Stella Fragkiadaki

Frontotemporal dementia as the presenting phenotype of p.A53T mutation carriers in the alpha-synuclein gene

INTRODUCTION The p.A53T point mutation in SNCA, the alpha-synuclein gene, has been linked to a rare dominant form of Parkinsons 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 Parkinsons 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-awareness of cognitive efficiency: Differences between healthy elderly and patients with mild cognitive impairment (MCI)

ABSTRACT Introduction: 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. Method: 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. Results: 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. Conclusions: 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.

Incidental and Intentional Memory: Their Relation with Attention and Executive Functions

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.

Selective cognitive impairment and hyposmia in p.A53T SNCA PD vs typical PD

Objective To evaluate nonmotor symptoms in early SNCA/p.A53T Parkinson disease (PD) (A53T PD) compared to typical PD (tPD). Methods The 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 Parkinsons Progression Markers Initiative study. Results The levodopa equivalent daily dose was higher in the A53T PD (p = 0.018) group vs the tPD group. Scores on the University of Pennsylvania Smell Identification Test (p = 0.001), Benton Judgement of Line Orientation test (p = 0.001), Letter Number Sequencing Test (p = 0.002), and phonemic verbal fluency (p = 0.002) were lower in the A53T PD group vs the tPD group. In contrast, overall cognition, verbal memory, and semantic fluency were similar between groups. Conclusion 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.

Driving in mild cognitive impairment: The role of depressive symptoms

ABSTRACT Objectives: 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. Methods: 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). Results: 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. Conclusions: 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.

THE ASSESSMENT OF INCIDENTAL AND INTENTIONAL MEMORY IN PATIENTS WITH AMNESTIC MILD COGNITIVE IMPAIRMENT (AMCI) AND PATIENTS WITH DEPRESSION

represents an entity with specific executive (Delrieu et al, 2016) and motor impairments. Recently, two subtypes have been established: potentially-reversible and reversible cognitive-frailty (Ruan et al, 2015), related to mild cognitive impairment and subjective cognitive decline respectively. Recommendation for cognitive assessment includes screening (i.e. clock-drawing) and neuropsychological tests (i.e. verbal learning, processing speed and verbal fluency tasks). Conclusions:The conceptual and operational definition of Cognitive Frailty present implications for the study of neuropsychological profiles; the study of vascular, inflammatory, nutritional, and metabolic mechanisms involved; the role of the cognitive reserve construct; and its potential reversibility. Implications for cognitive screening and preventive interventions are discussed. Funding: This work was supported by the Xunta de Galicia, FrailNet network IN607C 2016/08.

SELF-EVALUATION OF DRIVING ABILITY THROUGH A DRIVING SIMULATOR EXPERIMENT: DIFFERENCES BETWEEN PATIENTS WITH MILD COGNITIVE IMPAIRMENT (MCI) AND HEALTHY ELDERLY DRIVERS

assumed without an adequate analysis, especially in Old Adults (OA). Among the “weak” stationarity tests, the Priestley-Subba Rao (PSR) test calculates a “local” spectra that is “valid” only for punctual moments in time. A series of “smoothed” frequency filters give information of the time the local spectra is calculated. In here, weak REM sleep stationarity by the PSR test was compared to that from Wakefulness (W) and Non-REM (NREM) sleep. Methods: 8 Old Adults (OA) (age: 67.6 6 5.7; education: 8.8 6 2.6) without depression neither anxiety and with intact daily living activities were selected. Also, evaluations with the Mini-Mental State Examination (MMSE, 28.1 6 1.8) and a one night polysomnography were performed. 30 second epochs were classified according to the AASM and every epoch of W, NREM and REM sleep was subjected to PSR tests. Percentages of stationary epochs were obtained with respect to the total number of epochs of each stage and Student t-tests were used to compare them. Results: The PSR effectively showed different proportions of stationarity according to the classification of stages in each subject. In Figure 1, in one OA, epochs with stationarity are shown in black and the classification of REM sleep is shown in green. Clearly, a lower proportion of stationarity was found in REM sleep vs the other stages. These differences reached significance in F7, Fp2, LOG and ROG (p < 0.05, Figure 2). Conclusions: In OA, REM sleep showed lower proportions of epochs with stationarity vs. W and NREM sleep at anterior areas, a result that could be explained by the tonic and phasic REM sleep. When stationarity measurements are planned, it is recommended to differentiate anterior from lateral and posterior areas.