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We report a patient with a chronic subdural/epidural hematoma superimposed to a large arachnoid cyst occupying the left frontotemporal region. Both were discovered accidentally because of a trigeminal neuralgia and concomitant subjective memory complaints. Patient's sudden selective audioverbal memory impairment probably links to a primary cortical tone deregulation and expressed through deficits of arousal-mediating structures subtly impacted by the hematoma's progression. This case illustrates that in early-onset asymmetrical brain damage (usually left), language, audioverbal memory in particular, should not always come to dominate intact hemisphere function. A

Background Primary progressive aphasia (PPA) is a clinical syndrome that is characterized by progressive deterioration of language while other cognitive domains remain relatively intact. The extent to which print exposure and cortical volume atrophy jointly influence picture naming and general language ability in individuals with PPA remains underexplored. Objective To investigate the language performance of individuals with the nonfluent variant of primary progressive aphasia (nfvPPA) and to explore the impact of print exposure and cortical volume atrophy on their language ability. Method We compared 14 Greek individuals with nfvPPA and similar age, education, disease duration, and cognitive ability with age-, gender- and education-matched Greek controls on picture naming and on language tasks of the Boston Diagnostic Aphasia Examination-Short Form, including oral word reading, word and sentence repetition, complex ideational material, and reading comprehension. The effects of print exposure and left-hemisphere cortical volume on the individuals' language performance were estimated through stepwise regression models. Results The language performance of the individuals with nfvPPA was affected by print exposure and cortical volume atrophy. Picture naming and word reading were affected by print exposure. The highest contributions of cortical volume atrophy were found for the repetition, complex ideational material, and reading comprehension tasks. Conclusion Print exposure and cortical volume atrophy may help explain variability in the language performance of nfvPPA individuals with similar age, education, disease duration, and cognitive ability.

Objective The aim of the present study was to investigate the efficacy and feasibility of a telerehabilitation program in multi-domain amnestic Mild Cognitive Impairment (md-aMCI). The study sample consisted of 30 patients with md-aMCI and aged 60–80 years. Methods The participants were randomly divided into two groups. The Training Group (TG), which received cognitive training by using the RehaCom software as well as paper-pencil language training and the Control Group (CG) which received standard clinical care (e.g., psychotherapy or/and physiotherapy). Duration of the telerehabilitation intervention was 15 weeks (twice a week for 60 min/session). Results Our results revealed that the neuropsychological performance of the TG group after the telerehabilitation intervention improved on a statistically significant level on the domains of delayed and working memory, confrontation naming, verbal fluency, and global cognition. Comparison between the TG and CG revealed a significant impact of the telerehabilitation program on the domains of memory (delay and working) and language (naming and verbal fluency) as well as global cognition performance. Conclusion The findings of the study are promising in that the telerehabilitation intervention appears to be a useful method in improving or stabilizing cognitive decline in md-aMCI individuals and was a particularly effective alternative approach during the period of the pandemic lockdown. Specifically, the beneficial impact of the telerehabilitation intervention on episodic memory (which is one of the first domains to show impairment in md-aMCI patients) provides us with hope and evidence that these types of interventions may be applied with similar success using face-to-face interventions.

Introduction Short cognitive screening instruments (CSIs) are widely used to stratify patients presenting with cognitive symptoms. The Quick Mild Cognitive Impairment (Qmci) screen is a new, brief ( Methods Consecutive patients aged ≥55 years presenting with cognitive complaints were recruited from two outpatient clinics in Greece. All patients completed the Qmci-Gr and SMMSE and underwent an independent detailed neuropsychological assessment to determine a diagnostic classification. Results In total, 140 patients, median age 75 years, were included; 30 with mild dementia (median SMMSE 23/30), 76 with MCI and 34 with subjective memory complaints (SMC) but normal cognition. The Qmci-Gr had similar accuracy in differentiating SMC from cognitive impairment (MCI & mild dementia) compared with SMMSE, area under the curve (AUC) of 0.84 versus 0.79, respectively; while accuracy was higher for the Qmci-Gr, this finding was not significantly different, (p = .19). Similarly, the Qmci-Gr had similar accuracy in separating SMC from MCI, AUC of 0.79 versus 0.73 (p = .23). Conclusions The Qmci-Gr compared favorably with the SMMSE. Further research with larger samples and comparison with other instruments such as the Montreal Cognitive Assessment is needed to confirm these findings but given its established brevity, it may be a better choice in busy clinical practice in Greece.

Rehabilitation is “a set of interventions designed to optimize functioning and reduce disability in individuals with health conditions in interaction with their environment”, according to the recent report from the World Health Organization (WHO), released in January 2023 [...]

The purpose of the present study was to explore whether Computer-Based Cognitive Training (C-BCT) versus Paper-Pencil Cognitive Training (P-PCT) is more beneficial in improving cognitive and language deficits in Greek patients living with Alzheimer’s disease (pwAD). Twenty pwAD were assigned to two groups: (a) the C-BCT group, receiving a computer-based cognitive training program using the RehaCom software, and (b) the P-PCT group, which received cognitive training using paper and pencil. The cognitive training programs lasted 15 weeks and were administered twice a week for approximately one hour per session. The analyses of each group’s baseline versus endpoint performance demonstrated that the P-PCT group improved on delayed memory, verbal fluency, attention, processing speed, executive function, general cognitive ability, and activities of daily living. In contrast, the C-BCT group improved on memory (delayed and working), naming, and processing speed. Comparisons between the two groups (C-BCT vs. P-PCT) revealed that both methods had significant effects on patients’ cognition, with the P-PCT method transferring the primary cognitive benefits to real-life activities. Our findings indicate that both methods are beneficial in attenuating cognitive and language deficits in pwAD. The need for large-scale neurobehavioral interventions to further clarify this issue, however, remains a priority.

The purpose of the present study was to explore the effects of computer-based multidomain cognitive training program on Greek patients with Mild Cognitive Impairment (MCI). Forty-six patients with MCI were randomly divided into two groups; (a) the training group, which received a computer-based multidomain cognitive training program with the use of the RehaCom software and (b) the control group, which underwent standard-clinical care. The duration of the computer-based training program was 15 weeks, administered twice a week for approximately one hour per session. Analysis of the baseline versus endpoint performance of each group demonstrated that in the control group delayed memory and executive function had deteriorated over the observation period of 15 weeks, while improvement was observed in the training group's performance on delayed memory, word recognition, Boston Naming Test (BNT), Clock Drawing Test (CDT), Semantic Fluency (SF), Trail Making Test-A (TMT-A) and Trail Making Test-B (TMT-B). Comparison between the two groups presented asignificant effect of the intervention for most cognitive domains. These findings are promising for the development of training methods designed to delay cognitive decline in patients with MCI, which is considered to be the prodromal stage of Alzheimer's Disease (AD).

This study investigated the effects of hierarchical cognitive training using the categorization program (CP), designed initially for adults with cognitive deficits associated with traumatic brain injury (TBI). Fifty-eight participants were included: a group of fifteen young adults with TBI (ages 18-48), another group of fifteen noninjured young adults (ages 18-50), and two groups of adults over 60 randomly assigned into the experimental group (n=14) or the control group (n=14). Following neuropsychological testing, the two young adult groups and the experimental older adult group received the CP training for 10-12 weeks. The CP training consisted of 8 levels targeting concept formation, object categorization, and decision-making abilities. Two CP tests (administered before and after the training) and three probe tasks (administered at specified intervals during the training) assessed skills relating to categorization. All treated groups showed significant improvement in their categorization performance, although younger participants (with or without TBI) demonstrated greater gains. Gains on the categorization measures were maintained by a subgroup of older adults up to four months posttraining. Implications of these findings in terms of adult cognitive learning and directions for future research on adult cognitive rehabilitation and cognitive stimulation programs are discussed.

Non-invasive brain stimulation (NIBS) has emerged as one of the methods implemented in stroke rehabilitation. Cerebellar stimulation has gained research interest as an alternative strategy to cortical stimulation, based on the role of the cerebellum and corticocerebellar tracts in different motor and cognitive functions. This review investigates the role of the cerebellum in motor and cognitive rehabilitation following cerebral stroke using NIBS techniques combined with other therapies (e.g., speech or physical therapy). Fifteen randomized clinical trials were included. The majority of the literature findings point towards the cerebellum as a promising neurostimulation target following stroke of the cerebral cortex. Findings concern mostly rehabilitation of gait and balance, where cathodal transcranial direct current stimulation (tDCS) and intermittent theta-burst stimulation (iTBS) of the contralesional cerebellar hemisphere produce, in the presented clinical sample, improved performance and plasticity changes in the corticocerebellar network, combined with other rehabilitation methods. Data regarding aphasia rehabilitation are scarce, with right cerebellar tDCS exercising some impact in individual linguistic functions combined with language therapy. Based on recent data concerning cerebellar functions and corticocerebellar networks, along with the development of clinical protocols regarding non-invasive cerebellar (NICS) application, the cerebellum can prove a crucial intervention target in rehabilitation following stroke.

Depersonalization is a dissociative disorder associated to a profound disruption of self-awareness in the form of emotional numbing and feelings of disembodiment. The salient feature of depersonalization is a breakdown in the familiarity of one's psychological and somatic self (and surroundings when derealization is also present), in spite of being aware of the unreality of the change. At an early stage of research it was realized that people inclined to dissociation find it harder to tolerate discontinuity in perceptual environments, possibly due to a rigid perceptual attitude. Consequently, perceptual discontinuity experienced during momentary immersion into a VE would be expected to increase symptoms of dissociation among individuals prone to develop them. It has been put forward that a tendency toward immersion or absorption, linking to imaginative processes underlying the dissociative experience, significantly relates to the level of change in virtual reality-induced dissociative symptoms. Consequently, it has been implied that increased tolerability of perceptual discontinuities and a more flexible perceptual attitude in people suffering depersonalization/derealization disorder may be of help. We propose the use of adaptive immersive virtual environments to the treatment of depersonalization. In particular, we propose that implementation of biofeedback electrical stimulation to detect somato-sensory processing bias may contribute to selectively targeting deranged neurocognitive processing components, and as an indirect consequence promote, to some extent, the diagnostic process. Psychophysiological approaches may be of help in the treatment of depersonalization via additional series of afferent inputs - virtual reality (VR) stimuli - to alter the receptive fields of the affected proprioceptive systems and reorganize them. The aim of this paper is to stimulate future research towards the development of potential virtual rehabilitation programs based on biofeedback, electrical stimulation and concurrent measurement of galvanic skin response and EEG targeting selective somatosensory stimulation in patients with depersonalization. Our research hypotheses might constitute a starting point for the development of new treatment tools for depersonalization in particular and depersonalization/derealization disorder in general.

To compare neuropsychological function in juvenile myoclonic epilepsy (JME) and frontal lobe epilepsy (FLE) since frontal circuitry is involved in both conditions. By drawing on previously theory-guided hypotheses and findings, a particular emphasis is placed on the way different cognitive-pathophysiological mechanisms act upon to produce frontal dysfunction in JME (frontal-executive and attention-related problems: vigilance, reaction times, processing speed, and response inhibition) and in FLE (reflecting the coproduct of the functional deficit zone), respectively.A total of 16 patients with JME, 34 patients with FLE, and 48 normal controls, all matched for age and education, were administered a comprehensive battery of tests to assess frontal-executive functions, as well as attention, memory, and learning domains. Participants did not take medications other than antiepileptics or have a psychiatric history.Patients with FLE overall showed worse neuropsychological performance compared to both JME and HCs. With respect to JME, patients with FLE did significantly worse in measures of verbal and nonverbal executive function, short-term-, and long-term- auditory-verbal memory and learning, immediate and delayed episodic recall, visual attention and motor function, visuo-motor coordination and psychomotor speed, speed of visual information processing, and vocabulary. Patients with JME performed significantly worse compared to FLE only in associative semantic processing, while the former outperformed all groups in vocabulary, visuomotor coordination, and psychomotor speed.We suggest that selective impairments of visual- and mostly auditory-speed of information processing, vigilance, and response inhibition may represent a salient neuropsychological feature in JME. These findings suggest the existence of an aberrantly working executive-attention system, secondary to pathological reticulo-thalamo-cortical dynamics. Contrariwise, cortically (frontal and extra-frontal) and subcortically induced malfunction in FLE is determined by the functional deficit zone i.e., the ensemble of cortical and subcortical areas that are functionally abnormal between seizures.

BACKGROUND Sustained cognitive testing is used to detect cognitive fatigability and is often considered a substitute for subjective cognitive fatigue (CF). However, the relationship between cognitive fatigability and subjective CF in people with multiple sclerosis (PwMS) remains undetermined. OBJECTIVE To explore potential associations between fatigability induced by sustained cognitive testing and subjective CF in PwMS. METHODS We gave 120 PwMS and 60 demographically matched, healthy individuals the Beck Depression Inventory-FastScreen (BDI-FS) to measure mood and the Modified Fatigue Impact Scale to measure CF. In addition, we used the Quotient ADHD Test, a sustained attention test, to measure cognitive fatigability. We also explored potential correlations between the individuals' performance on the sustained attention test and thalamic volume using recent MRI scans. RESULTS Forty-one (34.2%) of the PwMS exhibited cognitive fatigability. These 41 were found to be significantly older (P=0.006), had been diagnosed with the disease for longer (P=0.03), had higher scores (P

We investigated: (i) the cognitive performance of type 2 diabetes mellitus (T2DM) patients compared to healthy control participants and (ii) the Health-related Quality of life (HRQOL) of type 2 diabetics with neuropsychological deficits.We conducted a prospective study in (N = 44) T2DM patients and (N = 28) demographically matched healthy controls. All participants were assessed with a flexible comprehensive neuropsychological battery of tests that have been standardized in Greece and found to be sensitive in detecting cognitive deficits in type 2 diabetics. They were additionally assessed on measures of general intelligence, general mental state, and depression. They were also administered the WHO QOL-BREF self-report questionnaire to evaluate perceived health-related quality of life.Groups were well matched on baseline demographic characteristics and estimated premorbid intelligence. The groups did not differ on general mental state but varied in the encoding of verbal material, total verbal learning, delayed recall of verbal information, mental information processing speed, phonological and semantic verbal fluency and executive functions, set-shifting. Glycosylated hemoglobin levels and an interaction of age, education, and premorbid intelligence were the most important predictors of domain-specific neuropsychological performance. T2DM patients with deficits in verbal learning, executive functions, set-shifting, and semantic verbal fluency, had significantly lower QOL in the domains of psychological and environmental health, social relationships, and general health, respectively.T2DM patients have cognitive deficits on several domains compared to healthy participants. Domain specific neuropsychological deficits in middle aged T2DM patients have a significant impact on HRQOL.

Primary progressive aphasia (PPA) is a clinical syndrome that is characterized by progressive deterioration of language while other cognitive domains remain relatively intact. The extent to which print exposure and cortical volume atrophy jointly influence picture naming and general language ability in individuals with PPA remains underexplored.To investigate the language performance of individuals with the nonfluent variant of primary progressive aphasia (nfvPPA) and to explore the impact of print exposure and cortical volume atrophy on their language ability.We compared 14 Greek individuals with nfvPPA and similar age, education, disease duration, and cognitive ability with age-, gender- and education-matched Greek controls on picture naming and on language tasks of the Boston Diagnostic Aphasia Examination-Short Form, including oral word reading, word and sentence repetition, complex ideational material, and reading comprehension. The effects of print exposure and left-hemisphere cortical volume on the individuals' language performance were estimated through stepwise regression models.The language performance of the individuals with nfvPPA was affected by print exposure and cortical volume atrophy. Picture naming and word reading were affected by print exposure. The highest contributions of cortical volume atrophy were found for the repetition, complex ideational material, and reading comprehension tasks.Print exposure and cortical volume atrophy may help explain variability in the language performance of nfvPPA individuals with similar age, education, disease duration, and cognitive ability.

Cognitive impairment is common in multiple sclerosis, but the brain MRI correlates in relapsing remitting multiple sclerosis remain controversial. The current study aimed to investigate whether cognitive decline can be predicted by global and/or regional brain atrophy.Sixty-three patients with relapsing remitting multiple sclerosis (36 men, mean age 39.9 ± 9.4 years old, mean EDSS 1.4 ± 1.2, mean disease duration 4.9 ± 4.3 years) and 46 healthy controls (21 men, mean age 37.5 ± 10.8 years old) were included. Demographic data were obtained, and a longitudinal neuropsychological and global and regional MRI brain volume assessment was performed.The patients performed worse than controls in most neuropsychological tests at baseline. The percentage of patients with clinically meaningful cognitive decline ranged from only 0% to 7.9%. Statistically significant volume reduction was found for all MRI measures except for the left accumbens nucleus. Whole or regional brain atrophy ranged from -0.02% to -0.25%, with subcortical structures showing the largest atrophy rates. A total of 22.2% to 93.7% patients showed atrophy across the brain structures assessed volumetrically.It was regional rather than whole-brain changes that significantly predicted cognitive decline for the patients in the tasks that tested processing speed, visuo-spatial and inhibition skills. The overall data suggest that the progression of cognitive impairment in relapsing remitting multiple sclerosis as captured by conventional neuropsychological testing is the tip of the iceberg of neurodegenerative sequelae in the disease. Also, regional volumetric changes are better than whole-brain atrophy at predicting cognitive dysfunction.

The Multiple Sclerosis Neuropsychological Questionnaire is a brief screening questionnaire for the assessment of everyday neuropsychological competence of patients with Multiple Sclerosis. The aim of the present study was to examine psychometric properties of the Greek version of the instrument. One hundred and three MS patients and 60 informants participated in the present study and completed the questionnaire. From the initial patient sample, 51 participants completed broadly used neuropsychological tests and measures estimating cognitive failures and depression. Moreover, after a six-month interval the MSNQ was administered to 58 patients from the initial sample in order to explore test-retest reliability. Cronbach's α was 0.92 and 0.93 for patient and informant forms, respectively. The patient form was correlated significantly with measures of cognitive failures and depression. Low correlations were found between the informant form and performance on cognitive tests. In regard to the patient form, significant correlation was observed between repeated administrations and, psychometrically, the three-factor structure was preferable than the one-factor structure. The present study confirms the already established pattern of correlations among the two MSNQ forms, neuropsychological test performance and depression measurements. Additional research is needed in order to define a cut-off score for the MSNQ-I providing further information about the diagnostic interpretability of the instrument.

About half of patients with multiple sclerosis exhibit cognitive impairment which negatively affects their quality of life. The assessment of cognitive function in routine clinical practice is still undervalued, although various tools have been proposed for this reason. In this article, we describe the potential benefits of implementing cognitive assessment tools in routine follow -ups of MS patients. Early detection of changes in cognitive performance may provide evidence of disease activity, could unmask depression or medication side-effects and provide suitable candidates for cognitive rehabilitation. Since apathy and cognitive deficiencies are common presenting symptoms in Progressive Multifocal Leukoencephalopathy, we discuss the utility of frequent monitoring of mental status in multiple sclerosis patients at increased risk. In addition, we propose a relevant algorithm aiming to incorporate a systematic evaluation of cognitive function in every day clinical practice in multiple sclerosis.

Alzheimer’s disease and vascular dementia account for the majority of cases of cognitive decline in elderly people. These two main forms of dementia, under which various subtypes fall, are often overlapping and, in some cases, definitive diagnosis may only be possible post-mortem. This has implications for the quality of care and the design of individualized interventions for these patients. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality used to visualize the retinal layers and vessels which shows encouraging results in the study of various neurological conditions, including dementia. This review aims to succinctly sum up the present state of knowledge and provide critical insight into emerging patterns of OCTA biomarker values in Alzheimer’s disease and vascular dementia. According to the current literature, vessel density seems to be a common biomarker for both forms; inner retinal layer thickness might represent a biomarker preferentially affected in degenerative dementia including Alzheimer’s, while, in contrast, the outer-layer thickness as a whole justifies attention as a potential vascular dementia biomarker. Radial peripapillary capillary density should also be further studied as a biomarker specifically linked to vascular dementia.

Objective:The objective of this study was to investigate the pattern and severity of cognitive and language impairment in Greek patients with Relapsing-remitting (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS), relative to control participants.Method:A prospective study was conducted in 27 patients with multiple sclerosis (PwMS), (N= 15) with RRMS, (N= 12) with SPMS, and (N= 12) healthy controls. All participants were assessed with a flexible comprehensive neuropsychological – language battery of tests that have been standardized in Greece and validated in Greek MS patients. They were also assessed on measures of disability (Expanded Disability Status Scale; EDSS), fatigue (Fatigue Severity Scale; FSS) and depression (Beck Depression Inventory - fast screen; BDI-FS).Results:Our results revealed that groups were well matched on baseline demographic and clinical characteristics. The two clinical groups (RRMS; SPMS) did not differ on overall global cognitive impairment but differed in the initial encoding of verbal material, mental processing speed, response inhibition and set-shifting. RRMS patients differed from controls in the initial encoding of verbal material, learning curve, delayed recall of verbal information, processing speed, and response inhibition. SPMS patients differed in all utilized measures compared to controls. Moreover, we noted increased impairment frequency on individualized measures in the progressive SPMS group.Conclusion:We conclude that MS patients, irrespective of clinical subtype, have cognitive deficits compared to healthy participants, which become increasingly worse when they convert from RRMS to SPMS.On the contrary,the pattern of impairment remains relatively stable.

Recent studies by Bastiaanse and colleagues found that time reference is selectively impaired in people with nonfluent agrammatic aphasia, with reference to the past being more difficult to process than reference to the present or to the future. To account for this dissociation, they formulated the PAst DIscourse LInking Hypothesis (PADILIH), which posits that past reference is more demanding than present/future reference because it involves discourse linking. There is some evidence that this hypothesis can be applied to people with fluent aphasia as well. However, the existing evidence for the PADILIH is contradictory, and most of it has been provided by employing a test that predominantly taps retrieval processes, leaving largely unexplored the underlying ability to encode time reference-related prephonological features. Within a cross-linguistic approach, this study tests the PADILIH by means of a sentence completion task that 'equally' taps encoding and retrieval abilities. This study also investigates if the PADILIH’s scope can be extended to fluent aphasia. Greek- and Italian-speaking individuals with aphasia participated in the study. The Greek group consisted of both individuals with nonfluent agrammatic aphasia and individuals with fluent aphasia, who also presented signs of agrammatism. The Italian group consisted of individuals with agrammatic nonfluent aphasia only. The two Greek subgroups performed similarly. Neither language group of participants with aphasia exhibited a pattern of performance consistent with the predictions of the PADILIH. However, a double dissociation observed within the Greek group suggests a hypothesis that may reconcile the present results with the PADILIH.

Multiple sclerosis (MS) is a chronic, immune-mediated, inflammatory, and degenerative disease of the central nervous system (CNS) that affects both white and gray matter. Various mechanisms throughout its course, mainly regarding gray matter lesions and brain atrophy, result in cognitive network dysfunction and can cause clinically significant cognitive impairment in roughly half the persons living with MS. Altered cognition is responsible for many negative aspects of patients' lives, independently of physical disability, such as higher unemployment and divorce rates, reduced social activities, and an overall decrease in quality of life. Despite its devastating impact it is not included in clinical ratings and decision making in the way it should be. It is interesting that only half the persons with MS exhibit cognitive dysfunction, as this implies that the other half remain cognitively intact. It appears that a dynamic balance between brain destruction and brain reorganization is taking place. This balance acts in favor of keeping brain systems functioning effectively, but this is not so in all cases, and the effect does not last forever. When these systems collapse, functional brain reorganization is not effective anymore, and clinically apparent impairments are evident. It is therefore important to reveal which factors could make provision for the subpopulation of patients in whom cognitive impairment occurs. Even if we manage to detect this subpopulation earlier, effective pharmaceutical treatments will still be lacking. Nevertheless, recent evidence shows that cognitive rehabilitation and neuromodulation, using non-invasive techniques such as transcranial magnetic or direct current stimulation, could be effective in cognitively impaired patients with MS. In this Mini Review, we discuss the mechanisms underlying cognitive impairment in MS. We also focus on mechanisms of reorganization of cognitive networks, which occur throughout the disease course. Finally, we review theoretical and practical issues of neurorehabilitation and neuromodulation for cognition in MS as well as factors that influence them and prevent them from being widely applied in clinical settings.

Objective: We investigated: (i) the cognitive performance of type 2 diabetes mellitus (T2DM) patients compared to healthy control participants and (ii) the Health-related Quality of life (HRQOL) of type 2 diabetics with neuropsychological deficits.

Background A recent systematic review found that language deficits are not very common in individuals with multiple sclerosis (MS). However, there are significant gaps in our knowledge about language abilities in MS. For instance, morphosyntactic production has not been explored adequately thus far. This study investigated verb-related morphosyntactic production in MS focusing on Greek, a morphologically rich language. Methods A sentence completion task tapping into the production of subject-verb agreement, time reference/tense, and grammatical aspect was administered to 39 Greek-speaking individuals with MS [25 individuals with relapsing-remitting MS (RRMS group) and 14 individuals with secondary progressive MS (SPMS group)]. The task included only regular verbs. Generalized linear mixed-effects models were used to investigate the ability of individuals with MS to produce the above-mentioned morphosyntactic categories. Results Overall, the RRMS and SPMS groups performed significantly worse than their matched control groups. Moreover, all four groups performed significantly worse on grammatical aspect than on subject-verb agreement and time reference. The difference between subject-verb agreement and time reference was not significant in any of the four groups. The overall performances of the RRMS and SPMS groups did not differ significantly. Conclusion Individuals with MS are impaired in verb-related morphosyntactic production. Moreover, the pattern of performance of individuals with MS is identical to that exhibited by neurologically healthy individuals. Thus, the production performance of individuals with MS on verb inflection differs from that of healthy controls quantitatively but not qualitatively.

Objectives The purpose of this study was to generate normative data on the Symbol Digits Modalities Test (SDMT) for the written and oral versions in the Greek adult population. We also investigated the test’s validity in discriminating the performance of healthy adults from two groups of adults diagnosed with relapsing remitting (RRMS) and secondary progressive (SPMS) multiple sclerosis. Method The sample consisted of 609 healthy men and women between the ages of 18 and 65. All participants were monolingual native Greek adult speakers. Each healthy participant was administered either the written (n = 460) or oral (n = 149) versions of the SDMT. Discriminant validity was examined by comparing 35 healthy participants who had completed the oral version of the SDMT to 35 age - and education-matched RRMS and SPMS patients. Results Linear regression models explained between 36% and 55% of the variance in the SDMT oral and written version scores. Age was the strongest predictor of difference in SDMT written and oral version performance, followed by education that also accounted for a further proportion of the SDMT variance. On the contrary, gender was found not to contribute significantly to the variance in the SDMT for either the written or the oral versions. As a result, age- and education-adjusted norms were generated. Regarding the tests discriminative validity, we found that both MS patient groups scored significantly lower than the healthy group. Conclusions This is the first study to provide comprehensive normative data for the SDMT in the adult population in Greece, impacting the future practice of neuropsychological assessment in this country.

Background: Spontaneous spinal epidural hematomas (SSEHs) are often attributed to anticoagulation. Although they are rare, they may contribute to significant morbidity and mortality. Case Description: An 83-year-old female with a history of atrial fibrillation on apixaban, presented with 4 days of back pain, progressive lower extremity weakness and urinary retention. When the patient’s MRI showed a dorsal thoracolumbar SSEH, the patient underwent a T10–L3 laminectomy for hematoma evacuation. Within 2 postoperative months, her neurological deficits fully resolved. Conclusion: Apixaban is associated with SSEH resulting in severe neurological morbidity and even mortality. Prompt MRI imaging followed by emergency surgical decompressive surgery may result in full resolution of neurological deficits.

Cognitive impairment is frequently encountered in multiple sclerosis (MS) affecting between 40–65% of individuals, irrespective of disease duration and severity of physical disability. In the present multicenter randomized controlled trial, fifty-eight clinically stable RRMS patients with mild to moderate cognitive impairment and relatively low disability status were randomized to receive either computer-assisted (RehaCom) functional cognitive training with an emphasis on episodic memory, information processing speed/attention, and executive functions for 10 weeks (IG; n=32) or standard clinical care (CG; n=26). Outcome measures included a flexible comprehensive neuropsychological battery of tests sensitive to MS patient deficits and feedback regarding personal benefit gained from the intervention on four verbal questions. Only the IG group showed significant improvements in verbal and visuospatial episodic memory, processing speed/attention, and executive functioning from pre - to postassessment. Moreover, the improvement obtained on attention was retained over 6 months providing evidence on the long-term benefits of this intervention. Group by time interactions revealed significant improvements in composite cognitive domain scores in the IG relative to the demographically and clinically matched CG for verbal episodic memory, processing speed, verbal fluency, and attention. Treated patients rated the intervention positively and were more confident about their cognitive abilities following treatment.

Tentorium is a rare location of the brain dural arteriovenous fistulae (DAVF) consisting

We examined the utility of the Test of Everyday Attention for Children (TEA-Ch) for Greek children. Discrete and regression-based norms, controlling for demographic characteristics and intelligence, were derived from the performance of 172 children. We also assessed the ability of the TEA-Ch to differentiate children with ADHD-Combined Type (ADHD-C) from healthy matched peers. Children with ADHD-C displayed dysfunction in multiple attentional domains. Discriminant function analysis indicated that two subtests (Sky Search and Walk, Don't Walk) correctly classified 84.2% of children with ADHD-C.

Communication in humans activates almost every part of the brain. Of course, the use of language predominates, but other cognitive functions such as attention, memory, emotion, and executive processes are also involved. However, in order to explain how our brain “understands,” “speaks,” and “writes,” and in order to rehabilitate aphasic disorders, neuroscience has faced the challenge for years to reveal the responsible neural networks. Broca and Wernicke (and Lichtheim and many others), during the 19th century, when brain research was mainly observational and autopsy driven, offered fundamental knowledge about the brain and language, so the Wernicke-Geschwind model appeared and aphasiology during the 20th century was based on it. This model is still useful for a first approach into the classical categorization of aphasic syndromes, but it is outdated, because it does not adequately describe the neural networks relevant for language, and it offers a modular perspective, focusing mainly on cortical structures. During the last three decades, neuroscience conquered new imaging, recording, and manipulation techniques for brain research, and a new model of the functional neuroanatomy of language was developed, the dual stream model, consisting of two interacting networks (“streams”), one ventral, bilaterally organized, for language comprehension, and one dorsal, left hemisphere dominant, for production. This new model also has its limitations but helps us to understand, among others, why patients with different brain lesions can have similar language impairments. Furthermore, interesting aspects arise from studying language functions in aging brains (and also in young, developing brains) and in cognitively impaired patients and neuromodulation effects on reorganization of brain networks subserving language. In this selective review, we discuss methods for coupling new knowledge regarding the functional reorganization of the brain with sophisticated techniques capable of activating the available supportive networks in order to provide improved neurorehabilitation strategies for people suffering from neurogenic communication disorders.

In this review, we explore current literature and assess evidence linking secondary (acquired) alexithymia to aberrant humor processing, in terms of their neurobiological underpinnings. In addition, we suggest a possible common neuropathological substrate between secondary alexithymia and deficits in humor appreciation, by drawing on neurophysiologic and neuroradiological evidence, as well as on a recent and unique single-case study showing the cooccurrence of secondary alexithymia and deficit in humor appreciation. In summary, what emerges from the literature is that the cortical midline structures, in particular the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the insular cortex, seem to play a crucial role in the expression of both alexithymia and defective humor processing, while though to a lesser extent, a right hemisphere and bilateral frontoparietal contribution becomes evident. Neurobiological evidence of secondary alexithymia and aberrant humor processing points to the putative role of ACC/mPFC and the insular cortex in representing crucial processing nodes whose damage may produce both the above clinical conditions. We believe that the association of secondary alexithymia and aberrant humor processing, especially humor appreciation deficit, and their correlation with specific brain regions, mainly ACG/mPFC, as emerged from the literature, may be of some heuristic importance. Increased awareness on this topic may be of aid for neurosurgeons when accessing emotion-relevant structures, as well as for neuropsychologists to intensify their efforts to plan evidence-based neurorehabilitative interventions to alleviate the deleterious effects of such interpersonal communication deficits.

Cognitive impairment is present in up to 65% of Relapsing Remitting Multiple sclerosis (RRMS) patients and can be extremely debilitating. Although deficits in episodic memory and processing speed occur more frequently than executive deficits, executive dysfunction tends to have a significant impact on MS patients' ability to generate strategies, think divergently, solve and estimate problems, and reason in abstract terms with substantial negative impacts on activities of daily living. In the present study we investigated perfusion detection rate and pattern, as well as the association between perfusion rates and cognitive dysfunction in cognitively impaired RRMS patients.We present findings from 17 cognitively impaired RRMS patients who were evaluated with a comprehensive neuropsychological battery and additionally evaluated by brain perfusion radiopharmaceutical technetium-99m hexamethyl-propylene amine oxime (RRMS patients had hypoperfusion in several predefined Brodmann areas and lobes of the brain, relatively to demographically matched healthy controls according to an established normative database NeuroGam™. However, we noted blood flow reduction, mainly in the frontal lobes and other related prefrontal areas, involving both hemispheres, but with asymmetric left hemisphere predominance. Moreover, associations between measures of response inhibition, set shifting (executive functions) and severity of hypoperfusion in the left frontal lobes were also established.Cerebral hypoperfusion is an integral feature of MS pathology. Executive dysfunction is associated with robust cerebral perfusion deficits in the frontal and prefrontal cortex of cognitively impaired RRMS patients.

Cognitive impairment is common in multiple sclerosis (MS), but deficits tend to be more pronounced in progressive MS, negatively impacting daily functional capacity. Despite this, most cognitive rehabilitation (CR) interventions to date have focused on relapsing-remitting MS (RRMS). Moreover, information on the efficacy of CR in progressive MS is limited and controversial. The present study investigated the efficacy of a home based, computer assisted cognitive rehabilitation (HBCACR) intervention (RehaComThis was a randomized, multi site, sham controlled trial. Thirty six (36) individuals with SPMS, naïve to the RehaCom software, with cognitive deficits were randomized to the treatment (IG; n= 19) or control group condition (CG; n=17). Treatment with the RehaCom modules consisted of 24 domain and task specific, 45 minute session's over an 8-week period, three sessions per week, applied by each patient at home. The CG completed non specific computer based activities at home with the same frequency and duration. Primary cognitive outcome measures included the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, and secondary outcome measures for depression (BDI-FS), fatigue (MFIS), and quality of life (EuroQol EQ-5D) visual analogue scale (VAS).The two groups were well matched on demographic and clinical characteristics, cognitive reserve and severity of cognitive deficits at baseline assessment. At post treatment assessment the IG group showed significant improvements with large effect sizes; in verbal learning [z = -4.759, p.0005, g = 2.898], visuospatial memory [z = -3.940, p.0005, g = 1.699] and information processing speed [z= -4.792, p.0005, g = 2.980], compared with the sham control group. We also found significant between group differences on physical [z=-3.308, p = .001, g= -.604], cognitive [z = -4.011, p.0005, g = -1.654], psychosocial [z= 3.308, p = .010, g = -.940], and general fatigue impact [z= -2.623, p = .008, g = -.519], depression severity [z = -2.730, p = .006, g = -.519], and quality of life [z= -4.239, p.0005, g = -1.885] in favor of the treated group.These data provide the first evidence supporting the efficacy of computer based restorative cognitive rehabilitation applied at home exclusively in SPMS patients, suggesting that adaptive neuroplasticity may occur after functional cognitive training in progressive MS. Improved cognitive functioning in combination with mood augmentation appear to have ameliorated fatigue, which impacted daily functioning activity and culminated in improved health related quality of life.

Cognitive health in HIV-infected persons continues to be an important area of investigation, especially as the HIV epidemic is aging. Understanding the factors that may contribute to, or guard against, cognitive decline in the aging HIV population is necessary to develop and evaluate treatments that improve outcomes and reduce elderly dementia risk. In this issue of Neurology ®, a complex study1 focusing on men's cognitive health using data from the prospective Multicenter AIDS Cohort Study (MACS) shows established but also unexpected relationships among midlife adiposity, and waist circumference, HIV status, and 10-year trajectory of cognitive performance.

Introduction Cognitive impairment is an important predictor of quality of life at all stages of MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. Objective The aim of the study was to designate the MRI marker that predicts cognitive decline and explore its effect on every day activities and employment status. Methods 50 RRMS patients and 31 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Everyday activities were evaluated with the instrumental activities of daily living (IADL) scale and employment status. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, corpus callosum and thalamic atrophy. Results The frequency of cognitive dysfunction for our RRMS patients was 38%. RRMS patients differed significantly from controls on the TMTA, TMTB, phonological verbal fluency task, memory, psychomotor speed, reaction time and cognitive flexibility. Neuropsychological measures had a strong correlation with all MRI atrophy measures and a weak or moderate correlation with lesion volume. Psychomotor speed was the most sensitive marker for IADL, while memory and TMTB for employment status. Thalamic area was the most sensitive MRI marker for memory, psychomotor speed and TMTB.. Conclusion Thalamic atrophy predicts the clinically meaningful cognitive decline in our RRMS patients.

Importance Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by relapses and a progressive course that may lead to accumulation of physical and cognitive disability. Cognitive training interventions seem to improve the cognitive performance of MS patients. The aim of the present meta-analysis is to quantitatively investigate the effect of computer-based cognitive rehabilitation on the neuropsychological performance of patients with MS. Methods We performed a systematic review of the PubMed database to identify available studies that performed computer-based cognitive training in MS patients. Studies should have reported pre- and post-cognitive training neuropsychological tests scores and included both intervention and placebo/no-intervention MS groups. We analyzed the effect of computer-based cognitive rehabilitation on individual neuropsychological tests, on specific functional domains, and on overall cognition performance. The effect-size of cognitive training pre- and post-treatment compared to placebo/ no-intervention was estimated using the standardized mean difference (SMD). The 95% confidence intervals (CI) were estimated using a Z test by comparing the final values. Baseline between-group differences in selected outcomes were estimated with ANOVA. Results In total, 9 studies fulfilled the criteria for inclusion and were inserted in the quantitative analysis. Computer-based cognitive training was found to improve the performance in the memory domain of MS patients compared to control interventions (SMD, 0.22; 95% CI 0.01–0.43; p = 0.04). Moreover, in the subgroup analysis, cognitive training demonstrated significant effects in Selective Reminding Test (SRT) delay memory (SMD, 0.58; 95% CI 0.29–0.87; p Conclusions The present meta-analysis revealed a significant effect for computer-based cognitive training on the performance of the memory domain of patients with MS. This finding may have significant implications in the current treatment practice when cognitive decline is detected in MS patients.

Depression and other nonmotor manifestations such as sleep disturbances are common and disabling features of Parkinson disease (PD).1 These symptoms contribute to poor quality of life and impaired cognitive performance and lead to increased morbidity and mortality in the PD population. Current nonpharmacologic treatment options for depression and other nonmotor symptoms of PD are limited. Pharmacotherapy may be associated with undesirable adverse effects. There is therefore a great need to develop novel treatment modalities.

Background: Families of individuals with psychotic disorders are playing a major role in the care of their relatives, but report poorer physical competence, elevated symptoms of psychological distress and more psychopathological characteristics. Aim: To compare psychopathological characteristics demonstrated by caregivers of psychotic patients in Greece who participated in support groups organized by non-governmental mental health organizations (NGOMH) compared to caregivers who did not. Methods: Participants were caregivers of a psychotic patient assigned to either the intervention group ( n = 165) or the non-intervention group ( n = 345) according to specific criteria. Participants were assessed for psychopathological characteristics through clinical interviews and with the Symptom Checklist 90–Revised (SCL-90-R). Results: Participants who did not take part in the support groups had higher levels of psychopathological characteristics on the dimensions of interpersonal sensitivity ( t = −2.065, p = .003), depression ( t = 1.043, p = .007), anxiety ( t = 1.001, p = .010), hostility ( t = −4.345, p Conclusion: Participation in support groups and sharing of emotional expression, thoughts and ideas help the caregivers deal with their physical and psychological demands related to the caregiver load. As such, intervention strategies offered to caregivers in the support groups appear to positively contribute to the family with a psychotic patient and improve the quality of life of both patients and their main caregivers.

Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients.

Orthostatic hypotension (OH) is associated with cognitive impairment in otherwise healthy individuals as well as among those with neurodegenerative diseases. There is much current interest in the OH–cognitive impairment connection.1–4 OH and cognitive impairment are both common in Parkinson disease and can lower quality of life. Nonpharmacologic and pharmacologic treatments for OH are readily available, while treatments to modify the course of neurodegenerative cognitive impairment are nil. If the association between OH and cognitive impairment is causal and OH damages the brain, a promising window of therapeutic opportunity suggests itself. Alternately, OH and cognitive impairment are simply markers of a shared pathologic substrate.

Episodic memory impairment is a robust correlate of familial risk for schizophrenia (SZ) and bipolar disorder (BD); still much is unknown about the processes that underlie this deficit and how they may be implicated in BD and SZ. We examined the possibility that (a) episodic memory impairment may arise from abnormalities in the cognitive control of interference between task-relevant and task-irrelevant memories during retrieval; inability to suppress task-irrelevant representations could give rise to intrusions of inappropriate memories and increased rate of forgetting, (b) cognitive control deficits during retrieval may be differentially affected by familial predisposition to SZ or BD. We examined episodic memory in relatives of patients with SZ (SZ-R) (n = 15) or BD (BD-R) (n = 17) compared to healthy controls (n = 23) using the California Verbal Learning Test (CVLT) and the Doors and People Test (DPT). All relatives were free of any psychiatric morbidity and were matched to controls on age, sex, educational achievement and general intellectual ability. During the CVLT, both relatives' groups made significantly more perseverative recall errors than controls. However, intrusion errors were significantly increased in SZ-R only. SZ-R also showed increased rate of forgetting in the DPT while BD-R were comparable to controls. Familial predisposition to SZ, compared to that of BD, was associated with significantly greater impairment in cognitive control processes during episodic memory retrieval with some evidence of specificity for SZ in connection with mechanisms relating to increased forgetting.

Patients with schizophrenia demonstrate impaired action verbal fluency, but no study has examined verb-noun differences using picture naming. The present study compared object and action naming in 20 adult patients diagnosed with schizophrenia (DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Text Revision; American Psychiatric Association, 2000) criteria, and 20 demographically matched healthy controls, using pictures. Overall, schizophrenic patients showed poorer naming than controls on all measures of object and action lexical semantic access and retrieval despite normal comprehension for action and object names. Results further indicated that action names were significantly more difficult to retrieve than object names in schizophrenic patients. The absence of dissociation in comprehension of action and object names but semantic errors in naming both classes suggests intact conceptual-semantic stores among middle-aged community-dwelling outpatients with schizophrenia but difficulties mapping semantics onto the lexicon. Action-naming impairments can arise from both semantic and postsemantic origins in schizophrenia. These results have implications for the neurobiology of language given the association between both schizophrenia and verb processing and frontal damage. Moreover, the issue being addressed is important for a cognitive characterization of schizophrenia and for an understanding of the representations of action and object names in the brain. Refereed/Peer-reviewed

The present study investigated differences and associations between cortical perfusion, nigrostriatal dopamine pathway and neuropsychological functions in different stages of Parkinson’s disease (PD). We recruited 53 non-demented PD patients divided into four groups according to the Hoehn and Yahr (HY) staging system and 20 healthy controls who were used in the comparison of the neuropsychological findings. Each patient underwent two separate brain single photon emission computed tomography (SPECT) studies (perfusion and dopamine transporter binding) as well as neuropsychological evaluation. Perfusion images of each patient were quantified and compared with a normative database provided by the NeuroGam software manufacturers. Mean values obtained from the cortical areas and neuropsychological measures in the different groups were also compared by analysis of covariance (ANCOVA) controlling for disease duration and educational level. We found cognitive deficits especially in the late PD stages (HY 3, 4 and 5) compared to the early stages (HY 1 and 2) and associations between cognitive decrements and cortical perfusion deterioration mainly in the frontal and posterior cortical areas. Compared with controls, PD patients showed impairments of cognition and cerebral perfusion that increased with clinical severity. Furthermore, we found a significant correlation between the performance on the phonemic fluency task and regional cerebral blood flow (rCBF) in the left frontal lobe. Dopamine transporter binding in the left caudate nucleus significantly correlated with blood flow in the left dorsolateral prefrontal cortex (DLPFC), but not with measures of executive functions. There are significant cognitive and perfusion deficits associated with PD progression, implying a multifactorial neurodegeneration process apart from dopamine depletion in the substantia nigra pars compacta (SNc).

Multiple sclerosis is the most common non-traumatic neurodegenerative disease in adults. Most of the patients present with both physical and mental deficits which reflect the dissemination of the lesions in the central nervous system, produced by the inflammatory process. The incomplete recovery after relapses, the accumulation of new deficits and the progressive nature of the condition interfere with daily activities of individuals and have a negative impact on their well-being. Indeed, studies show that quality of life measurements are constantly lower in patients with multiple sclerosis. Estimation of health-related quality of life is being increasingly recognized as necessary when analysing the effectiveness of treatment modalities and for the follow up of patients with chronic diseases such as multiple sclerosis. Current immunomodulatory interventions that are shown to reduce the frequency of relapses and delay disease progression might also have a positive effect on quality of life measurements. Additive pharmacological agents that target cognitive impairments and common symptoms such as depression, fatigue and pain, along with life-style modifications and rehabilitation programmes are also important for the appropriate management that aims to improve quality of life.

Research has recently focused on cognitive dysfunction in multiple sclerosis (MS). Cognitive deficits are frequently encountered in patients and account for important impairment in quality of life, therefore posing a major therapeutic challenge for the disease. We presently review studies on cognitive effects of pharmacological treatments in MS. There is evidence for a possible beneficial effect of immunomodulatory treatments, particularly of interferons, and also of acetylcholinesterase inhibitors on cognition in MS, which, however, requires evaluation in larger, multi-centre, longitudinal studies. Methodological issues and future prospects regarding the investigation of this issue are also discussed.