Background and Aims:

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia. However, clinical diagnosis can be challenging. Two toolkits have been deverloped to aid the clinical diagnosis of DLB: the Lewy Body Composite Risk Score (LBCRS) and the Assessment Toolkit for DLB (AT-DLB). The aim of the present study is to evaluate the diagnostic accuracy of these two questionnaires, as well as their capacity to enhance application and interpretation of the Consensus Criteria.

Methods:

In this study, LBCRS and AT-DLB were distributed to 135 Cognitive Decline and Dementia Centers (CDCD). We asked to administer the two questionnaires to all patients referred within the following three months, independently from the clinical diagnosis, and also to apply Consensus Criteria for DLB diagnosis, according to the results of each of the two toolkits, to all subjects.

Results:

A total of 23 Centers participated to the survey, and 2006 patients were enrolled. Diagnosis of dementia was not concordant in 152 (7.58%) subjects, who were excluded from the cohort. Of the 1854 remaining patients, 56.53% were female; the mean age was 75.06±14.58 years. LBCRS toolkit showed a good reliability (Cronbach-alpha=0.77), even when removing variables from the construct Conversely, AT-DLB toolkit Cronbach-alpha was 0.52 and, after the subtraction of the “cognitive fluctuation” criterion, was only 0.31.

Conclusions:

In a clinical setting, LBCRS questionnaire shows a better diagnostic accuracy for DLB diagnosis than AT-DLB questionnaire. Further investigations should focus on the assessment of LBCRS capacity to identify DLB patients at prodromal stages.

Background and Aims:

In pure-motor ALS patients, we recently observed that smaller volume of the left pallidum was related with impaired recognition of disgust. In the present study, we investigated the resting-state functional connectivity (RS-FC) of the pallidum in ALS, and the relationship between RS-FC changes and disgust recognition.

Methods:

19 pure-motor ALS patients and 52 matched healthy controls underwent RS functional MRI and a neuropsychological assessment including the Comprehensive Affect Testing System (CATS), investigating emotion recognition. A seed-based RS-FC analysis was run between the left and right pallidum and the rest of the brain, and compared between groups. Correlation analyses were run between the RS-FC significant changes and patients’ performance in recognizing disgust.

Results:

Compared to controls, ALS presented reduced RS-FC between bilateral pallidum and right superior and middle frontal gyri, and increased RS-FC between bilateral pallidum and left superior temporal and postcentral gyri, and left Rolandic operculum. Increased RS-FC was observed between left pallidum and left supramarginal gyrus and between right pallidum and contralateral insula and thalamus. In patients, lower performance in recognizing disgust was related with reduced RS-FC between bilateral pallidum and right middle and superior frontal gyri, and with increased RS-FC between bilateral pallidum and left postcentral gyrus and Rolandic operculum.

Conclusions:

In a cognitively unimpaired ALS patients, reduced pallidum-frontal RS-FC and increased pallidum-insular-thalamic RS-FC may suggest a fronto-striatal functional disconnection, which could have a role in the lower ability of patients in recognizing disgust.

Funding: Italian Ministry of Health (GR-2013-02357415); European Research Council (StG-2016_714388_NeuroTRACK).

Background and Aims:

To assess magnetic resonance imaging (MRI) alterations occurring in patients with trigeminal neuralgia and to explore the predictive ability of MRI for initial radiosurgical outcome and long-term pain relief/recurrence after Gamma Knife radiosurgery (GKSRS).

Methods:

Thirty patients with idiopathic or classical TN, who underwent GKSRS and were followed for at least 24 months, were retrospectively included. Pre-treatment structural MRI and pre- and serial, post-operative clinical features were investigated. Fifteen age- and sex-matched healthy controls were also enrolled. Cortical thickness and gray matter (GM) volumes were assessed in TN patients relative to controls, as well as between patient subgroups according to treatment outcomes (initial responders/non-responders, patients with pain recurrence/long-lasting pain relief at the last follow-up). Clinical and MRI predictors of treatment outcomes were explored.

Results:

Cortical thinning of temporal, prefrontal, cingulate, somatosensory and occipital areas bilaterally was found in TN patients relative to controls. Patients who experienced TN recurrence after initial pain relief were characterized by thicker parahippocampal and temporal cortices bilaterally and greater volume of right amygdala and hippocampus compared to patients with long-lasting pain relief. In TN patients, disease duration and baseline cortical thinning of right parahippocampal, left fusiform and middle temporal cortices were associated with poor outcome after GKSRS at the last follow-up (R²=0.57, p<0.001).

Conclusions:

The study provides novel insights into structural brain alterations of TN patients, which might contribute to disease development and pain maintenance.

Background and Aims:

C9orf72 mutation carriers with different neurological phenotypes, also in pre-symptomatic phases, show cortical atrophy in multiple different brain regions. Besides cortical thinning, also subcortical structureshave been found to be altered, both in C9orf72 carriers and in wild-type patients.

The aim of this study is to assess cortical and subcortical alterations in a large sample of mutation carriers and matched wild-type ALS patients.

Methods:

We paired 24 C9orf72 positive (C9orf72+) ALS patients with 24 C9orf72 negative (C9orf72-) ALS patients. They underwent 1.5T MRI assessment, performing 3D T1-weighted image scans. Vertex-wise between-group analyses for cortical thickness and subcortical region shape was performed to assess significant differences between C9orf72+ and C9orf72- groups.

Results:

The cortical vertex-wise showed a reduced cortical thickness in C9orf72+ patients in extended regions of the brain, in particular in: bilateral precentral and postcentral cortex, superior frontal gyrus, and precuneus, in left inferior temporal cortex, fusiform and parahippocampal gyri, lateral and medial orbital frontal cortex, posterior and rostral anterior cingulate, in right superior parietal and supramarginal cortex.

The subcortical vertex-wise showed an extensive reduced volume in C9orf72+ patients in bilateral thalamus, in bilateral caudate, and left putamen. On the other side, C9orf72- patients, in comparison to C9orf72+ patients, showed a selective reduction of volume in the anterior portion of left amygdala.

Conclusions:

Extensive brain atrophy is present in C9orf72+ patients when compared to C9orf72- patients with similar disease burden. Different extra-motor cortical regions and subcortical structures, such as the amygdala, could play a different role in ALS patients.

Background and Aims:

We aimed to assess cortical, subcortical and cerebellar grey matter (GM) atrophy using MRI in patients with disorders of the frontotemporal lobar degeneration (FTLD) spectrum with known genetic mutations.

Methods:

Sixty-six patients carrying FTLD-related mutations were enrolled, including 44 with pure motor neuron disease (MND) and 22 with frontotemporal dementia (FTD). Sixty-one patients with sporadic FTLD (sFTLD) matched for age, sex and disease severity with genetic FTLD (gFTLD) were also included, as well as 52 healthy controls. Voxel-based morphometry (VBM) was performed. GM volumes of subcortical and cerebellar structures were obtained.

Results:

Compared with controls, GM atrophy on VBM was greatest in genetic FTD, whereas sporadic MND (sMND) patients showed focal motor cortical atrophy. Patients carrying C9ORF72 and GRN mutations showed the most widespread cortical volume loss, in contrast with GM sparing in SOD1 and TARDBP. Globally, gFTLD patients showed greater atrophy of parietal cortices and thalami compared with sFTLD. In volumetric analysis, gFTLD patients showed volume loss compared with sFTLD in the caudate nuclei and thalami, especially comparing C9-MND with sMND. In the cerebellum, gFTLD patients showed greater atrophy of the right lobule VIIb than sFTLD. Thalamic volumes of gFTLD patients with a C9ORF72 mutation showed an inverse correlation with Frontal Behavioral Inventory scores.

Conclusions:

Measures of deep GM and cerebellar structural involvement may be useful markers of gFTLD, particularly C9ORF72-related disorders, regardless of the clinical presentation within the FTLD spectrum.

Study funding: Italian Ministry of Health (RF-2011-02351193; GR-2011-02351217; GR-2013-02357415) and the European Research Council (StG-2016_714388_NeuroTRACK).

Background and Aims:

To investigate cortical/subcortical and network functional alterations in PD patients with freezing of gait (PD-FoG), PD developing FoG (PD-FoG-converters) and PD not developing FoG (PD-non-converters) over one and two years.

Methods:

Thirty PD-FoG, 11 PD-FoG-converters and 11 PD-non-converters, age, sex, education, disease duration and severity matched, were followed for two years. Thirty age, sex and education matched healthy controls were included at baseline. Participants underwent clinical/MRI visits to evaluate cortical thickness, basal ganglia volumes and functional graph metrics at baseline and their changes over two years. Correlations between baseline MRIs and clinical worsening in PD groups and a ROC curve to investigate if any MRI measure at baseline could differentiate PD-FoG-converters and non-converters were run.

Results:

At baseline, PD-FoG had widespread cortical/subcortical atrophy, while PD-FoG-converters and non-converters showed atrophy in sensorimotor areas and basal ganglia. PD-FoG-converters relative to controls and PD-FoG showed higher global and parietal local efficiency and clustering coefficient. Over time, PD-FoG showed posterior cingulate atrophy but stable functional graph metrics. PD-FoG-converters accumulated occipital atrophy and reduced parietal clustering coefficient, while PD-non-converters showed fronto-parietal and temporal atrophy and increased sensorimotor path length. Both structural and functional baseline MRI alterations correlated with worse executive/attentive functions over time in PD-FoG. Higher parietal clustering coefficient at baseline differentiated PD-FoG–converters from PD-non-converters.

Conclusions:

Structural MRI is a useful tool to monitor PD progression, while functional MRI may be helpful to identify FoG conversion early.

Funding. Ministry of Education, Science, and Technological Development of the Republic of Serbia (#175090).

Background and Aims:

Parkinson’s disease (PD) patients are classified as tremor-dominant (TD) and postural instability and gait disorder (PIGD) phenotypes. The aim of this study was to investigate functional alterations within motor circuits of the cerebro-cerebellar system in PD-TD and PD-PIGD groups using stepwise functional connectivity (SFC) method.

Methods:

32 PD-TD and 26 PD-PIGD patients performed clinical/cognitive evaluations and resting-state functional MRI (fMRI). 60 age- and sex-matched controls were also enrolled. SFC analysis aims to characterize regions that connect to specific seed brain areas at different levels of link-step distances. The cerebellar seed-region was identified using motor task in 23 controls. For each of the SFC maps, two-sample t-test comparisons between groups were performed.

Results:

The performance of the fMRI-motor task was associated with activation of the lobule VI and vermis of the cerebellum. SFC analysis at one-link step distance showed, in both PD subtypes, a decreased connectivity between seed-region and thalamus and parietal lobe relative to controls; across intermediate link-steps, a reduced connectivity was observed with frontal, parietal and occipital lobes. Only PD-PIGD patients showed lower connectivity at intermediate link-step distances between the seed-cerebellar region and sensorimotor areas. Moreover, SFC pattern identified different localization of functional over‐connectivity in frontal lobe in both PD groups: inferior frontal gyrus and insula in PD-PIGD, and in orbitofrontal gyrus in PD-TD.

Conclusions:

These findings highlight subtype-specific PD changes in cerebellar functional connectivity, providing novel insights into the pathophysiological mechanism underlying different motor phenotypes.

Funding: Ministry of Education and Science Republic of Serbia (#175090), Italian Ministry of Health (#RF-2018-12366746).

Background and Aims:

To define post-acute cognitive and behavioural features in a large cohort of subjects with confirmed COVID-19.

Methods:

49 subjects with confirmed COVID-19 underwent a comprehensive neuropsychological assessment and a brain MRI scan within two months from hospital discharge. Frequencies of cognitive and behavioural alterations, according to the normative data, were reported. Total brain volumes were obtained. In all patients, correlations were performed between neuropsychological performances, brain volumes and the severity of acute-phase respiratory symptoms at the time of hospital admission.

Results:

At the time of the visit, 16% of patients presented with depressive symptoms and 18% reported post-traumatic stress disorder. 45% of the total sample showed executive dysfunctions, 30% visuospatial difficulties, and 25% long-term verbal and nonverbal memory problems. The youngest patients (age<50) showed the most severe profile with 75% of patients showing executive dysfunctions, 50% pure visuospatial dysfunctions and 40% primary long-term memory problems. The total sample showed a negative relationship between frontal executive performances and the severity of acute-phase respiratory symptoms at the hospital admission (R=-0.347; p<0.01). No significant relationship was observed between cognitive performances and brain volume.

Conclusions:

Cognitive and behavioural alterations are associated with COVID-19 infection within two months from hospital discharge and were more severe in the youngest patients. The patient cognitive/behavioural disturbances were independent of their brain structural integrity.

Further studies are needed to determine whether these alterations are directly linked with the infection itself or with its related consequences, and whether they are reversible or part of a neurodegenerative process.

Background and Aims:

Given the evidence of long-term neurological complications following COVID-19, including cognitive impairment¹, we aimed at assessing EEG cortical source densities (CSD) and linear lagged connectivity (LLC) values and their clinical, structural brain MRI and neuropsychological correlates in patients with recent COVID-19.

Methods:

We enrolled 49 adult patients with recent COVID-19, good recovery and cognitive disturbances, observed at 2-months post-discharge evaluation. Same-day 19-channel EEG and neuropsychological testing battery were performed; 36/49 patients underwent also 3T MRI. Thirty-three retrospective, age-/sex-matched healthy controls were selected, having no history of neurological or cognitive disturbances. Using low-resolution brain electromagnetic tomography (eLORETA) solutions at fixed frequencies², EEG lobar CSD and LLC values of COVID-19 and healthy subjects were investigated. Correlations with cognitive scores, recent and past medical history and white matter hyperintensities (WMH) volume were explored.

Results:

Patients showed pathological scores in memory, executive and visuo-spatial functions. 14/49 patients had symptoms suggestive of reactive depression. Analysis at delta frequency band (1.5-4.0 Hz) revealed higher CSD within bilateral frontal-temporal regions and greater LLC values between right frontal lobe and bilateral temporal and parietal-occipital lobes in COVID-19 patients. Delta CSD and LLC values positively correlated with executive performances, whereas no significant correlations were found with WMH, past and recent medical history.

Conclusions:

Differently from our acute-phase study³, EEG alterations after COVID-19 might be at least partially independent of acute infection severity and suggest instead a link with ongoing neuro-psychiatric symptoms. 8-months follow-up data will confirm the reversibility and/or evolution of our findings.

Background and Aims:

To investigate the relationship between emotion processing and resting state-functional connectivty (RS-FC) in healthy controls and in patients with frontotemporal lobar degeneration (FTLD).

Methods:

We recruited 80 FTLD (26 bvFTD, 10 PSP, 12 PPA, and 32 ALS) and 65 healthy controls. Participants underwent a RS-functional MRI (RS-fMRI) and the Comprehensive Affect Testing System. In each group, correlation models were performed between each emotion construct and RS-FC changes.

Results:

A high performance at the emotion naming was related in healthy controls with decreased RS-FC of the right inferior temporal gyrus within the right frontoparietal-network; and in FTLD patients with increased RS-FC of the frontal regions within salience, frontoparietal and executive-control networks. Furthermore, a high performance at the emotion differentiation was related in healthy controls with decreased RS-FC of the right middle temporal gyrus within the salience-network; and in FTLD patients with increased RS-FC of the left inferior and medial-orbitofrontal gyri, and right thalamus within the subcortical-network. Finally, a high performance at the emotion matching was related in both healthy controls and FTLD groups with increased RS-FC of precuneus and vermis within the visual-network, and with further increased RS-FC of bilateral lingual, middle temporal and calcarine gyri in FTLD group only.

Conclusions:

In FTLD compared to healthy controls, RS-FC associated with emotional performance involves a larger number of brain regions, which are linked to the disease development and progression. These findings offer new potential markers for detecting functional vulnerability linked to social interactions.

Funding: Italian Ministry of Health (GR-2013-02357415); European Research Council (StG-2016_714388_NeuroTRACK).

Background and Aims:

To apply mathematical modeling to unravel MRI connectomic signatures among the amyotrophic lateral sclerosis (ALS)-behavioral variant of frontotemporal dementia (bvFTD) spectrum.

Methods:

83 ALS, 35 bvFTD and 61 controls underwent clinical, cognitive evaluations and MRI scan. ALS were divided in 54 ALS with only motor deficits (ALS-cn), 21 ALS cognitively/behaviorally impaired (ALS-ci/bi) and 8 ALS with bvFTD (ALS-FTD).

Mathematical models based on connectomic approach and ROC curve analysis identified the characteristic patterns of damage of ALS-cn and bvFTD. Single-subject analysis was performed on ALS-ci/bi and ALS-FTD to assess shared features with ALS-cn and bvFTD.

Results:

The structural/functional patterns of damage characterizing ALS-cn and bvFTD were identified. ALS-like pattern resulted in a focused structural damage within motor areas. bvFTD-like pattern resulted in widespread structural damage and decreased functional connectivity, mainly in frontotemporoparietal areas. ALS-ci/bi showed structural damage mostly overlapping with the ALS-like pattern, whereas they diverged from ALS-cn in functional connectivity showing enhanced functional connectivity within sensorimotor and decreased functional connectivity in frontotemporal areas. The latter mirrored the bvFTD-like pattern. ALS-FTD patients resembled the bvFTD-like pattern of damage both structurally and functionally, with a frank structural ALS-like damage in motor areas.

Conclusions:

Alterations of the frontotemporoparietal network characterized bvFTD-like pattern, while a focal damage within sensorimotor-basal ganglia areas defined the ALS-like pattern. Commonalities and differences relative to the two ends of ALS-FTD spectrum were found in ALS-ci/bi and ALS-FTD.

Funding: The Italian Ministry of Health (GR-2011-02351217; GR-2013-02357415; RF-2011-02351193), AriSLA (ConnectALS), European Research Council (StG2016_714388_NeuroTRACK).

Abstract Body

Alzheimer’s disease (AD) is not a unitary clinical syndrome. Patients with early age-of-onset AD can present with multi-domain cognitive impairment at onset. This cognitive picture is very different from the typical profile of late-onset patients with progressive memory deficit as the central feature. AD can also present as atypical, relatively focal clinical syndromes, more frequently associated with early age-of-onset, i.e., as posterior cortical atrophy (PCA) and logopenic variant of primary progressive aphasia (lvPPA). Neuroimaging, including magnetic resonance imaging (MRI) and positron emission tomography (PET), is playing an increasingly important role in the study of atypical forms of AD, delineating the structural and functional brain alterations associated with these conditions. Neuroimaging patterns acquired at the prodromal stage can discriminate between AD and other neurodegenerative diseases and among AD variants. Advanced MRI techniques are of special interest for their potential to characterize the signature of each neurodegenerative condition and aid both the diagnostic process and the monitoring of disease progression. All these findings will become crucial when disease-modifying (personalized) therapies will be established.

Abstract Body

Alzheimer’s disease (AD) is not a unitary clinical syndrome. Patients with early age-of-onset AD can present with multi-domain cognitive impairment at onset. This cognitive picture is very different from the typical profile of late-onset patients with progressive memory deficit as the central feature. AD can also present as atypical, relatively focal clinical syndromes, more frequently associated with early age-of-onset, i.e., as posterior cortical atrophy (PCA) and logopenic variant of primary progressive aphasia (lvPPA). Neuroimaging, including magnetic resonance imaging (MRI) and positron emission tomography (PET), is playing an increasingly important role in the study of atypical forms of AD, delineating the structural and functional brain alterations associated with these conditions. Neuroimaging patterns acquired at the prodromal stage can discriminate between AD and other neurodegenerative diseases and among AD variants. Advanced MRI techniques are of special interest for their potential to characterize the signature of each neurodegenerative condition and aid both the diagnostic process and the monitoring of disease progression. All these findings will become crucial when disease-modifying (personalized) therapies will be established.