gender did not appear to have such an effect on either incidental or intentional memory. Finally, attentional and executive functioning were more strongly associated with incidental memory than the intentional memory measures that were utilized in the current study. Conclusions Ageing appears to affect incidental rather than intentional memory to a greater extent. In addition, attentional and executive functioning seem to play a more important role in incidental than intentional encoding and consolidation processes.