Cognitive trajectories preluding the onset of different dementia entities: a descriptive longitudinal study using the NACC database.

OBJECTIVE: To describe the 10-year preclinical cognitive trajectories of older, non-demented individuals towards the onset of the four most prevalent types of dementia, i.e., Alzheimer's disease(AD), Lewy body(LBD), vascular(VD) and frontotemporal dementia(FTD). METHODS: Our analysis focused on data from older (≥ 60years) NACC (National Alzheimer's Coordinating Center) participants. Four distinct presymptomatic dementia groups (AD-LBD-VD-FTD) and a comparison group of cognitively unimpaired(CU) participants were formed. Comprehensive cognitive assessments involving verbal episodic memory, semantic verbal fluency, confrontation naming, mental processing speed - attention and executive function - cognitive flexibility were conducted at baseline and on an approximately yearly basis. Descriptive analyses (adjusted general linear models) were performed to determine and compare the yearly cognitive scores of each group throughout the follow-up. Exploratory analyses were conducted to estimate the rates of cognitive decline. RESULTS: There were 3343 participants who developed AD, 247 LBD, 108 FTD, 155 VD and 3398 composed the CU group. Participants with AD performed worse on episodic memory than those with VD and LBD for about 3 to 4 years prior to dementia onset (the FTD group documented an intermediate course). Presymptomatic verbal fluency and confrontation naming trajectories differentiated quite well between the FTD group and the remaining dementia entities. Participants with incident LBD and VD performed worse than those with AD on executive functions and mental processing speed-attention since about 5 years prior to the onset of dementia, and worse than those with FTD more proximally to the diagnosis of the disorder. CONCLUSIONS: Heterogeneous cognitive trajectories characterize the presymptomatic courses of the most prevalent dementia entities.

Cognitive Rehabilitation for Patients with Schizophrenia: A Narrative Review of Moderating Factors, Strategies, and Outcomes.

OBJECTIVE: Antipsychotic drugs constitute the basis of schizophrenia therapy; however, available pharmaceutical agents lack efficacy for treating the cognitive deficits caused by the illness. The aim of the present work is to present current data regarding cognitive rehabilitation of schizophrenia, providing information and guidance to health professionals. METHOD: A literature search was conducted in the PubMed and Google Scholar Databases from inception up to 1/9/2022. Relevant articles were explored for factors affecting cognitive function, including genetics, psychopathology, time in the course of the illness, and drug therapy. Characteristics and outcome of cognitive rehabilitation programs are briefly presented. RESULTS: A total of 562 relevant articles were retrieved, 39 of which were selected for the review. Factors contributing to a favorable outcome are young age, early phase of disease, symptomatic control of hostility and conceptual disorganization, lack of negative symptoms, management of drug side effects, and cognitive and cortical reserve. Some evidence for a procognitive effect seems to exist for atypical antipsychotics, clozapine, aripiprazole, memantine, modafinil, d-serine, and cycloserine. The Val/Val polymorphism of the COMT gene seems to be associated with worse outcome. Specific remediation strategies include programs such as Cognitive Enhancement Therapy (CET), Cognitive Adaptation Training (CAT), and RehaCom Cognitive Therapy Software, among others, all employing a range of techniques, from paper-and-pencil to computer-assisted, bottom-up, or top-down approaches, and varying neurocognitive targets. CONCLUSION: Cognitive symptoms, closely related to functional impairment, still remain a therapeutic challenge. Cognitive rehabilitation strategies are as yet the only treatment modality offering cognitive improvement to patients who struggle to recover.

Illiteracy, Neuropsychological Assessment, and Cognitive Rehabilitation: A Narrative Review.

OBJECT: Νeuropsychological assessment is particularly important for the accurate discrimination of cognitive abilities and weaknesses of patients in order to determine the appropriate therapeutic intervention. However, the reliability and validity of neuropsychological assessment appears to be influenced by a wide range of factors, including literacy and educational level. AIM: This systematic review evaluates neuropsychological tests appropriate for the valid assessment of illiterate individuals and the effectiveness of cognitive rehabilitation programs for illiterate and/or low-educated individuals according to the results of English language studies that have been published in the PubMed/Medline electronic database until August 2022 (no initiation date). RESULTS: 49 studies were included for neuropsychological assessment and 4 studies for cognitive rehabilitation. In terms of investigating the validity and reliability of neuropsychological tests for the assessment of healthy illiterate individuals, most studies concluded that for the majority of neuropsychological tests there is a significant difference in performance between healthy illiterate and literate individuals. However, there was consensus among studies that the performance of illiterate subjects was equivalent to the performance of literate subjects on tasks depicting colored and real objects. Regarding cognitive rehabilitation programs, all four studies concluded that they are effective in improving the cognitive functions of illiterate and/or low-literate patients with mild cognitive impairment and/or mild dementia. CONCLUSIONS: For the assessment of illiterate individuals, it is imperative that neuropsychological tests with high ecological validity (i.e., tests related to activities of daily living) be administered so as not to underestimate their cognitive functioning. At the same time, cognitive enhancement/stimulation programs seem to be effective in this population group; however, this area needs further investigation.

Noninvasive Brain Stimulation in Primary Progressive Aphasia: A Literature Review.

Primary progressive aphasia (PPA) is a gradually progressive clinical syndrome in which the first and predominant symptoms involve language and/or speech production that interfere with daily activities. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) appear to have a beneficial impact on many neurodegenerative pathologies. The current review investigated the impact of rTMS and tDCS on PPA patients. English language articles that have been published in the databases PubMed, and Scopus from 2007 to 2022 were included. Fifteen single-case or small-group studies were analyzed and presented. The majority of the literature findings point toward that the application of rTMS or tDCS may have a positive effect in improving symptoms such as verb production, action naming, phonemic-verbal fluency, grammatical comprehension, written spelling, and semantic features. In conclusion, our review provides additional evidence supporting that both types of stimulation may improve linguistic deficits, especially if they combined, speech therapy.

Repetitive Transcranial Magnetic Stimulation in Post-stroke Aphasia: Comparative Evaluation of Inhibitory and Excitatory Therapeutic Protocols: Narrative Review.

OBJECTIVE: Aphasia is a serious consequence of stroke resulting in difficulties in using language for communication with negative effects on patients' quality of life. The use of non-invasive repetitive transcranial magnetic stimulation (rTMS) is a novel approach in aphasia therapy, based on the knowledge gained by functional imaging technics of the brain. AIM: This review evaluates the effectiveness of rTMS on aphasia therapy according to the results of English language studies that have been published in the databases PubMed/Medline, Scopus, and Web of Science from 2011 to 2021. RESULTS: Twenty-seven studies were included in the review with 672 participants. The studies mainly concern the application of inhibitory rTMS on the right inferior frontal gyrus (rIFG) in the subacute and chronic phase, as well as excitatory rTMS of the unaffected language areas of the left cerebral hemisphere in the chronic phase after stroke. Most of the studies concluded that there was statistically significant improvement in various parameters of language including confrontation naming, repetition, and aphasia quotient. Three studies published results that doubt the effectiveness of rTMS. CONCLUSION: rTMS is a safe therapeutic method for aphasia treatment in the subacute and chronic phases after stroke. Its effectiveness is immediate as well as distant with a gradually decreasing therapeutic effect. Moreover, rTMS may supplement speech and language therapy as a priming factor. The most recognized method at this point in time is the application of suppressive rTMS on the right inferior frontal gyrus in combination with speech and language therapy.

Cognitive Neurorehabilitation in Epilepsy Patients via Virtual Reality Environments: Systematic Review.

OBJECTIVE: Epilepsy patients could possibly benefit from the remuneration observed in the use of virtual reality (VR) and virtual environments (VEs), especially in cognitive difficulties associated with visuospatial navigation (memory, attention, and processing speed). AIM: Research questions under consideration in the present systematic review are associated to VEs' efficiency as a cognitive rehabilitation practice in epilepsy and the particular VR methods indicated for epilepsy patients. To meet criteria, studies included participants suffering from any form of epilepsy and a methodological design with a structured rehabilitation program/model. Data were collected online, using academic databases. RESULTS: Fourteen studies were included in the literature review and 6 in the statistical analysis. ROBINS-I protocol was implemented to assess the risk of bias. An inverse variance analysis (random effects) of pooled estimates of differences was implemented, in the form of continuous data. Despite the heterogeneity of the studies, all of them agree on the beneficial aspects of VR and VEs in cognitive rehabilitation in relation to visuospatial memory, attention, and information processing speed. CONCLUSION: We suggest that patients suffering from epilepsy may benefit from the use of VR cognitive rehabilitation interventions, concerning visuospatial memory, attention, and information processing speed. However, further investigation is needed in order to gain a better understanding of the mechanisms involved in cognitive rehabilitation via VEs and establish efficient and dynamic rehabilitation protocols.

Lack of Association between CD33 rs3865444 and Amyotrophic Lateral Sclerosis: A Case-Control Study.

BACKGROUND: Microglial activation is considered to assume a role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). To date, the relationship between ALS and the rs3865444 polymorphism of the cluster of differentiation 33 (CD33) has not been explored. The current report aimed to investigate the potential connection between CD33 rs3865444 and ALS. METHODS: Patients diagnosed with sporadic ALS according to the revised El Escorial criteria, as well as age and sex matched community controls, were enrolled. Two evenly numbered, age and sex matched groups of 155 participants each were genotyped. RESULTS: No association was found between rs3865444 and ALS [log-additive odds ratio (OR) = 0.83 (0.57, 1.22), over-dominant OR = 0.86 (0.55, 1.36), recessive OR = 0.73 (0.25, 2.17), dominant OR = 0.82 (0.52, 1.29), co-dominant OR1 = 0.68 (0.23, 2.05) and co-dominant OR2 = 0.84 (0.53, 1.33)]. Moreover, no relationship was established between rs3865444 and the age of ALS onset based on both unadjusted and sex adjusted Cox-proportional hazards models. Finally, no association between rs3865444 and ALS was found in subgroup analyses based on the site of ALS onset (bulbar or spinal) and sex. CONCLUSIONS: The current analysis is the first to report that rs3865444 is not linked to ALS. Larger multi-racial studies are required to confirm these findings.

Analysis of SOD2 rs4880 Genetic Variant in Patients with Alzheimer's Disease.

A few gene loci that contribute to Alzheimer's Disease (AD) onset have been identified. Few studies have been published about the relationship between SOD2 rs4880 single nucleotide variant and AD, revealing inconsistent results. Therefore, the aim of the current study is to further examine the role of the SOD2 rs4880 in AD. We performed a case-control study with a total of 641 subjects (320 patients with probable AD, and 321 healthy controls). The statistical analysis was performed assuming five genetic models. The threshold for statistical significance was set at 0.05. The results revealed no association between SOD2 rs4880 and AD in any of the assumed genetic models that were examined [log-additive OR = 0.95 (0.76-1.19), over-dominant OR = 1.15 (0.85-1.57), recessive OR = 0.85 (0.59-1.22), dominant OR = 1.03 (0.72-1.47), and co-dominant OR1 = 1.10 (0.75-1.60) and OR2 = 0.90 (0.58-1.40)]. Adjustment for sex and subgroup analyses based on sex did not reveal any statistically significant results either. Based on our findings, SOD2 rs4880 does not appear to play a determining role in the risk of developing AD. Larger studies are warranted to elucidate the connection between rs4880 and AD.

Chronic hematoma superimposed to a large frontotemporal arachnoid cyst: evidence against crowding of audioverbal memory.

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 severity-threshold may exist below which inter-hemispheric reorganization of audioverbal memory is unlikely.

Vitamin D and tension-type headache: causal association or epiphenomenon?

Background-Purpose: Low serum vitamin D (VD) has been already associated with a series of highly prevalent pain-related conditions, including fibromyalgia, migraine and chronic widespread pain. Considering the potential interplay between VD and pain signalling pathways, the association of VD with tension-type headache (TTH) was reviewed.Methods: A multifaceted narrative approach assessing the relationship of serum VD with TTH and TTH parameters, as well as the efficacy of VD supplementation for the prevention of TTH, was fostered. MEDLINE, CENTRAL and EMBASE were comprehensively searched for this purpose, while Google Scholar was also explored according to a structured approach. ClinicalTrials.gov and European Union Clinical Trials Register were explored for ongoing prevention trials.Results: Although available evidence was suggestive of an association between VD and TTH, mainly of the chronic type, the causal nature of the association remains to be determined. Considering the lack of longitudinal evidence, this relationship could arguably reflect behavioural patterns of headache sufferers. On the other hand, evidence principally originated from tertiary clinical settings (severe comorbidity burden) and researchers tend to report a concomitant association of both entities with generalized musculoskeletal compromise. In this context, the association between TTH and VD may represent nothing more than a secondary by-product of the simultaneous relationship of other comorbid diseases-conditions with both TTH and low serum VD. Regarding its efficacious properties, only one ongoing trial specifically designed to explore the efficacy of VD in chronic TTH in adults was retrieved.Conclusions: There is no evidenced based indication for VD supplementation in TTH.

Aging and the Perception of Affective and Linguistic Prosody.

Investigations of affective prosodic processing have demonstrated a decline with aging. It is unclear, however, whether this decline affects all or specific emotions. Also, little is known about the ability of syntactic resolution ambiguity with the use of prosody in aging. Twenty older (age range = 70-75) and 20 younger adults (age range = 20-25) performed an affective (happiness, neutrality, sadness, surprise, fear, and anger) and a linguistic (subject/object ambiguities) prosody task. Relative to young participants, older participants faced difficulty decoding affective prosody, particularly negative emotions, and syntactic prosody, in particular the subject reading condition. A marginally positive correlation was found between the affective and syntactic prosody tasks in the group of older individuals, but no gender differences in either prosodic task. The findings of the affective prosody task are discussed under the prism of the Socioemotional Selectivity Theory, whereas general parsing strategies can account for the preference for the object reading condition.

Lack of association between TREM2 rs75932628 variant and amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease. Inflammatory processes are among the mechanisms that are implicated in ALS pathogenesis. The TREM2 rs75932628 T variant may influence the regulatory effect of TREM2 on inflammation. Studies regarding the role of the rs75932628 variant in ALS have yielded inconsistent results, so far. To assess the role of TREM2 rs75932628 on ALS risk. We genotyped 155 patients with sporadic ALS and 155 healthy controls for TREM2 rs75932628. We also merged and meta-analyzed our data with data from previous studies (with a total of 7524 ALS cases and 14,675 controls), regarding TREM2 rs75932628 and ALS. No ALS or healthy subjects carried the TREM2 rs75932628-T variant. Results from meta-analyses (overall approach and sensitivity analyses) yielded no significant results for possible connection between TREM2 rs75932628-T variant and ALS. Based on our results, TREM2 rs75932628 does not seem to play a determining role to the pathophysiology of ALS.

Pure word deafness due to bilateral temporal lobe ischemic stroke occurring at different time points over the years: a case report on the insight of brain language network reorganization.

Here we present a case of a native Greek male patient who presented clinically with sudden onset pure word deafness after an ischemic stroke in the temporoparietal region of the right hemisphere, but who had suffered an ischemic stroke 9 years previously in an adjacent area of the left hemisphere, causing aphasic symptoms which resolved quickly and almost completely. What makes this case interesting and novel is that it is the first case describing a patient whose ventral language comprehension circuit did not reorganize successfully due to damage of the adjacent right hemisphere language areas at a subsequent time.

CYP1A2 rs762551 polymorphism and risk for amyotrophic lateral sclerosis.

BACKGROUND: Genetic variability is considered to confer susceptibility to amyotrophic lateral sclerosis (ALS). Oxidative stress is a significant contributor to ALS-related neurodegeneration, and it is regulated by cytochromes P450 (CYPs), such as CYP1A2; these are responsible for the oxidative metabolism of both exogenous and endogenous substrates in the brain, subsequently impacting ALS. The function of CYP1A2 is largely affected by genetic variability; however, the impact of CYP1A2 polymorphisms in ALS remains underinvestigated. OBJECTIVE: This study aims to examine the possible association of ALS with the CYP1A2 rs762551 polymorphism, which codes for the high inducibility form of the enzyme. METHODS: One hundred and fifty-five patients with sporadic ALS and 155 healthy controls were genotyped for the CYP1A2 rs762551. Statistical testing for the association of CYP1A2 rs762551 with risk for ALS was performed using SNPstats. RESULTS: The CYP1A2 rs762551 C allele was associated with a decreased risk of ALS development. In the subgroup analysis according to the ALS site of onset, an association between CYP1A2 rs762551 and limb and bulbar onset of ALS was shown. Cox proportional-hazard regression analyses revealed a significant effect of the CYP1A2 rs762551 on the age of onset of ALS. CONCLUSIONS: Based on our results, a primarily potential link between the CYP1A2 rs762551 polymorphism and ALS risk could exist.

The Impact of Primary Progressive Aphasia on Picture Naming and General Language Ability.

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.

MOBP rs616147 Polymorphism and Risk of Amyotrophic Lateral Sclerosis in a Greek Population: A Case-Control Study.

Background and Objectives: To date, only one study has investigated the association between the rs616147 polymorphism of the Myelin-associated Oligodendrocyte Basic Protein (MOBP) locus and Amyotrophic Lateral Sclerosis (ALS). Materials and Methods: A case-control study was performed. Patients with definite sporadic ALS were prospectively and consecutively recruited from the inpatient and outpatient clinics of the Neurology Department of the General University Hospital of Larissa, Central Greece. Community based, age and sex matched healthy individuals with a free personal and family history constituted the control group. Results: A total of 155 patients with definite sporadic ALS and an equal number of healthy controls were genotyped. The power of our sample size was slightly above 80% and MOBP rs616147 was determined to be in Hardy-Weinberg Equilibrium among healthy participants (p = 1.00). According to the univariate analysis, there was no significant relationship between rs616147 and ALS [log-additive OR = 0.85 (0.61, 1.19), over-dominant OR = 0.73 (0.46, 1.15), recessive OR = 1.02 (0.50, 2.09), dominant OR = 0.74 (0.47, 1.16), co-dominant OR1 = 0.71 (0.44, 1.14) and co-dominant OR2 = 0.88 (0.42, 1.84). Additionally, the effect of rs616147 on the age of ALS onset was determined insignificant using both unadjusted and adjusted (sex, site of onset) cox-proportional models. Finally, rs616147 was not related to the site of ALS onset. Conclusions: Our study is the first to report the absence of an association between MOBP rs616147 and ALS among individuals of Greek ancestry. Additional, larger nationwide and multi-ethnic studies are warranted to shed light on the connection between rs616147 and ALS.

Quality of Life in Type 2 Diabetes Mellitus Patients with Neuropsychological Deficits.

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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Computerized cognitive rehabilitation for treatment of cognitive impairment in multiple sclerosis: an explorative study.

In this explorative study, forty-seven patients with relapsing-remitting multiple sclerosis were randomized to a custom 6-week cognitive rehabilitation intervention (n = 23) using the BrainHQTM web-based platform and to a control group condition (n = 24). Cognitive rehabilitation intervention consisted of two 40-minute sessions per week. All patients were tested with the Brief International Cognitive Assessment for Multiple Sclerosis battery, the Stroop Color-Word Test, and the trail making test, while the Beck Depression Inventory - Fast Screen questionnaire was used as a measure of mood and the cognitive reserve index as a measure of cognitive reserve. We used the reliable change index, to calculate clinically meaningful changes of performance, and to discriminate between responders and non-responders of this intervention. Statistically significant improvement of the group receiving treatment was observed mainly on measures of verbal and non-verbal episodic memory and, to a lesser extent, on reading speed, selective attention/response inhibition, and visual attention. Verbal memory and visual attention improvements remained significant after considering the corrected for multiple comparisons level of significance. According to reliable change index scores, 12/23 (52.2%) of patients in the intervention group presented meaningful improvement in at least one measure (Greek Verbal Learning Test: 26%, Brief Visuospatial Memory Test-Revised: 17.4%, Stroop-Words test: 13%). This explorative study provides evidence that, at least in the short term, cognitive rehabilitation may improve the cognitive performance of multiple sclerosis patients.

Cognitive functions and social cognition in multiple sclerosis: An overview.

Cognitive decline has been widely reported in patients with multiple sclerosis (MS) despite its clinical heterogeneity, at all stages and in all subtypes of the disease. Deficits are most commonly present in attention, processing speed, working memory, verbal fluency and executive function. However, MS patients also show decreased performance in tasks related to social cognition, i.e. mental operations thatdrive interpersonal skills such as social perception, empathy and theory of mind. Social cognitive deficits are an underestimated but important aspect of impairment in MS, reflecting how people process, store, and apply information in social interactions. Deficits in these domains have been associated with reduced social and psychological quality of life, even after controlling for severity and duration of the disease, age, and neurocognitive performance. Social cognition impairment is not entirely dependent on and parallel to general cognitive dysfunction, given that some patients experience disorganization of their social life before a significant or detectable cognitive impairment. The decrease in performance of social cognition tasks may reflect changes in brain activity and brain structure, either general or regional. Both subtle diffuse pathology and acute local lesions have at least partially independent effects on aspects of social cognition. The observed white matter damage contributes to a mechanism of disruption in the network of brain connections involved in social cognition. Undoubtedly, there is a wide variability in the relationship of social cognitionand neuroanatomical findings, not only due to the brain's complex connectivity, but also to the lack of a unique operative definition of these cognitive domains. Furthermore, it is difficult to compare study results, given the variability of clinical presentations in all stages of the disease.More research would contribute in understanding social cognition deficits better and in determining whether and what kind of training could be beneficial.

Robust regional cerebral blood flow perfusion deficits in relapsing-remitting multiple sclerosis patients with executive function impairment.

OBJECTIVES: 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. METHODS: 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 (99mTc HMPAO). RESULTS: 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. CONCLUSION: 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.