Publications by authors named "Ioannis Zalonis"

39 Publications

Neuropsychological Assessment Should Always be Considered in Myotonic Dystrophy Type 2.

Cogn Behav Neurol 2021 Mar 3;34(1):1-10. Epub 2021 Mar 3.

First Department of Neurology, Medical School, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Myotonic dystrophies (DMs) are hereditary, multisystem, slowly progressive myopathies. One of the systems they affect is the CNS. In contrast to the well-established cognitive profile of myotonic dystrophy type 1 (DM1), only a few studies have investigated cognitive dysfunction in individuals with myotonic dystrophy type 2 (DM2), and their findings have been inconsistent. To identify the most commonly affected cognitive domains in individuals with DM2, we performed a formal comprehensive review of published DM2 studies. Using the terms "myotonic dystrophy type 2" AND "cognitive deficits," "cognitive," "cognition," "neuropsychological," "neurocognitive," and "neurobehavioral" in all fields, we conducted an advanced search on PubMed. We read and evaluated all of the available original research articles (13) and one case study, 14 in total, and included them in our review. Most of the research studies of DM2 reported primary cognitive deficits in executive functions (dysexecutive syndrome), memory (short-term nonverbal, verbal episodic memory), visuospatial/constructive-motor functions, and attention and processing speed; language was rarely reported to be affected. Based on the few neuroimaging and/or multimodal DM2 studies we could find, the cognitive profile of DM2 is associated with brain abnormalities in several secondary and high-order cortical and subcortical regions and associative white matter tracts. The limited sample size of individuals with DM2 was the most prominent limitation of these studies. The multifaceted profile of cognitive deficits found in individuals with DM2 highlights the need for routine neuropsychological assessment at both baseline and follow-up, which could unveil these individuals' cognitive strengths and deficits.
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http://dx.doi.org/10.1097/WNN.0000000000000263DOI Listing
March 2021

Face-Name Associative Memory Performance Among Cognitively Healthy Individuals, Individuals With Subjective Memory Complaints, and Patients With a Diagnosis of aMCI.

Front Psychol 2020 9;11:2173. Epub 2020 Sep 9.

First Department of Neurology, Faculty of Medicine, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.

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http://dx.doi.org/10.3389/fpsyg.2020.02173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517892PMC
September 2020

The severity of executive dysfunction among different PD-MCI subtypes.

Appl Neuropsychol Adult 2020 Jul 7:1-5. Epub 2020 Jul 7.

First Department of Neurology, National and Kapodistrian University of Athens, Aeginition Hospital, Athens, Greece.

Aim to examine the severity of executive dysfunction among different Parkinson's disease (PD)-mild cognitive impairment (MCI) subtypes in the early stages of the disease. The final sample consisted of 65 patients with mild PD progression. Based on neuropsychological measures, our sample was categorized into three PD-MCI subtypes: (1) PD-MCI executive group ( = 24), (2) PD-MCI executive plus memory group ( = 22), and (3) PD-MCI executive plus visuospatial group ( = 19). Patients' executive functions were evaluated with the Trail Making Test-Part B (TMT-B) and Stroop Neuropsychological Screening Test (SNST) for mental flexibility and inhibitory control, respectively. One-way ANOVA results indicated significant differences among the three subgroups on TMT-B and SNST performance. Tukey honestly significant different (HSD) tests revealed that the PD-MCI executive plus visuospatial group had lower performances on both executive measures than the other two groups. Contrastingly, no significant differences were observed between the PD-MCI executive group and PD-MCI executive plus memory group. Our results indicated that the severity of executive dysfunction varies across different PD-MCI subtypes. These findings are discussed within the framework of the dual syndrome hypothesis and highlight the utility of determination of executive impairment severity for effective clinical management of patients with PD.
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http://dx.doi.org/10.1080/23279095.2020.1786832DOI Listing
July 2020

A longitudinal study of cognitive function in multiple sclerosis: is decline inevitable?

J Neurol 2020 May 1;267(5):1464-1475. Epub 2020 Feb 1.

1st Department of Neurology, Eginition Hospital, National and Kapodistrian University of Athens, 74 Vas. Sofias Av., 11528, Athens, Greece.

Background: Numerous cross-sectional studies report cognitive impairment in multiple sclerosis (MS), but longitudinal studies with sufficiently long-term follow-up are scarce.

Objective: We aimed to investigate the cognitive 10-year course of a cohort of MS patients.

Methods: 59 patients with clinically isolated syndrome (CIS) or relapsing-remitting (RR) MS were evaluated with Rao's Brief Repeatable Battery of Neuropsychological Tests at baseline and follow-up (at least 10 years later). They constituted 47.2% of 124 consecutive CIS and RRMS patients originally evaluated at baseline. Patients assessed at follow-up were well matched for baseline clinical characteristics with dropouts.

Results: The proportion of MS patients with overall cognitive impairment was increased by 10% within the 10-year period. When grouped on the basis of impairment in specific cognitive domains at baseline, patients originally impaired showed improvement at follow-up, while the opposite trend was observed for patients non-impaired at first assessment. A detailed case-by-case investigation revealed mixed evolution patterns, several patients fail in fewer domains at follow-up compared to baseline or failing at different domains at follow-up compared to baseline.

Conclusions: This study suggests a more fluid picture for the evolution of cognitive function in a subgroup of MS patients and contradicts the concept of an inevitable, progressively evolving "dementia".
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http://dx.doi.org/10.1007/s00415-020-09720-8DOI Listing
May 2020

Pesticide exposure and cognitive function: Results from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD).

Environ Res 2019 Oct 13;177:108632. Epub 2019 Aug 13.

Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus. Electronic address:

Background: Results from studies to date, regarding the role of chronic pesticide exposure on cognitive function remain contradictory.

Objective: To investigate the relationship between self-reported pesticide exposure and cognitive function.

Methods: Data from a population-based cohort study of older adults (HEllenic Longitudinal Investigation of Aging and Diet) in Greece was used. Pesticide exposure classification was based on 1) living in areas that were being sprayed; 2) application of spray insecticides/pesticides in their gardens; and 3) occupational application of sprays. Associations between z-scores of cognitive performance and self-reported pesticide exposure were examined with linear regression analyses. Adjusted models were applied, for all analyses.

Results: Non-demented individuals who reported that they had been living in areas near sprayed fields, had poorer neuropsychological performance, compared to those who had never lived in such areas. Sub-analyses revealed poorer performance in language, executive and visual-spatial functioning, and attention. These associations remained after a sensitivity analysis excluding subjects with mild cognitive impairment.

Conclusion: Self-reported exposure to pesticides was negatively associated with cognitive performance.
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http://dx.doi.org/10.1016/j.envres.2019.108632DOI Listing
October 2019

The Modality Effect on Delayed Free Recall in Non-demented Patients With Mild Parkinson's Disease Progression.

Front Aging Neurosci 2019 23;11:189. Epub 2019 Jul 23.

First Department of Neurology, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.

: The modality effect plays the central role in learning and memory functions. Retrieval failure constitutes a common memory impairment that occurs among patients with Parkinson's disease (PD). However, little knowledge exists about the relation between modality effect and delayed recall impairment in PD. The primary goal of this study was to compare delayed free recall performance between three different memory modalities (verbal, visual, and cross visual-verbal) in a sample of non-demented patients with mild PD progression. The secondary goal was to explore the frequency of deficient performance on the basis of normative comparisons on each of the three delayed free-recall measures. : A total of 71 non-demented patients with mild PD progression were recruited for the administration of the Montreal Cognitive Assessment (MoCA), the Rey Auditory Verbal Learning Test (RAVLT), the Rey Osterrieth Complex Figure Test (ROCFT), and the Greek Version of Face-Name Associative Memory Examination (GR-FNAME12). : The percentages of deficient-performances for the three delayed free recall measures were 45.1% (32/71), 39.4% (28/71) and 31% (22/71) for the GR-FNAME12, ROFCT and RAVLT, respectively. The results indicated no significant difference between performances of the GR-FNAME12 and ROCFT, both of which were significantly lower than performance on the RAVLT. : In conclusion, delayed free recall appears to be more severely affected in the cross visual-verbal and visual memory modalities than in verbal-memory modalities in the early phase of PD progression.
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http://dx.doi.org/10.3389/fnagi.2019.00189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6664063PMC
July 2019

The performance of patients with Parkinson's disease on the Face-Name Associative Memory Examination.

Neurol Sci 2019 Feb 12;40(2):405-407. Epub 2018 Sep 12.

First Department of Neurology, Aeginition Hospital, National and Kapodistrian University of Athens, 72-74, Vas., Sophias Avenue, 115 28, Athens, Greece.

In this study, we examined the performance of patients with Parkinson's disease (PD) with different cognitive profiles on the Face-Name Associative Memory Examination (FNAME). We evaluated 71 patients with a comprehensive neuropsychological battery. The results revealed that the group with executive and additional visuospatial deficits demonstrated significantly lower scores on FNAME. This finding indicates the possible clinical utility of FNAME for screening patients with PD with distinct cognitive profiles. Further longitudinal studies are needed to consider the prognostic adequacy of FNAME in detecting high-risk Parkinson's disease dementia (PDD).
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http://dx.doi.org/10.1007/s10072-018-3560-6DOI Listing
February 2019

Hippocampal structural and functional integrity in multiple sclerosis patients with or without memory impairment: a multimodal neuroimaging study.

Brain Imaging Behav 2019 Aug;13(4):1049-1059

1st Department of Neurology, Aeginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

The increasing evidence for a pure amnestic-like profile in multiple sclerosis (MS) introduces the role of hippocampal formation in MS episodic memory function. The aim of the present study was to investigate structural and functional hippocampal changes in mildly-disabled MS patients with and without memory impairment. Thirty-one MS patients with or without memory impairment and 16 healthy controls (HC) underwent MRI in a 3.0 T MRI scanner. Patients were categorized as memory preserved (MP) and memory impaired (MI) based on verbal and visual memory scores extracted from the Brief Repeatable Neuropsychological Battery. The acquisition protocol included high-resolution 3D-T1-weighted, diffusion weighted imaging and echo-planar imaging sequences for the analysis of hippocampal gray matter (GM) density, perforant pathway area (PPA) tractography, and hippocampal functional connectivity (FC), respectively. Compared to HC, we found decreased left and bilateral hippocampal GM density in MP and MI patients, respectively, decreased fractional anisotropy and increased radial diffusivity on left PPA in MI patients, and reduced FC in MI between left hippocampus and left superior frontal gyrus, precuneus/posterior cingulated cortex and lateral occipital gyrus/angular gyrus. The only differences between MP and MI were found in FC. Specifically, MP patients showed FC changes between left hippocampus and right temporo-occipital fusiform/lingual gyrus (increased FC) as well as supramarginal gyrus (decreased FC). In conclusion, we highlight the early detection of structural hippocampal changes in MS without neuropsychologically-detected memory deficits and decreased hippocampal FC in MS patients with impaired memory performance, when both GM density and PPA integrity are affected.
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http://dx.doi.org/10.1007/s11682-018-9924-yDOI Listing
August 2019

Development of the Greek version of the Face Name Associative Memory Exam (GR-FNAME12) in cognitively normal elderly individuals.

Clin Neuropsychol 2018 Jan-Dec;32(sup1):152-163. Epub 2018 Jul 2.

a First Department of Neurology , National and Kapodistrian University of Athens, Aeginition Hospital , Athens , Greece.

Objective: The Face-Name Associative Memory Examination (FNAME) is a cross-modal associative memory test with a high sensitivity for detecting Alzheimer's disease-related subtle memory problems at an early preclinical stage. The present study examined the psychometric characteristics of a Greek version of the short form of FNAME (GR-FNAME12) to evaluate the contribution of demographic characteristics, report the range of performance within our sample, and estimate regression-based norms in cognitively normal elderly individuals.

Method: In all, 216 cognitively normal elderly individuals were recruited and were administered a version of the short form of the FNAME (GR-FNAME12) that was culture and language specific to Greek-speaking individuals and developed for this study.

Results: The construct validity of GR-FNAME12 was determined using principal component analysis thereby revealing two factors: face-name and face-occupation. These match the original version of the test. A significant positive correlation between GR-FNAME12 and two traditional memory measures - the RAVLT and the ROCFT - supported convergent validity. Test-retest reliability was computed for 32 participants. Multiple regression analyses showed that only age and not education or gender significantly predicted performance on the GR-FNAME12. We also estimated regression-based norms for the GR-FNAME12 scales.

Conclusion: It was found that the Greek version of the FNAME12 had adequate psychometric properties, and could be administered to Greek-speaking individuals for clinical and research purposes.
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http://dx.doi.org/10.1080/13854046.2018.1495270DOI Listing
September 2019

Structural MRI Correlates of Cognitive Event-Related Potentials in Multiple Sclerosis.

J Clin Neurophysiol 2018 Sep;35(5):399-407

First Department of Neurology, Aeginition Hospital, Faculty of Medicine, National Kapodistrian University of Athens, Athens, Greece.

Purpose: Cognitive impairment in multiple sclerosis has been associated with cognitive event-related potentials and MRI abnormalities. This study aims to explore for the first time the association between P300 and MRI in multiple sclerosis.

Methods: Fifty-eight relapsing-remitting patients (41.5 ± 10.5 years old, 41 women, disease duration 139.7 ± 84.9 months) and 51 healthy controls were used. Visual P300 responses and a set of 2- or 3-dimensional MRI indices were obtained. Neuropsychological testing and psychological evaluations were also performed.

Results: Multiple sclerosis patients had significantly lower P300 amplitude and more prolonged P300 latencies and reaction times than healthy controls. In total, 67.2% of patients were identified with abnormal P300 response. These patients had greater disability and physical fatigue and had lower visuospatial memory scores than those with normal P300 response. Abnormally low P300 amplitude was associated with lower peripheral gray matter volume and was correlated only with normalized frontal horn width and normalized brain volume, after adjusting for age and education. The moderating role of brain reserve was also documented.

Conclusions: P300 event-related potential was related to both linear and volumetric MRI markers. Future studies should expand these results in other disease types and longitudinally. Event-related potentials could serve as an ancillary tool for cognitive assessment in multiple sclerosis.
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http://dx.doi.org/10.1097/WNP.0000000000000473DOI Listing
September 2018

Structural MRI correlates of cognitive function in multiple sclerosis.

Mult Scler Relat Disord 2018 Apr 6;21:1-8. Epub 2018 Feb 6.

1st Department of Neurology, Aeginition Hospital, Faculty of Medicine, National Kapodistrian University of Athens, Vas. Sofias Ave. 72-74, GR-11528 Athens, Greece.

Background: Cognitive impairment (CI) has been associated with numerous magnetic resonance imaging (MRI) indices in multiple sclerosis (MS) patients. In this study we investigated the association of a large set of 2D and 3D MRI markers with cognitive function in MS.

Methods: A sample of 61 RRMS patients (mean age 41.8 ± 10.6 years old, 44 women, mean disease duration 137.9 ± 83.9 months) along with 51 age and gender matched healthy controls was used in this cross-sectional study. Neuropsychological and other tests, along with a large set of 2D/3D MRI evaluations were made.

Results: 44.3% of patients had CI. CI patients had more disability, physical fatigue than non-CI patients and more psychological distress than non-CI patients and HCs. Also, CI patients had significantly larger third ventricle width and volume, smaller coprus callosum index and larger lesion volume than non-CI patients. These MRI markers also significantly predicted cognitive scores after adjusting for age and education, explaining about 30.6% of the variance of the total cognitive score.

Conclusions: Selected linear and volumetric MRI indices predict cognitive function in MS. Future studies should expand these results by exploring longitudinal changes and producing normative data.
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http://dx.doi.org/10.1016/j.msard.2018.02.003DOI Listing
April 2018

Endogenous sex hormones and memory performance in middle-aged Greek women with subjective memory complaints.

Neurol Sci 2018 Feb 16;39(2):259-266. Epub 2017 Nov 16.

2nd Department of Obstetrics and Gynecology, Aretaieio Hospital, National and Kapodistrian University of Athens, Athens, Greece.

The changing hormonal milieu during the menopausal transition may contribute to the development of memory disorders. We aimed to assess the association of sex hormones with memory function in a sample of Greek middle-aged women. This pilot study included 44 women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory test (BVMT), and the verbal digits backwards test (VSPAN), to assess verbal, visuospatial, and working memory performance, respectively. Menopausal symptoms were assessed using the Green Climacteric Scale. VSPAN backwards scores were positively associated with log-transformed free androgen index (logFAI), in models adjusted for age, education, log-transformed free estrogen index (logFEI), hypertension, and the intensity of menopausal symptoms. BVMT total scores were predicted by logFAI (b-coefficient = 0.424, p value = 0.002), education, and combined climacteric symptomatology, in a model adjusted for age, logFEI, and hypertension. Women with circulating estradiol above the median value of 10 pg/mL had better total HTLV total scores compared to women with estradiol values below the median (HTLV total scores, estradiol ≤ 10 pg/mL vs. > 10 pg/mL: 24.2 ± 3.6 vs. 30.0 ± 7.9, p value = 0.007 unadjusted). This association was affected by education and remained independent of menopausal symptoms and testosterone levels, education, and hypertension (model R = 22.3%; b-coefficient = 0.318, p value = 0.024). Endogenous total estradiol is associated with verbal episodic memory, while logFAI is associated with working memory performance and visuospatial episodic memory in this sample of postmenopausal women. These associations were not influenced by age, education, or menopausal symptoms. Larger studies are necessary to evaluate the significance of our findings.
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http://dx.doi.org/10.1007/s10072-017-3165-5DOI Listing
February 2018

Investigating the neuroanatomical substrate of pathological laughing and crying in amyotrophic lateral sclerosis with multimodal neuroimaging techniques.

Amyotroph Lateral Scler Frontotemporal Degener 2018 02 15;19(1-2):12-20. Epub 2017 Oct 15.

a First Department of Neurology , Aeginition Hospital, Medical School, National & Kapodistrian University of Athens , Athens , Greece.

Objective: Pathological laughing and crying (PLC) is common in several neurological and psychiatric diseases and is associated with a distributed network involving the frontal cortex, the brainstem and cortico-pontine-cerebellar circuits. By applying multimodal neuroimaging approach, we examined the neuroanatomical substrate of PLC in a sample of patients with amyotrophic lateral sclerosis (ALS).

Methods: We studied 56 non-demented ALS patients and 25 healthy controls (HC). PLC was measured in ALS using the Center of Neurologic Study Lability Scale (CNS-LS; cutoff score: 13). All participants underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging at 3T. Voxel-based morphometry and tract-based spatial-statistics analysis was used to examine gray matter (GM) and white matter (WM) differences between ALS patients with and without PLC (ALS-PLC and ALS-nonPLC, respectively). Comparisons were restricted to regions with detected differences between ALS and HC, controlling for age, gender, total intracranial volume and depressive symptoms.

Results: In regions with significant differences between ALS and HC, ALS-PLC patients showed decreased GM volume in left orbitofrontal cortex, frontal operculum, and putamen and bilateral frontal poles, compared to ALS-nonPLC. They also had decreased fractional anisotropy in left cingulum bundle and posterior corona radiata. WM abnormalities were additionally detected in WM associative and ponto-cerebellar tracts (using a more liberal threshold).

Conclusions: PLC in ALS is driven by both GM and WM abnormalities which highlight the role of circuits rather than isolated centers in the emergence of this condition. ALS is suggested as a useful natural experimental model to study PLC.
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http://dx.doi.org/10.1080/21678421.2017.1386689DOI Listing
February 2018

Verbal and Figural Fluency in Temporal Lobe Epilepsy: Does Hippocampal Sclerosis Affect Performance?

Cogn Behav Neurol 2017 06;30(2):48-56

*Neuropsychological Laboratory, 1st Department of Neurology †1st Department of Neurology; and ‡1st Department of Psychiatry, Aeginition Hospital §2nd Department of Neurology and ¶2nd Department of Radiology, Attikon Hospital ∥1st Department of Neurosurgery, Evangelismos Hospital; Medical School, National & Kapodistrian University, Athens, Greece.

Background And Objectives: Clinicians commonly use verbal and nonverbal measures to test fluency in patients with epilepsy, either during routine cognitive assessment or as part of pre- and postsurgical evaluation. We hypothesized that patients with mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis would perform worse than patients with lateral TLE in both verbal and design fluency.

Methods: We assessed semantic, phonemic, and nonverbal fluency in 49 patients with TLE: 31 with lateral TLE and 18 with mesial TLE plus hippocampal sclerosis. We also gave non-fluency cognitive measures: psychomotor speed, attentional set shifting, selective attention, abstract reasoning, verbal and visual episodic memory, and incidental memory.

Results: Patients with mesial TLE performed significantly worse on figural fluency than patients with lateral TLE. Even though group differences on verbal fluency measures were not significant, the patients with mesial TLE had a pattern of poorer performance. The patients with mesial TLE scored significantly worse on measures of selective attention, verbal episodic memory, and incidental memory.

Conclusions: Our study underlines differences in cognitive function between patients with mesial and lateral TLE, particularly in figural fluency. Although we cannot directly assess the role of the hippocampus in cognitive aspects of creative and divergent thinking related to figural fluency, the cognitive discrepancies between these two TLE groups could be ascribed to the mesial TLE hippocampal pathology shown in our study and addressed in the literature on hippocampal involvement in divergent thinking. Our findings could benefit cognitive rehabilitation programs tailored to the needs of patients with TLE.
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http://dx.doi.org/10.1097/WNN.0000000000000123DOI Listing
June 2017

Gray matter and white matter changes in non-demented amyotrophic lateral sclerosis patients with or without cognitive impairment: A combined voxel-based morphometry and tract-based spatial statistics whole-brain analysis.

Brain Imaging Behav 2018 Apr;12(2):547-563

First Department of Neurology, Aeginition Hospital, Medical School, National & Kapodistrian University, Athens, Greece.

The phenotypic heterogeneity in amyotrophic lateral sclerosis (ALS) implies that patients show structural changes within but also beyond the motor cortex and corticospinal tract and furthermore outside the frontal lobes, even if frank dementia is not detected. The aim of the present study was to investigate both gray matter (GM) and white matter (WM) changes in non-demented amyotrophic lateral sclerosis (ALS) patients with or without cognitive impairment (ALS-motor and ALS-plus, respectively). Nineteen ALS-motor, 31 ALS-plus and 25 healthy controls (HC) underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging on a 3 T MRI scanner. Voxel-based morphometry and tract-based spatial-statistics analysis were performed to examine GM volume (GMV) changes and WM differences in fractional anisotropy (FA), axial and radial diffusivity (AD, RD, respectively). Compared to HC, ALS-motor patients showed decreased GMV in frontal and cerebellar areas and increased GMV in right supplementary motor area, while ALS-plus patients showed diffuse GMV reduction in primary motor cortex bilaterally, frontotemporal areas, cerebellum and basal ganglia. ALS-motor patients had increased GMV in left precuneus compared to ALS-plus patients. We also found decreased FA and increased RD in the corticospinal tract bilaterally, the corpus callosum and extra-motor tracts in ALS-motor patients, and decreased FA and increased AD and RD in motor and several WM tracts in ALS-plus patients, compared to HC. Multimodal neuroimaging confirms motor and extra-motor GM and WM abnormalities in non-demented cognitively-impaired ALS patients (ALS-plus) and identifies early extra-motor brain pathology in ALS patients without cognitive impairment (ALS-motor).
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http://dx.doi.org/10.1007/s11682-017-9722-yDOI Listing
April 2018

Memory-related white matter tract integrity in amyotrophic lateral sclerosis: an advanced neuroimaging and neuropsychological study.

Neurobiol Aging 2017 01 28;49:69-78. Epub 2016 Sep 28.

First Department of Neurology, Aeginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

We aimed to investigate structural changes in vivo in memory-related white matter tracts (i.e., perforant pathway zone [PPZ]; uncinate fasciculus [UF]; fornix) using diffusion tensor tractography and evaluate possible associations with memory performance in nondemented patients with amyotrophic lateral sclerosis (ALS). Forty-two ALS patients and 25 healthy controls (HCs) underwent a 30-directional diffusion-weighted imaging on a 3T MR scanner, followed by tractography of PPZ, UF, and fornix and analysis of fractional anisotropy (FA), axial diffusivity and radial diffusivity (Dr). Patients were administered neuropsychological measures of verbal (list learning via Rey Auditory Verbal Learning Test [RAVLT] and prose memory via Babcock Story Recall Test) and nonverbal (Rey's Complex Figure Test) episodic memory. After correcting for multiple comparisons, ALS patients showed increased Dr in the left PPZ compared to HC. We then fitted a multivariate general linear model within ALS patients with neuropsychological measures as dependent variables and age, age, gender, verbal IQ, and diffusion tensor tractography metrics with at least medium effect size differences between ALS and HC as independent variables. We found that (1) left PPZ FA, gender, and verbal IQ contributed to RAVLT-Total Learning; (2) left PPZ FA, left UF Dr, and gender contributed to RAVLT-Immediate Recall; and (3) left PPZ FA and left UF axial diffusivity contributed to Babcock Story Recall Test-Immediate and Delayed Recall. Advanced neuroimaging techniques verified in this study previously reported neuropathological findings regarding PPZ degeneration in ALS. We also detected a unique contribution of microstructural changes in hippocampal and frontotemporal white matter tracts on patients' memory profile.
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http://dx.doi.org/10.1016/j.neurobiolaging.2016.09.014DOI Listing
January 2017

Determinants of stigma in a cohort of hellenic patients suffering from multiple sclerosis: a cross-sectional study.

BMC Neurol 2016 Jul 13;16:101. Epub 2016 Jul 13.

1st Department of Psychiatry, Medical School of National and Kapodistrian University of Athens, Aeginition Hospital, Vas.Sophias ave 72-74, Athens, 115-28, Greece.

Background: Patients suffering from several neurologic disorders may bear the "stigma" of their disease, being disqualified from full social acceptance. Although stigma is considered to be present in Multiple Sclerosis (MS), the factors that influence its levels are ambiguous. Aim of our study was to examine, for the first time in the literature, the basic determinants of stigma in a Hellenic MS-patients cohort, as well as how stigma affects their Quality-of-Life (QoL) profiles.

Methods: Three hundred forty two patients were recruited in this study. Data collected concerned sociodemographic and disease-related variables, mental illness assessment, Multiple-Sclerosis-QoL-54 (MSQoL-54) and Stigma-Scale-for-Chronic-Illness-24 (SSCI-24) questionnaires. Potential determinants were evaluated with univariate statistical analyses for their contribution to total, internalized (inner-self derived) and externalized (society derived) stigma. Important findings were further evaluated on hierarchical regression models.

Results: Disability levels were found to be the most powerful predictor in all stigma categories, followed by the presence of mental illness. Working and caregiving status were also ascertained as determinants of internalized stigma. Stigma levels displayed strong negative correlation with all composites of MSQoL-54.

Conclusions: Stigma is present in the social environment of MS patients and was confirmed as a barrier (according to the International Classification of Functioning, Disability and Health), with detrimental effects on their QoL levels and functioning performances. Disability and mental illness were shown as the principal determinants of stigma, while financial characteristics were not as equally involved. Further validation of these results in other MS populations may provide safer conclusions, towards more efficacious patient-centered care outcomes.
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http://dx.doi.org/10.1186/s12883-016-0621-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944520PMC
July 2016

Preoperative neuropsychological presentation of patients with refractory frontal lobe epilepsy.

Acta Neurochir (Wien) 2016 06 2;158(6):1139-50. Epub 2016 Apr 2.

Department of Neurology, School of Medicine, University of Athens, Eginition Hospital, 11528, Athens, Greece.

Background: This study investigated whether certain cognitive deficits are associated with frontal lobe epilepsy (FLE) aiming to contribute with localization data to the preoperative assessment of epilepsy surgery candidates.

Methods: We evaluated 34 patients with refractory FLE, 37 patients with refractory medial temporal lobe epilepsy (MTLE), and 22 healthy individuals in attention, psychomotor speed, motor function, verbal memory span, verbal fluency, response inhibition/interference, concept formation and set shifting, anticipation and planning, global memory.

Results: Neuropsychological performances of FLE and MTLE were similar, with the only exception the WCST-number of categories index, measuring mental flexibility, in which MTLE patients performed significantly worse than FLE patients. Left-FLE patients presented more perseverative responding compared to both other patient groups and healthy controls (HCs), while left-MTLE patients showed worse sorting abilities than the other epilepsy groups.

Conclusions: Our findings suggest a weak cognitive differentiation between FLE and MTLE, probably attributed to the intricate nature of fronto-temporal connectivity frequently resulting in overlapping deficits as well as the confounding effects of seizure-related variables. In clinical practice, a highly individualized (idiographic) neuropsychological approach along with the inclusion of concurrent EEG recordings (e.g., interictal coupling) may be of help for neuropsychologists in identifying FLE patients from those with medial temporal pathology presenting frontal dysfunction as a secondary cognitive symptom.
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http://dx.doi.org/10.1007/s00701-016-2786-4DOI Listing
June 2016

Frontotemporal Dysfunction in Amyotrophic Lateral Sclerosis: A Discriminant Function Analysis.

Neurodegener Dis 2016 16;16(3-4):140-6. Epub 2015 Dec 16.

First Department of Neurology, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Background: There is growing evidence for extramotor dysfunction (EMd) in amyotrophic lateral sclerosis (ALS), with a reported prevalence of up to 52%.

Objective: In the present study, we explore the clinical utility of a brief neuropsychological battery for the investigation of cognitive, behavioral, and language deficits in patients with ALS.

Methods: Thirty-four consecutive ALS patients aged 44-89 years were tested with a brief neuropsychological battery, including executive, behavioral, and language measures. Patients were initially classified as EMd or non-EMd based on their scores on the frontal assessment battery (FAB).

Results: Between-group comparisons revealed significant differences in all measures (p < 0.01). Discriminant analysis resulted in a single canonical function, with all tests serving as significant predictors. This function agreed with the FAB in 13 of 17 patients screened as EMd and identified extramotor deficits in 2 additional patients. Overall sensitivity and specificity estimates against FAB were 88.2%.

Conclusions: We stress the importance of discriminant function analysis in clinical neuropsychological assessment and argue that the proposed neuropsychological battery may be of clinical value, especially when the option of extensive and comprehensive neuropsychological testing is limited. The psychometric validity of an ALS-frontotemporal dementia diagnosis using neuropsychological tests is also discussed.
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http://dx.doi.org/10.1159/000381186DOI Listing
December 2016

Central Nervous System Involvement as Relapse in Undiagnosed Whipple's Disease with Atypical Symptoms at Onset.

Open Neurol J 2015 26;9:21-3. Epub 2015 Jun 26.

Department of Neurology, Aeginition Hospital, Medical School, Athens National & Kapodistrian University, 72-74 Vas. Sofias Avenue, Athens, 115 28, Greece.

Whipple's disease (WD) is a rare systemic disease caused by the gram-positive bacillus Tropheryma Whipplei and mostly characterized by arthralgias, chronic diarrhea, weight loss, fever and abdominal pain. Central Nervous System involvement is not uncommon and it may precede other disease manifestations, appear after treatment and improvement of gastrointestinal signs or rarely be the only WD symptom. We report a case in a middle-aged male with unexplained neurological signs and symptoms which were presented as relapse of previously undiagnosed WD with atypical symptoms at onset. After diagnosis confirmation, the patient was appropriately treated which resulted in improvement of major symptoms.
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http://dx.doi.org/10.2174/1874205X01509010021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503830PMC
July 2015

Clinical and cognitive implications of cerebrospinal fluid oligoclonal bands in multiple sclerosis patients.

Neurol Sci 2015 Nov 1;36(11):2053-60. Epub 2015 Jul 1.

First Department of Neurology, Medical School, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.

The presence of cerebrospinal fluid oligoclonal bands (CSF-OCB) in Caucasian patients with multiple sclerosis (MS) is supportive of diagnosis, though the relation with patients' clinical and specifically cognitive features has never been established or thoroughly examined. Thus, we investigated the clinical and for the first time the cognitive profile of MS patients in relation to CSF-OCB. We studied 108 patients with and without OCB and recorded demographic characteristics and detailed clinical data. A comprehensive neuropsychological battery covering different cognitive domains (attention/processing speed, memory, perception/constructions, reasoning, executive functions) was administered to MS patients and 142 demographically related healthy controls (HC). We did not find any significant differences between patients with and without OCB on demographic and clinical parameters (p > 0.05), including subtype and brain neuroimaging findings. Results revealed significantly higher cognitive scores in HC compared to both OCB subgroups, with more widespread cognitive changes in patients with OCB. Analysis between OCB subgroups showed significantly worse performance in patients with OCB on visual memory (Rey's complex figure test-recall; p = 0.006). Concluding, the presence of CSF-OCB in our MS patients tends to be related to more widespread cognitive changes, specifically worse visual memory. Future longitudinal studies in different populations are warranted to better clarify the clinical and cognitive characteristics related to CSF-OCB which could serve as early biomarker in disease monitoring.
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http://dx.doi.org/10.1007/s10072-015-2303-1DOI Listing
November 2015

Derived Trail Making Test indices: demographics and cognitive background variables across the adult life span.

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2015 23;22(6):667-78. Epub 2015 Mar 23.

a Neuropsychological Laboratory, A' Department of Neurology, Aeginition Hospital, Medical School , National & Kapodistrian University , Athens , Greece.

We examined the contribution of demographics and cognitive background variables (processing speed, visuospatial skill, working memory, and interference control) on derived Trail Making Test (TMT) scores in a large sample of Greek healthy participants. We included 775 participants and administered the TMT (TMT-A and TMT-B) and the Wechsler Intelligence Adult Scale (WAIS). Direct (TMT-A & TMT-B time-to-completion) and derived [difference TMT-(B - A) & ratio TMT-(B/A)] scores were calculated. Demographics (age, age(2), education, and gender) and WAIS Full Intelligence Quotient significantly predicted the direct TMT-A (R(2) = 0.426) and TMT-B (R(2) = 0.593) scores and to a lesser extent, the derived TMT-(B - A) (R(2) = 0.343) and TMT-(B/A) (R(2) = 0.088) scores. In a subsample of 537 healthy participants who also completed the Stroop Neuropsychological Screening Test (SNST), demographics (age and education), WAIS Digit Symbol, Block Design, Arithmetic, and SNST accounted for 44.8% and 59.7% of the variance on TMT-A and TMT-B, and 32.5% and 9.6% of the variance on TMT-(B - A) and TMT-(B/A), respectively. We found minimal influence of Block Design and Arithmetic on TMT-(B - A) and an absence of significant influence of any cognitive variable on TMT-(B/A) score. Concluding, derived TMT scores are suggested as indices to detect impairment in cognitive flexibility across the adult life span, since they minimize the effect of demographics and other cognitive background variables.
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http://dx.doi.org/10.1080/13825585.2015.1027650DOI Listing
May 2016

Auditory event-related potentials (P300) and mesial temporal sclerosis in temporal lobe epilepsy patients.

Epileptic Disord 2014 Mar;16(1):67-73

University of Athens, 1st Neurological Clinic.

Aims: To investigate the role of centrally recorded P300 in patients suffering from mesial temporal sclerosis-temporal lobe epilepsy (MTS-TLE).

Methods: Sixteen patients (3 men and 13 women; median age: 32.5 years old) suffering from TLE with MTS and 43 healthy controls (12 men and 31 women; median age: 35 years old) participated in the study. P300 was elicited using an auditory two-stimulus oddball paradigm. In order to address the aim of the study, we adopted two statistical approaches; hierarchical linear regression analyses and ROC curves.

Results: After adjusting for age, MTS patients had a mean reduction of P300 amplitude by 6.93 μV and a mean increase of P300 latency by 38.78 ms, compared to controls. Age and MTS-TLE status accounted for 32 and 16% of the variance of latency and amplitude, respectively. Diagnostic analyses to detect MTS-TLE status revealed a sensitivity and specificity of 88 and 65% for amplitude and 81 and 70% for latency, respectively. No association between duration of disease and P300 characteristics were found.

Conclusions: This study, along with other studies, contributes to our understanding and clinical significance of centrally recorded P300s in MTS-TLE patients. Future studies should focus on the association of these P300s with cognition in such patients.
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http://dx.doi.org/10.1684/epd.2014.0631DOI Listing
March 2014

Neurocognitive impairment in Whipple disease with central nervous system involvement.

Cogn Behav Neurol 2014 Mar;27(1):51-6

*Neuropsychological Laboratory, First Department of Neurology †First Department of Neurology, Eginition Hospital, Medical School, National & Kapodistrian University, Athens, Greece.

Young-onset dementias pose a major challenge to both clinicians and researchers. Cognitive decline may be accompanied by systemic features, leading to a diagnosis of "dementia plus" syndromes. Whipple disease is a rare systemic illness characterized by arthralgias, chronic diarrhea, weight loss, fever, and abdominal pain. Central nervous system involvement, including severe cognitive deterioration, may precede systemic manifestations, appear during the course of the disease, or even be the only symptom. We report a previously highly functional 48-year-old man whom we first suspected of having early-onset neurodegenerative dementia but then diagnosed with Whipple disease based on a detailed clinical and laboratory evaluation. Initial neuropsychological evaluation revealed marked impairment in the patient's fluid intelligence and severe cognitive deficits in his information processing speed, complex attention, memory, visuomotor and construction dexterities, problem solving, and executive functions. At neuropsychological follow-up 21 months later, his information processing speed had improved only slightly and deficits persisted in his other cognitive functions. Repeat brain magnetic resonance imaging at that time showed that he had responded to antibiotic treatment. Because Whipple disease can cause young-onset "dementia plus" syndromes that may leave patients with neurocognitive deficits even after apparently successful treatment, we recommend comprehensive neuropsychological assessment for early detection of residual and reversible cognitive processes and evaluation of treatment response.
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http://dx.doi.org/10.1097/WNN.0000000000000016DOI Listing
March 2014

Uncinate fasciculus microstructure and verbal episodic memory in amyotrophic lateral sclerosis: a diffusion tensor imaging and neuropsychological study.

Brain Imaging Behav 2014 Dec;8(4):497-505

First Department of Neurology, Aeginition Hospital, Medical School, National and Kapodistrian University, Athens, Greece,

The present study evaluates the integrity of uncinate fasciculus (UF) and the association between UF microstructure and verbal episodic memory (as one of the cognitive functions linked to UF) in non-demented patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI). We studied 21 patients with ALS and 11 healthy, demographically-comparable volunteers. Fractional anisotropy, apparent diffusion coefficient, axial and radial diffusivity were the DTI metrics examined. Episodic memory was evaluated with Babcock Story Recall Test and Rey Auditory Verbal Learning Test (RAVLT) for patients; measures of immediate and delayed recall and retention for both tests and sum of words recalled through five learning trials for RAVLT were considered. Patients with ALS showed significant bilateral reduction of axial diffusivity in the UF as compared to controls. Furthermore, there were several significant relations between various DTI metrics (mostly in left hemisphere) and memory measures (specifically for the RAVLT). UF microstructural changes may contribute to ALS-related memory impairment, with word-list learning performance relying more upon the integrity of frontal and temporal connections than memory components associated with story recall.
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http://dx.doi.org/10.1007/s11682-013-9271-yDOI Listing
December 2014

Simulating memory outcome before right selective amygdalohippocampectomy.

Neuropsychol Rehabil 2013 26;23(3):401-15. Epub 2013 Feb 26.

Department of Neurosurgery, School of Medicine, Evangelismos Hospital, University of Athens, Greece.

In this paper we present the case of a left-sided speech dominant patient with right medial temporal sclerosis (RMTS) and pharmacoresistant epilepsy who showed improved verbal memory during intracarotid amobarbital test (IAT) at his right hemisphere as compared with his own performance before the drug injection (baseline), as well as after right selective amygdalohippocampectomy. We suggest that the defective verbal memory shown by this patient is due to abnormal activity of his right hippocampus that interfered with the function of his left hippocampus. This hypothesis was demonstrated by the fact that disconnection of the two hippocampi, either by anesthetisation or by resection of the right hippocampus, disengaged the left hippocampus and, consequently improved its function. This paper main objective is twofold: first to contribute to the field of neuropsychology of epilepsy surgery by emphasising on postoperative memory outcomes in right medial temporal lobe epilepsy (RMTLE) patients, particularly those undergoing amygdalohippocampectomy, as the pattern of memory changes after resection of the right temporal lobe is less clear; second, by focusing on memory performance asymmetries during IAT, and comparatively considering them with neuropsychological memory performance, because of their possible prognostic-simulating value.
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http://dx.doi.org/10.1080/09602011.2013.772065DOI Listing
December 2013

The role of working memory and information processing speed on wisconsin card sorting test performance in Parkinson disease without dementia.

J Geriatr Psychiatry Neurol 2012 Dec 7;25(4):215-21. Epub 2012 Dec 7.

Postgraduate Program of Clinical Neuropsychology, Medical School, National & Kapodistrian University of Athens, and First Department of Neurology, Eginition Hospital, Athens, Greece.

Introduction: Wisconsin Card Sorting Test (WCST) performance is often compromised in Parkinson disease (PD).

Objective: We aimed to investigate (a) the role of working memory (WM) and information processing speed (IPS) in the WCST performance of PD without dementia and (b) the profile of PD without dementia optimal WCST performance.

Methods: 73 nondemented patients with PD were examined in WCST, WM (Digit Span Backwards [DSPANB] and Arithmetic subscale, Wechsler Adult Intelligence Scale [WAIS]), and IPS (Digit Symbol subscale-WAIS and Trail Making Test, part A [TMT-A]) and compared to a group of 48 healthy participants. The group with PD was further divided into 2 subgroups on the basis of their WCST performance, number of categories achieved (CAT):0-2 and CAT:3-6, and comparisons were performed.

Results: The DSPANB correlated significantly and was the only neuropsychological variable that significantly contributed to the WCST perseverative errors (WPERRORS) performed by the PD group. Differences in the cognitive performance between CAT:3-6 and CAT:0-2 PD subgroups were no longer significant after controlling for age and general level of intelligence (full IQ [FIQ]). Age and FIQ significantly contributed to the WPERRORS performed by CAT:3-6 PD subgroup, while DSPANB was the only variable that significantly contributed to their WCST overall performance.

Conclusions: Our findings address the relationship between WM and inflexible behavior exhibited by PD without dementia, argue for the importance of lower age, higher education, and level of intelligence for the successful performance on WCST; yet, the differences in cognitive performance regardless of the duration of illness within our patients with PD provide support to cognitive reserve concept.
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http://dx.doi.org/10.1177/0891988712466456DOI Listing
December 2012

Trail Making Test error analysis in classic motor neuron disease.

Neurol Sci 2013 Aug 18;34(8):1367-74. Epub 2012 Nov 18.

Neuropsychological Lab, A' Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University, 72-74 Vas. Sofias Avenue, 115 28, Athens, Greece.

The use of non-traditional scores in neuropsychological assessment allows for pattern analysis of test performance, commonly referred to as Quantified Process Approach (QPA). In the present study, the QPA was taken to study error rates on the Trail Making Test (TMT) in 26 non-demented patients with classic motor neuron disease (cMND), who commonly present with impaired cognitive flexibility, and 26 matched healthy controls. Between-group comparisons revealed that cMND patients exhibited higher total error rates on the TMT Part B (TMT-B) relative to controls (p < 0.001), though no significant associations were noted between TMT errors and measures of attention and executive function obtained using the Stroop Neuropsychological Screening Test, the Wechsler Adult Intelligence Scale Digit Symbol and Digit Span subtests and the Wisconsin Card Sorting Test. Moreover, the percentage of cMND patients with normal TMT-B time-to-completion who committed at least one error (either sequential or perseverative errors) in TMT-B was significantly higher compared to controls (p = 0.005). These findings suggest that error analysis using the QPA may increase the clinical utility of TMT and should be considered in addition to time-to-completion scores, in the neuropsychological assessment of patients with cMND.
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http://dx.doi.org/10.1007/s10072-012-1243-2DOI Listing
August 2013

Monosymptomatic clinically isolated syndrome with sudden sensorineural hearing loss: case report and critical review of the literature.

Neurologist 2012 Sep;18(5):302-5

A' Department of Neurology, Medical School, National & Kapodistrian University of Athens, Aeginition Hospital, Athens, Greece.

Introduction: Isolated cranial nerve involvement is rare in patients with multiple sclerosis (10.4%) and extremely rare is an eighth nerve palsy, especially in the context of a clinically isolated syndrome (<1%).

Case Report: A 34-year-old male presented with a history of left-sided tinnitus and sudden sensorineural hearing loss (SSNHL). Magnetic resonance imaging of the brain revealed >9, nonenhancing periventricular and corpus callosum lesions. Brainstem auditory evoked potentials were abnormal, ipsilateral to the affected ear, consistent with the presumed underlying demyelinating pathology. Visual evoked potentials showed bilateral prolonged P100 latencies. Oligoclonal bands were not detected in the cerebrospinal fluid, but IgG index was marginally elevated. After administration of corticosteroids, the patient recovered auditory function over a several month period.

Conclusions: This report describes a case of SSNHL in the context of magnetic resonance imaging of the brain and electrophysiological findings consistent with a demyelinating etiology. SSNHL is a rare and possibly underrecognized manifestation of clinically isolated syndrome.
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http://dx.doi.org/10.1097/NRL.0b013e3182675479DOI Listing
September 2012

Selective attention and the three-process memory model for the interpretation of verbal free recall in amyotrophic lateral sclerosis.

J Int Neuropsychol Soc 2012 Sep 7;18(5):809-18. Epub 2012 Jun 7.

Postgraduate Program in Clinical Neuropsychology, Medical School, National and Kapodistrian University, Athens, Greece.

The present study investigates selective attention and verbal free recall in amyotrophic lateral sclerosis (ALS) and examines the contribution of selective attention, encoding, consolidation, and retrieval memory processes to patients' verbal free recall. We examined 22 non-demented patients with sporadic ALS and 22 demographically related controls using Stroop Neuropsychological Screening Test (SNST; selective attention) and Rey Auditory Verbal Learning Test (RAVLT; immediate & delayed verbal free recall). The item-specific deficit approach (ISDA) was applied to RAVLT to evaluate encoding, consolidation, and retrieval difficulties. ALS patients performed worse than controls on SNST (p < .001) and RAVLT immediate and delayed recall (p < .001) and showed deficient encoding (p = .001) and consolidation (p = .002) but not retrieval (p = .405). Hierarchical regression analysis revealed that SNST and ISDA indices accounted for: (a) 91.1% of the variance in RAVLT immediate recall, with encoding (p = .016), consolidation (p < .001), and retrieval (p = .032) significantly contributing to the overall model and the SNST alone accounting for 41.6%; and (b) 85.2% of the variance in RAVLT delayed recall, with consolidation (p < .001) and retrieval (p = .008) significantly contributing to the overall model and the SNST alone accounting for 39.8%. Thus, selective attention, encoding, and consolidation, and to a lesser extent of retrieval, influenced both immediate and delayed verbal free recall. Concluding, selective attention and the memory processes of encoding, consolidation, and retrieval should be considered while interpreting patients' impaired free recall. (JINS, 2012, 18, 1-10).
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http://dx.doi.org/10.1017/S1355617712000562DOI Listing
September 2012