Exploring the Impact of Age of Onset of Mild Cognitive Impairment on the Profile of Cognitive and Psychiatric Symptoms.

The present study aims to explore the differences in the manifestation of cognitive decline and psychiatric symptoms across the different ages of MCI onset: early onset (EOMCI: <65 years old), middle onset (MOMCI: 65-75 years old), and late onset (LOMCI: >75 years old). It was hypothesized that individuals with EOMCI will preserve their cognitive functions to a greater extent as compared to individuals with LOMCI, even after adjusting the cognitive performance for age and education through the use of published Greek norms. The level of cognitive decline concerning MOMCI was evaluated for extracting more precise conclusions regarding the impact of the age of onset on the patterns of MCI symptomatology. The analyses of data were conducted in a Greek population of individuals with MCI, who were consecutive visitors of the Outpatient Memory Clinic of Nestor Alzheimer's Centre in Athens, Greece. The sample consisted of 297 participants who fulfilled the following inclusion criteria: MCI diagnosis based on Petersen's criteria, Greek mother language, and absence of a psychiatric history or chronic and incurable organic disease. The overall results support the presence of a cognitive advantage of the EOMCI group compared to the LOMCI group. In the MOMCI group, cognitive performance displayed a tendency to remain intermediate compared to the other two groups. Nonetheless, significant differences were observed when this group was compared with the LOMCI group. The current findings indicate that the age of onset should be taken under consideration in the neuropsychological assessment of individuals with MCI. The specific parameters could have implications in terms of prognosis as well as the design and implementation of tailored interventions.

The Differential Role of Executive Apathy in Alzheimer's Disease Dementia, Mild Cognitive Impairment and Healthy Cognitive Ageing.

The objective of the present work was to compare the levels of executive, emotional, and initiation apathy in individuals with mild cognitive impairment (MCI), mild Alzheimer's disease dementia (ADD), and cognitively intact healthy controls (HCs). Fifty-two patients with mild ADD, 40 individuals with MCI, and 37 cognitively intact individuals were included in the current study. The participants were consecutive visitors to the Outpatient Memory Clinic of "Nestor" Alzheimer's Center. The symptoms of apathy were measured with the dimensional apathy scale. Analyses showed that ADD patients had significantly higher degrees of executive, emotional, initiation, and overall apathy compared with both the MCI group and the HCs. Additionally, a significant difference was observed in the dimension of executive apathy between individuals with MCI and the HCs. In conclusion, the dimension of executive apathy was the most sensitive measure regarding the differentiation of individuals with mild ADD or MCI and HCs. Hence, detailed evaluation of executive apathy in older individuals referred to a memory clinic may provide useful information contributing to their diagnostic categorization and to the differentiation between neurocognitive disorders and healthy cognitive ageing.

Frontotemporal dementia spectrum: first genetic screen in a Greek cohort.

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.

Exploring the Profile of Incidental Memory in Patients with Amnestic Mild Cognitive Impairment and Mild Alzheimer's Disease.

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.

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.

Mild Cognitive Impairment and driving: Does in-vehicle distraction affect driving performance?

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 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.

Driving in mild cognitive impairment: The role of depressive symptoms.

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.

Self-awareness of cognitive efficiency: Differences between healthy elderly and patients with mild cognitive impairment (MCI).

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.

Amnesia in frontotemporal dementia: shedding light on the Geneva historical data.

Recent accumulated evidence indicates that episodic memory impairments could be part of the initial clinical expression of frontotemporal dementia (FTD). An early study on this issue was carried out by Constantinidis and colleagues in 1974, but it was subsequently overlooked for a long period of time. The scope of the present research was: (a) to explore the presence of early episodic memory impairments in the entire population of neuropathologically confirmed FTD patients from the Geneva brain collection; and (b) to expand the present insight on the association between the initial symptomatology and various characteristics, namely gender, age at onset, disease duration, and presence of Pick body neuropathology. A careful review of the records of 50 FTD patients hospitalized at the Department of Psychiatry of the Bel-Air Hospital, Geneva, Switzerland, from 1929 to 1999, was conducted. Further in-depth neuropathological analysis with novel immunohistological methods was carried out in 37 of the cases. The data showed that memory impairments were the first clinical symptom in several of the patients. In addition, this specific phenotypic expression of FTD was associated with the female gender, advanced age, and positive Pick body neuropathology. The current findings give the opportunity to historically vindicate the early work of Constantinidis and colleagues. In addition, the novel observations about the association of episodic memory impairments with the female gender and positive Pick body neuropathology add to the existing knowledge about this phenotypic expression of FTD.

Prenatal tobacco smoke exposure, risk of schizophrenia, and severity of positive/negative symptoms.

Prenatal exposure to cigarette smoke causes chronic fetal hypoxia, dysregulation of endocrine equilibrium, and disruption of fetal neurodevelopment associated with brain malfunction, all of which potentially could induce vulnerability to schizophrenia. A total of 212 schizophrenia patients aged 14-30years, and 212 matched controls were studied. Prenatal tobacco smoke exposure of the schizophrenia patients was compared to that of the normal controls by applying logistic regression analysis and controlling for several confounding factors. The outcomes of interest were comparison of the frequency of maternal and paternal smoking between patients and controls, as well as the severity of positive and negative symptoms between the offspring of smoking and nonsmoking parents. Among the mothers of schizophrenia patients and controls, 92 (43.4%) and 46 (21.7%) smoked, respectively. Maternal smoking during pregnancy had a significant unique contribution on increasing the risk for development of schizophrenia (p=0.001), and a greater severity of negative symptoms (p=0.023). Paternal smoking did not have a significant effect on the risk of schizophrenia, or severity of negative symptoms. The findings suggest that maternal smoking during pregnancy puts offspring at an increased risk for later schizophrenia, with increased severity of negative symptoms. Given the wide practice of smoking during pregnancy, fetal exposure to tobacco smoke could be a major preventable neurodevelopmental factor that increases vulnerability to schizophrenia.

Investigation of the link between higher order cognitive functions and handedness.

The study aimed to investigate the hypothesis that in high-functioning individuals the left-handedness phenotype facilitates the performance of executive-related tasks that engage the right hemisphere. The Trail-Making Test and Letter-Number Sequencing, previously indicated to engage the right hemisphere, were applied on 47 right-handers and 50 left-handers. There was a significant effect of handedness on both measures and an interaction effect of gender and handedness on the Trail-Making Test. The findings are considered to support the view that greater engagement of right-hemispheric resources facilitates the performance of higher order functions that orchestrate cognition, such as mental flexibility, inhibitory control, and working memory operations.

Community psychological stressor-induced secondary sex ratio decline after a seismic sequence in the Greek island of Zakynthos.

The secondary sex ratio (the ratio of boys to girls at birth) may demonstrate a decline following community stress-inducing major destructive events. This study aims to investigate whether or not moderate adverse life events, in conjunction with endogenous psychological characteristics, can induce sufficient community stress to affect the sex ratio. From April 3rd to May 8th 2006 a moderate sized earthquake sequence occurred offshore the Greek island of Zakynthos, which had been hit by a destructive earthquake half a century earlier. The monthly sex ratio after the earthquake sequence was estimated and compared with that of previous and following years. Eleven months after the onset of the earthquakes the sex ratio fell to 1.000, and during the next two months (March and April) it declined further to 0.612. The sex ratio one year before its decline was 1.158 and over a total 6-year period, 3 years before and 3 years after the sequence, it was 1.063; the March-April decline in male births is significant (OR=0.53, 95% CI=0.32-0.86, p=0.013, and OR=0.57, 95% CI=0.36-0.91, p=0.023, respectively). Also, the number of boys relative to girls in March-April 2007 was significantly lower than during the same months 3 years before and after the sequence (OR=0.50, 95% CI=0.31-0.82, p=0.007). The findings suggest that basic biological characteristics, such as the sex ratio, can be affected by psychological stressors interwoven with the pertaining psychology of the population.

Sex differences in prepsychotic "prodromal" symptomatology and its association with Positive and Negative Syndrome Scale active phase psychopathology in male and female patients.

BACKGROUND: A wide spectrum of prodromal symptoms has been reported, but their association with the severity of the active phase psychopathology in relationship to sex is unknown. METHOD: Seventy-three (47 male) Diganostic and Statistical Manual (DSM) schizophrenia patients were subjected to the structured clinical interview for Positive and Negative Syndrome Scale (PANSS). Prodromal symptoms were recorded retrospectively after psychotic phase had subsided. RESULTS: Thirty-eight prodromal symptoms were identified. All symptoms appeared in both sexes. However, there was a significantly greater frequency of 3 symptoms (odd beliefs/magical thinking, over elaborate speech, hyperacusia) in female patients and of 2 symptoms (marked peculiar behavior, aggressiveness) in male patients. In the female patients, 9 symptoms were associated with an increased risk for severe total and components of the PANSS psychopathology in the psychotic phase; 2 symptoms were associated with a mild negative subscale psychopathology. In the male patients, 6 symptoms were associated with the severity of the PANSS psychopathology; 5 carried an increase risk for severe and 1 was associated with mild psychopathology. Also, the risk for severe PANSS positive, general, and total psychopathology increased with the increasing number of total and less specific symptoms in the female but not in the male patients. CONCLUSIONS: Sex differences in schizophrenia are extended into the prepsychotic stage. Also, the presence of certain prodromal symptoms, different in men and women, and the number of symptoms in female patients are associated with the severity of the psychotic phase psychopathology. Evaluation of early therapeutic interventions in prodromal phase should consider sex and spectrum of prodromal symptoms.

Relationship of "prodromal" symptoms with severity and type of psychopathology in the active phase of schizophrenia.

BACKGROUND: Both retrospective and prospective studies have identified a broad spectrum of "prodromal" symptoms, but their relationship to those of frank psychosis remains largely unexplored. METHOD: In 73 successive hospitalized patients with schizophrenia in the first or second psychotic episode and with duration of illness 3 years or less from the onset of psychosis, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, Axis I diagnoses were made. In addition, within the first 5 days from the psychotic episode's onset, symptom severity was assessed with the Positive and Negative Syndrome Scale (PANSS). RESULTS: Stepwise regression analyses showed that 8 prodromal symptoms carried an increased risk for high total PANSS and the components of the PANSS scores, independently of sex; 1 symptom was associated with mild psychopathology. However, the categories of negative- and positive-disorganization prodromal symptoms were not associated with the corresponding PANSS components. Similar findings were observed in the nonparanoid patients, whereas in the paranoid, only 2 nonspecific symptoms were associated with high PANSS psychopathology. In addition, there were significant associations between number of prodromal symptoms and total PANSS and the subscales positive and general scores in the patients with the nonparanoid subtypes, but there were not such associations in those with the paranoid. CONCLUSIONS: Several prodromal symptoms, as well as the number of symptoms, are associated with the severity of the psychopathology of frank psychosis. In the nonparanoid subtypes there is a continuance in the transition from the prepsychotic to the psychotic stage, whereas in the paranoid, the transition appears to be disrupted.

Effect of handedness on the Stroop Colour Word Task.

Handedness is associated with cerebral organisation, but its relationship with cognition remains unclear. Since the Stroop task is believed to measure aspects of executive control, this study aims to investigate the effect of handedness on Stroop interference. We used the Stroop task with 90 young adults with university education, of whom 47 (23 males) were right-handed and 43 (21 males) were left-handed. Main dependent variables were Stroop baseline (SB), Stroop incongruent (SI), and the proportional derivative Stroop reduction (SR) [SR=(SB - SI)/SB×100%] (Bugg, Delosh, Davalos, & Davis, 2007; Graf, Uttl, &Tuokko, 1995) scores. The analysis revealed that SI is significantly affected by both handedness and the interaction of sex×handedness, whereas SR is only affected by handedness. After controlling for the effect of SB on SI, only the effect of handedness remained statistically significant [F(1, 83) = 6.44, p=.013]. Post-hoc comparisons showed that left-handed females performed significantly better than right-handed females on both SI (p=.003) and SR (p=.007). The data suggest that handedness is associated with cognitive function alterations, which lead to a smaller Stroop interference of left-handers irrespectively of sex, an effect that is more pronounced in the female subpopulation.

Effect of initiation-inhibition and handedness on the patterns of the P50 event-related potential component: a low resolution electromagnetic tomography study.

BACKGROUND: Recent research recognizes the association between handedness, linguistic processes and cerebral networks subserving executive functioning, but the nature of this association remains unclear. Since the P50 event related potential (ERP) is considered to reflect thalamocortical processes in association with working memory (WM) operation the present study focuses on P50 patterns elicited during the performance of a linguistic related executive functioning test in right- and left-handers. METHODS: In 64 young adults with a high educational level (33 left-handed) the P50 event-related potential was recorded while performing the initiation and inhibition condition of a modified version of the Hayling Sentence Completion test adjusted to induce WM. The manual preference of the participants was evaluated with the use of the Edinburgh Handedness Inventory (EHI). RESULTS: P50 showed greater amplitudes in left- than in right-handers, mainly in frontal leads, in the initiation condition. Reduced amplitudes in inhibition compared to initiation condition were observed in left-handers. Low Resolution Electromagnetic Tomography (LORETA) analysis showed lower frontal lobe activation in the inhibition than in the initiation condition in both right- and left-handers. Also, LORETA yielded that right-handers exhibited greater activation in the inhibition condition than left-handers. Additionally, LORETA showed assymetrical hemispheric activation patterns in right-handers, in contrast to symmetrical patterns observed in left-handers. Higher P50 amplitudes were recorded in right-hemisphere of right-handers in the initiation condition. CONCLUSION: Brain activation, especially the one closely related to thalamocortical function, elicited during WM operation involving initiation and inhibition processes appears to be related to handedness.