Publications by authors named "Camillo Marra"

104 Publications

Semantic Memory as an Early Cognitive Marker of Alzheimer's Disease: Role of Category and Phonological Verbal Fluency Tasks.

J Alzheimers Dis 2021 Apr 2. Epub 2021 Apr 2.

Neurology Unit, Department of Science of Elderly, Neuroscience, Head and Neck and Orthopaedics, Fondazione Policlinico A. Gemelli, IRCCS, Rome, Italy.

Background: The assessment of semantic memory may be a useful marker to identify individuals with mild cognitive impairment (MCI) who will progress to Alzheimer's disease (AD) in the early stages of the disease.

Objective: The aim of this five-year follow-up longitudinal study is to assess whether semantic assessment could predict progression in MCI.

Methods: A population of MCI (N = 251); mild (N = 178) and moderate AD (N = 114); and a sample of healthy participants (HP; N = 262) was investigated. The five-year follow-up of the MCI group was completed by 178 patients. Semantic and episodic memory measures were used, including a measure of the discrepancy between categorical and phonological verbal fluency, the semantic-phonological delta (SPD). The main outcome was the progression of MCI due to AD to dementia.

Results: A general linear model showed a significant effect of diagnosis on SPD (Wilks' Lambda = 0.591; p <  0.001). The estimated marginal means were -0.91 (SE = 0.185) in HP, -1.83 (SE = 0.187) in MCI, -1.16 (SE = 0.218) in mild AD, and -1.02 (SE = 0.275) in moderate AD. Post-hoc comparisons showed a significant difference between MCI and HP (p <  0.001). The follow-up was completed by 178 MCI individuals. SPD in MCI patients who progress to dementia was significantly lower than in MCI that will not progress (p = 0.003). Together with the Mini-Mental State Examination, the SPD was the only measure with a significant predicting effect at the five-years follow-up (p = 0.016).

Conclusion: The SPD indicate the impairment of semantic memory in individuals with underlying AD at the MCI early stage, reflecting the early involvement of perirhinal and entorhinal cortices in the earliest stages of AD neuropathological process.
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http://dx.doi.org/10.3233/JAD-201452DOI Listing
April 2021

The Impact of COVID-19 Quarantine on Patients With Dementia and Family Caregivers: A Nation-Wide Survey.

Front Aging Neurosci 2020 18;12:625781. Epub 2021 Jan 18.

Department of Medicine and Surgery and Milan Center for Neuroscience (NeuroMi), University of Milano-Bicocca, Monza, Italy.

Introduction: Previous studies showed that quarantine for pandemic diseases is associated with several psychological and medical effects. The consequences of quarantine for COVID-19 pandemic in patients with dementia are unknown. We investigated the clinical changes in patients with Alzheimer's disease and other dementias, and evaluated caregivers' distress during COVID-19 quarantine.

Methods: The study involved 87 Italian Dementia Centers. Patients with Alzheimer's Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia (FTD), and Vascular Dementia (VD) were eligible for the study. Family caregivers of patients with dementia were interviewed by phone in April 2020, 45 days after quarantine declaration. Main outcomes were patients' changes in cognitive, behavioral, and motor symptoms. Secondary outcomes were effects on caregivers' psychological features.

Results: 4913 patients (2934 females, 1979 males) fulfilled the inclusion criteria. Caregivers reported a worsening in cognitive functions in 55.1% of patients, mainly in subjects with DLB and AD. Aggravation of behavioral symptoms was observed in 51.9% of patients. In logistic regression analysis, previous physical independence was associated with both cognitive and behavioral worsening (odds ratio 1.85 [95% CI 1.42-2.39], 1.84 [95% CI 1.43-2.38], respectively). On the contrary, pandemic awareness was a protective factor for the worsening of cognitive and behavioral symptoms (odds ratio 0.74 [95% CI 0.65-0.85]; and 0.72 [95% CI 0.63-0.82], respectively). Approximately 25.9% of patients showed the onset of new behavioral symptoms. A worsening in motor function was reported by 36.7% of patients. Finally, caregivers reported a high increase in anxiety, depression, and distress.

Conclusion: Our study shows that quarantine for COVID-19 is associated with an acute worsening of clinical symptoms in patients with dementia as well as increase of caregivers' burden. Our findings emphasize the importance to implement new strategies to mitigate the effects of quarantine in patients with dementia.
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http://dx.doi.org/10.3389/fnagi.2020.625781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849158PMC
January 2021

Classification accuracy of TMS for the diagnosis of mild cognitive impairment.

Brain Stimul 2021 Mar-Apr;14(2):241-249. Epub 2021 Jan 13.

Neurology Unit, Department of Clinial and Experimental Sciences, University of Brescia, Italy. Electronic address:

Objective: To evaluate the performance of a Random Forest (RF) classifier on Transcranial Magnetic Stimulation (TMS) measures in patients with Mild Cognitive Impairment (MCI).

Methods: We applied a RF classifier on TMS measures obtained from a multicenter cohort of patients with MCI, including MCI-Alzheimer's Disease (MCI-AD), MCI-frontotemporal dementia (MCI-FTD), MCI-dementia with Lewy bodies (MCI-DLB), and healthy controls (HC). All patients underwent TMS assessment at recruitment (index test), with application of reference clinical criteria, to predict different neurodegenerative disorders. The primary outcome measures were the classification accuracy, precision, recall and F1-score of TMS in differentiating each disorder.

Results: 160 participants were included, namely 64 patients diagnosed as MCI-AD, 28 as MCI-FTD, 14 as MCI-DLB, and 47 as healthy controls (HC). A series of 3 binary classifiers was employed, and the prediction model exhibited high classification accuracy (ranging from 0.72 to 0.86), high precision (0.72-0.90), high recall (0.75-0.98), and high F1-scores (0.78-0.92), in differentiating each neurodegenerative disorder. By computing a new classifier, trained and validated on the current cohort of MCI patients, classification indices showed even higher accuracy (ranging from 0.83 to 0.93), precision (0.87-0.89), recall (0.83-1.00), and F1-scores (0.85-0.94).

Conclusions: TMS may be considered a useful additional screening tool to be used in clinical practice in the prodromal stages of neurodegenerative dementias.
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http://dx.doi.org/10.1016/j.brs.2021.01.004DOI Listing
January 2021

The Destiny of Multiple Domain Amnesic Mild Cognitive Impairment: Effect of Alternative Neuropsychological Definitions and Their Adjunctive Role in Respect of Memory Impairment.

Arch Clin Neuropsychol 2020 Dec 14. Epub 2020 Dec 14.

Departement of Neuroscience, Università Cattolica del Sacro Cuore, Roma, Italy.

Objective: Mild cognitive impairment is the main risk factor of dementia. Previous evidence has claimed that subjects with memory disturbances associated with impairment of other cognitive domains (multiple domain amnesic MCI) are at the highest risk of developing dementia. To date, a shared definition of amnesic MCI multiple domain (aMCI-MD) is still lacking.

Method: 163 subjects with aMCI were enrolled and followed-up for 2 years. They underwent a baseline comprehensive neuropsychological battery. The cut-off point for each test was set at 1, 1.5, and 2 SD below the mean obtained in normative studies; aMCI-MD was defined as the occurrence of abnormal scores on at least one, two, or three tests not assessing memory. The Episodic Memory Score (EMS), that measures the severity of memory impairment, was determined. Logistic regressionand Cox's proportional hazard risk models were carried out. The adjunctive effect of the definitions of aMCI-MD on the severity of memory impairment was assessed.

Results: Fifty-four subjects progressed to dementia. Only restrictive definitions of aMCI-MD (at least three tests below 1.5 SD; at least two tests below 2 SD) predicted conversion to dementia in both logistic regression and survival analysis. None of the conditions showed a significant adjunctive effect on the EMS.

Conclusions: The predictive effect of impairment in tests assessing cognitive domains other than memory depends on its psychometric definition. The use of a restrictive definition would be of some usefulness, but the adjunctive effect of such a definition on an integrated analysis of memory impairment may be questionable.
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http://dx.doi.org/10.1093/arclin/acaa094DOI Listing
December 2020

Accuracy and reproducibility of automated white matter hyperintensities segmentation with lesion segmentation tool: A European multi-site 3T study.

Magn Reson Imaging 2021 02 19;76:108-115. Epub 2020 Nov 19.

Laboratory of Alzheimer's Neuroimaging and Alzheimer's Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility of two freely available segmentation algorithms. A harmonized MRI protocol was implemented in 3T-scanners across 13 European sites, each scanning five volunteers twice (test-retest) using 2D-FLAIR. Automated segmentation was performed using Lesion segmentation tool algorithms (LST): the Lesion growth algorithm (LGA) in SPM8 and 12 and the Lesion prediction algorithm (LPA). To assess reproducibility, we applied the LST longitudinal pipeline to the LGA and LPA outputs for both the test and retest scans. We evaluated volumetric and spatial accuracy comparing LGA and LPA with manual tracing, and for reproducibility the test versus retest. Median volume difference between automated WMH and manual segmentations (mL) was -0.22[IQR = 0.50] for LGA-SPM8, -0.12[0.57] for LGA-SPM12, -0.09[0.53] for LPA, while the spatial accuracy (Dice Coefficient) was 0.29[0.31], 0.33[0.26] and 0.41[0.23], respectively. The reproducibility analysis showed a median reproducibility error of 20%[IQR = 41] for LGA-SPM8, 14% [31] for LGA-SPM12 and 10% [27] with the LPA cross-sectional pipeline. Applying the LST longitudinal pipeline, the reproducibility errors were considerably reduced (LGA: 0%[IQR = 0], p < 0.001; LPA: 0% [3], p < 0.001) compared to those derived using the cross-sectional algorithms. The DC using the longitudinal pipeline was excellent (median = 1) for LGA [IQR = 0] and LPA [0.02]. LST algorithms showed moderate accuracy and good reproducibility. Therefore, it can be used as a reliable cross-sectional and longitudinal tool in multi-site studies.
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http://dx.doi.org/10.1016/j.mri.2020.11.008DOI Listing
February 2021

Behavioral and Psychological Effects of Coronavirus Disease-19 Quarantine in Patients With Dementia.

Front Psychiatry 2020 9;11:578015. Epub 2020 Sep 9.

Regional Neurogenetic Centre, Department of Primary Care, ASP-CZ, Catanzaro, Italy.

Background: In March 2020, the World Health Organization declared a global pandemic due to the novel coronavirus SARS-CoV-2 and several governments planned a national quarantine in order to control the virus spread. Acute psychological effects of quarantine in frail elderly subjects with special needs, such as patients with dementia, have been poorly investigated. The aim of this study was to assess modifications of neuropsychiatric symptoms during quarantine in patients with dementia and their caregivers.

Methods: This is a sub-study of a multicenter nation-wide survey. A structured telephone interview was delivered to family caregivers of patients with diagnosis of Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VD), followed regularly at 87 Italian memory clinics. Variations in behavioral and psychological symptoms (BPSD) were collected after 1 month since quarantine declaration and associations with disease type, severity, gender, and caregiver's stress burden were analyzed.

Results: A total of 4,913 caregivers participated in the survey. Increased BPSD was reported in 59.6% of patients as worsening of preexisting symptoms (51.9%) or as new onset (26%), and requested drug modifications in 27.6% of these cases. Irritability, apathy, agitation, and anxiety were the most frequently reported worsening symptoms and sleep disorder and irritability the most frequent new symptoms. Profile of BPSD varied according to dementia type, disease severity, and patients' gender. Anxiety and depression were associated with a diagnosis of AD (OR 1.35, CI: 1.12-1.62), mild to moderate disease severity and female gender. DLB was significantly associated with a higher risk of worsening hallucinations (OR 5.29, CI 3.66-7.64) and sleep disorder (OR 1.69, CI 1.25-2.29), FTD with wandering (OR 1.62, CI 1.12-2.35), and change of appetite (OR 1.52, CI 1.03-2.25). Stress-related symptoms were experienced by two-thirds of caregivers and were associated with increased patients' neuropsychiatric burden (p<0.0001).

Conclusion: Quarantine induces a rapid increase of BPSD in approximately 60% of patients and stress-related symptoms in two-thirds of caregivers. Health services need to plan a post-pandemic strategy in order to address these emerging needs.
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http://dx.doi.org/10.3389/fpsyt.2020.578015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509598PMC
September 2020

Corticomotor Plasticity Predicts Clinical Efficacy of Combined Neuromodulation and Cognitive Training in Alzheimer's Disease.

Front Aging Neurosci 2020 8;12:200. Epub 2020 Jul 8.

Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, Boston, MA, United States.

Objective: To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training for treatment of cognitive symptoms in patients with Alzheimer's disease (AD). A secondary objective was to analyze associations between brain plasticity and cognitive effects of treatment.

Methods: In this randomized, sham-controlled, multicenter clinical trial, 34 patients with AD were assigned to three experimental groups receiving 30 daily sessions of combinatory intervention. Participants in the real/real group ( = 16) received 10 Hz repetitive transcranial magnetic stimulation (rTMS) delivered separately to each of six cortical regions, interleaved with computerized cognitive training. Participants in the sham rTMS group ( = 18) received sham rTMS combined with either real (sham/real group, = 10) or sham (sham/sham group, = 8) cognitive training. Effects of treatment on neuropsychological (primary outcome) and neurophysiological function were compared between the 3 treatment groups. These, as well as imaging measures of brain atrophy, were compared at baseline to 14 healthy controls (HC).

Results: At baseline, patients with AD had worse cognition, cerebral atrophy, and TMS measures of cortico-motor reactivity, excitability, and plasticity than HC. The real/real group showed significant cognitive improvement compared to the sham/sham, but not the real/sham group. TMS-induced plasticity at baseline was predictive of post-intervention changes in cognition, and was modified across treatment, in association with changes of cognition.

Interpretation: Combined rTMS and cognitive training may improve the cognitive status of AD patients, with TMS-induced cortical plasticity at baseline serving as predictor of therapeutic outcome for this intervention, and potential mechanism of action.

Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01504958.
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http://dx.doi.org/10.3389/fnagi.2020.00200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360860PMC
July 2020

Behavioral psychological symptoms of dementia and functional connectivity changes: a network-based study.

Neurobiol Aging 2020 10 16;94:196-206. Epub 2020 Jun 16.

Department of Neuroscience, Brighton & Sussex Medical School, University of Sussex, Brithon, UK; Department of Neuroscience "Rita Levi Montalcini", University of Torino, Turin, Italy.

Behavioral and psychological symptoms of dementia (BPSD) are commonly observed since the early stage of Alzheimer's disease (AD) associated with structural brain changes. It is conceivable that they may also relate to functional brain changes. This resting-state functional MRI (RS-fMRI) study investigated the alterations within functional brain networks of a cohort of AD patients at different clinical stages who presented with BPSD. One hundred one AD patients and 56 patients with amnestic mild cognitive impairment underwent a neuropsychological evaluation including the Neuropsychiatry Inventory-12 (NPI-12). All patients and 35 healthy controls (HS) underwent 3T-MRI. Factor analysis was used to extract the principal factors from NPI-12, while RS-fMRI data were processed using graph theory to investigate functional connectivity. Five factors were extracted from NPI-12. Sixty-two percent of patients showed BPSD and functional brain connectivity changes in various networks compared to those without BPSD and HS. These changes contributed to account for patients' BPSD. This work opens new perspectives in terms of nonpharmacological interventions that might be designed to modulate brain connectivity and improve patients' BPSD.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.06.009DOI Listing
October 2020

Semantic Priming in Mild Cognitive Impairment and Healthy Subjects: Effect of Different Time of Presentation of Word-Pairs.

J Pers Med 2020 Jun 29;10(3). Epub 2020 Jun 29.

Department of Neuroscience, Catholic University of Sacred Heart, 00168 Rome, Italy.

Introduction: Semantic memory is impaired in mild cognitive impairment (MCI). Twomain hypotheses about this finding are debated and refer to the degradation of stored knowledgeversus the impairment of semantic access mechanisms. The aim of our study is to evaluate semanticimpairment in MCI versus healthy subjects (HS) by an experiment evaluating semantic priming.

Methods: We enrolled 27 MCI and 20 HS. MCI group were divided, according to follow up, intoconverters-MCI and non converters-MCI. The semantic task consisted of 108 pairs of words, 54 ofwhich were semantically associated. Stimuli were presented 250 or 900 ms later the appearance ofthe target in a randomized manner. Data were analyzed using factorial ANOVA.

Results: Both HSand MCI answered more quickly for word than for non-word at both stimulus onset asynchrony(SOA) intervals. At 250 ms, both MCI and HS experienced a shorter time of response for relatedwordthan for unrelated words (priming effect), while only the converters-MCI subgroup lost thepriming effect. Further, we observed a rather larger Cohen's d effect size in non converters-MCIthan in converters-MCI.

Conclusion: Our data, and in particular the absence of a semantic primingeffect in converters-MCI, could reflect the impairment of semantic knowledge rather than theaccessibility of semantic stores in MCI individuals that progress to dementia.
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http://dx.doi.org/10.3390/jpm10030057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564260PMC
June 2020

An Italian Neurology Outpatient Clinic Facing SARS-CoV-2 Pandemic: Data From 2,167 Patients.

Front Neurol 2020 29;11:564. Epub 2020 May 29.

Dipartimento Scienze dell'Invecchiamento, Neurologiche, Ortopediche e della Testa-Collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Neurological sequelae of SARS-CoV-2 infection have already been reported, but there is insufficient data about the impact of the pandemic on the management of the patients with chronic neurological diseases. We aim to analyze the effect of COVID-19 pandemic and social restriction rules on these fragile patients. Patients with chronic neurologic diseases routinely followed at the outpatient clinic of Gemelli University Hospital, Rome, were assessed for symptoms suggestive of SARS-CoV-2 infection in the pandemic period, consequences of social restrictions, and neurological disease features, concomitant medical conditions, current medical and disease-specific treatments. Data source: a dedicated telephone survey designed to encompass questions on COVID-19 symptoms and on pandemic effects in chronic neurologic conditions. Overall, 2,167 individuals were analyzed: 63 patients reported contact with COVID-19 positive cases, 41 performed the swab, and 2 symptomatic patients tested positive for COVID-19 (0.09%). One hundred fifty-eight individuals (7%) needed urgent neurological care, deferred due to the pandemic; 641 patients (30%) suspended hospital treatments, physiotherapy or other support interventions; 405 individuals (19%) reported a subjective worsening of neurological symptoms. In our population, the presence of neurological chronic diseases did not increase the prevalence of COVID-19 infection. Nevertheless, the burden of neurological disorders has been worsened by the lockdown.
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http://dx.doi.org/10.3389/fneur.2020.00564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273723PMC
May 2020

Amygdalar nuclei and hippocampal subfields on MRI: Test-retest reliability of automated volumetry across different MRI sites and vendors.

Neuroimage 2020 09 13;218:116932. Epub 2020 May 13.

Laboratory of Alzheimer's Neuroimaging and Epidemiology (LANE), IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults.

Methods: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session.

Results: Significant MRI site and vendor effects (p ​< ​.05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman's r correlations >0.43, p ​< ​1.39E-36). In particular, volumes larger than 200 ​mm (for amygdalar nuclei) and 300 ​mm (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε ​< ​5% and DICE ​> ​0.80).

Conclusion: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116932DOI Listing
September 2020

Prospective Evaluation of Cognitive Functions After Rehabilitation With Cochlear Implant or Hearing Aids: Preliminary Results of a Multicentric Study on Elderly Patients.

Am J Audiol 2019 Oct 16;28(3S):762-774. Epub 2019 Oct 16.

ENT Audiology and Phoniatrics Unit, University Hospital of Pisa, Italy.

Objective Recent literature has shown a growing interest in the relationship between presbycusis and cognitive decline, but significant evidence about the long-term benefit of rehabilitation on cognitive functions has not been reported yet. The aim of the study was to analyze audiological and neuropsychological performances in patients with cochlear implant (CI) or hearing aids (HAs) over time. Materials and Method Forty-four bilaterally deaf patients aged more than 60 years (25 with CI candidacy and 19 with HA candidacy) were enrolled. Patients were subjected to audiological evaluation, to a battery of neuropsychological tests (Mini-Mental State Examination [MMSE], Rey Auditory Verbal Learning Task [RAVLT], Rey-Osterreith Complex Figure Test, Digit/Corsi Span Forward and Backward, Multiple Features Target Cancellation, Trail-Making Test, Stroop Test, and Phonological and Semantic Word Fluency), and to a quality of life assessment (Short Form 36, Glasgow Benefit Inventory, Glasgow Health Status Inventory) at the baseline and after a long-term follow-up (6-12 months). Results Speech recognition scores in quiet and in noise were significantly improved even 6 months after auditory rehabilitation. Significant differences between pre- and post-rehabilitation scores were reported in physical and emotional impacts in life, general global health, vitality, and social activities. MMSE and RAVLT scores were significantly improved in both groups after 6 months of follow-up, suggesting a global involvement of memory domain. Mnesic performances remained unchanged between the first and second follow-up, but a further significant improvement in executive functions (Stroop Test) was detected in patients with CI reevaluated 12 months after implantation. A significant correlation of the RAVLT with signal-to-noise ratio at +10 dB speech-in-noise scores and the MMSE with signal-to-noise ratio at 0 dB speech-in-noise scores suggests the pivotal role of executive functions in recognition in noisy environment. Conclusions Our preliminary data confirm that hearing deprivation in aged patients represents a truly modifiable risk factor for cognitive decline, which can be positively faced by acoustic rehabilitation. The improvement of short- and long-term memory performances and the amelioration of executive and attentive functions suggest that hearing restoration with both HAs and CI may provide a recovery of superior cognitive domains probably through a reallocation of cortical resources altered by hearing deprivation.
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http://dx.doi.org/10.1044/2019_AJA-HEAL18-18-0176DOI Listing
October 2019

Subclinical epileptiform activity during sleep in Alzheimer's disease and mild cognitive impairment.

Clin Neurophysiol 2020 05 5;131(5):1011-1018. Epub 2020 Mar 5.

Area of Neuroscience, IRCCS San Raffaele-Pisana, Rome, Italy.

Objective: Recent findings suggested that subclinical epileptiform activity is prevalent during sleep in a significant proportion of Alzheimer's Disease (AD) patients.

The Aims Of Our Study Were: (A) comparing the frequency of subclinical epileptiform activity during the sleep in a sample diagnosed with 'probable' AD and Mild Cognitive Impairment (MCI) due to AD, and in healthy subjects; (B) evaluating epileptiform EEG activity as a function of different sleep stages within a well-controlled polysomnographic setting.

Methods: We prospectively enrolled 50 'probable' AD patients (73 ± 7.0 years) and 50 subjects with MCI due to AD (72 ± 6.7 years) without history of seizures, comparing them with 50 controls (69 ± 6.7 years). Patients underwent to a full-night video-PSG.

Results: Subclinical epileptiform activity was detected in 6.38% of 'probable' AD patients, 11.63% of MCI due to AD subjects and 4.54% of controls (p = 0.43). The comparisons between the three groups for the frequency of epileptiform activity did not reach statistically significant differences neither for total sleep nor for any sleep period considered.

Conclusions: Our study shows that, when controlling for sleep stages and the influence of psychoactive drugs, AD patients and MCI due to AD subjects do not exhibit a higher frequency of epileptiform discharges during sleep compared to healthy subjects.

Significance: Subclinical epileptiform activity during sleep does not discriminate 'probable' AD from MCI due to AD and healthy controls.
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http://dx.doi.org/10.1016/j.clinph.2020.02.015DOI Listing
May 2020

Naming famous people through face and voice: a normative study.

Neurol Sci 2020 Jul 21;41(7):1859-1864. Epub 2020 Feb 21.

Institute of Neurology, Fondazione Policlinico Universitario "Agostino Gemelli", Rome, Italy.

Objectives: Within the large topic of naming disorders, an important and separated chapter belongs to proper names. Defects of proper naming could be a selective linguistic problem. Sometimes, it includes names belonging to various kinds of semantically unique entities, but other times, it has been observed for famous people proper names only. According to Bruce and Young's model, different stages allow to recognize, identify, and name famous people from their faces and voices, subsuming different anatomical pathways, both in right temporal lobe, and their different efficiency in this task. The present study aimed to report the normative data concerning the naming of the same famous people from voice and face.

Subjects And Methods: One hundred fifty-three normal subjects underwent a test in which they were requested to name famous people from their face and from their voice. The stimuli belonged to the previously published Famous People Recognition Battery.

Results: The mean percentage score on naming from face was 84.42 ± 12.03% (range 55.26-100%) and the mean percentage score on naming from voice was 66.04 ± 16.81% (range 28.13-100%). The difference observed in performance by face and by voice resulted significant (t| = 15.973; p < 0.001). Regression analyses showed that the percentage score obtained on naming from faces was predicted by education, whereas naming from voice was predicted by education and gender.

Discussion: Naming from voice is more difficult than from face, confirming a different difficulty of the two tasks. Education showed high predicting value for faces and less for voices, whereas gender contributed to predict results only for voices.
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http://dx.doi.org/10.1007/s10072-020-04272-1DOI Listing
July 2020

Cerebellar dentate nucleus functional connectivity with cerebral cortex in Alzheimer's disease and memory: a seed-based approach.

Neurobiol Aging 2020 05 15;89:32-40. Epub 2020 Jan 15.

Neuroimaging Laboratory, Fondazione Santa Lucia-IRCCS, Rome, Italy; Clinical Imaging Sciences Center, Brighton and Sussex Medical School, Brighton, UK.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by specific patterns of gray and white matter damage and cognitive/behavioral manifestations. The cerebellum has also been implicated in the pathophysiology of AD. Because the cerebellum is known to have strong functional connectivity (FC) with associative cerebral cortex regions, it is possible to hypothesize that it is incorporated into intrinsic FC networks relevant to cognitive manifestation of AD. In the present study, the cerebellar dentate nucleus, the largest cerebellar nucleus and the major output channel to the cerebral cortex, was chosen as the region of interest to test potential cerebellocerebral FC alterations and correlations with patients' memory impairment in a group of patients with AD. Compared to controls, patients with AD showed an increase in FC between the dentate nucleus and regions of the lateral temporal lobe. This study demonstrates that lower memory performances in AD may be related to altered FC within specific cerebellocortical functional modules, thus suggesting the cerebellar contribution to AD pathophysiology and typical memory dysfunctions.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.10.026DOI Listing
May 2020

Cerebellar White Matter Disruption in Alzheimer's Disease Patients: A Diffusion Tensor Imaging Study.

J Alzheimers Dis 2020 ;74(2):615-624

Neuroimaging Laboratory, Fondazione Santa Lucia, IRCCS, Rome, Italy.

The cognitive role of the cerebellum has recently gained much attention, and its pivotal role in Alzheimer's disease (AD) has now been widely recognized. Diffusion tensor imaging (DTI) has been used to evaluate the disruption of the microstructural milieu in AD, and though several white matter (WM) tracts such as corpus callosum, inferior and superior longitudinal fasciculus, cingulum, fornix, and uncinate fasciculus have been evaluated in AD, data on cerebellar WM tracts are currently lacking. We performed a tractography-based DTI reconstruction of the middle cerebellar peduncle (MCP), and the left and right superior cerebellar peduncles separately (SCPL and SCPR) and addressed the differences in fractional anisotropy (FA), axial diffusivity (Dax), radial diffusivity (RD), and mean diffusivity (MD) in the three tracts between 50 patients with AD and 25 healthy subjects. We found that AD patients showed a lower FA and a higher RD compared to healthy subjects in MCP, SCPL, and SCPR. Moreover, higher MD was found in SCPR and SCPL and higher Dax in SCPL. This result is important as it challenges the traditional view that WM bundles in the cerebellum are unaffected in AD and might identify new targets for therapeutic interventions.
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http://dx.doi.org/10.3233/JAD-191125DOI Listing
January 2020

CSF cutoffs for MCI due to AD depend on APOEε4 carrier status.

Neurobiol Aging 2020 05 30;89:55-62. Epub 2019 Dec 30.

Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.

Amyloid and tau pathological accumulation should be considered for Alzheimer's disease (AD) definition and before subjects' enrollment in disease-modifying trials. Although age, APOEε4, and sex influence cerebrospinal fluid (CSF) biomarker levels, none of these variables are considered by current normality/abnormality cutoffs. Using baseline CSF data from 2 independent cohorts (PharmaCOG/European Alzheimer's Disease Neuroimaging Initiative and Alzheimer's Disease Neuroimaging Initiative), we investigated the effect of age, APOEε4 status, and sex on CSF Aβ42/P-tau distribution and cutoff extraction by applying mixture models with covariates. The Aβ42/P-tau distribution revealed the presence of 3 subgroups (AD-like, intermediate, control-like) and 2 cutoffs. The identification of the intermediate subgroup and of the higher cutoff was APOEε4 dependent in both cohorts. APOE-specific classification (higher cutoff for APOEε4+, lower cutoff for APOEε4-) showed higher diagnostic accuracy in identifying MCI due to AD compared to single Aβ42 and Aβ42/P-tau cutoffs. APOEε4 influences amyloid and tau CSF markers and AD progression in MCI patients supporting i) the use of APOE-specific cutoffs to identify MCI due to AD and ii) the utility of considering APOE genotype for early AD diagnosis.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.12.019DOI Listing
May 2020

Small World Index in Default Mode Network Predicts Progression from Mild Cognitive Impairment to Dementia.

Int J Neural Syst 2020 Feb 20;30(2):2050004. Epub 2020 Jan 20.

Area of Neuroscience, IRCCS San Raffaele Pisana, Rome, Italy.

Aim of this study was to explore the EEG functional connectivity in amnesic mild cognitive impairments (MCI) subjects with multidomain impairment in order to characterize the Default Mode Network (DMN) in converted MCI (cMCI), which converted to Alzheimer's disease (AD), compared to stable MCI (sMCI) subjects. A total of 59 MCI subjects were recruited and divided -after appropriate follow-up- into cMCI or sMCI. They were further divided in MCI with linguistic domain (LD) impairment and in MCI with executive domain (ED) impairment. Small World (SW) index was measured as index of balance between integration and segregation brain processes. SW, computed restricting to nodes of DMN regions for all frequency bands, evaluated how they differ between MCI subgroups assessed through clinical and neuropsychological four-years follow-up. In addition, SW evaluated how this pattern differs between MCI with LD and MCI with ED. Results showed that SW index significantly decreased in gamma band in cMCI compared to sMCI. In cMCI with LD impairment, the SW index significantly decreased in delta band, while in cMCI with ED impairment the SW index decreased in delta and gamma bands and increased in alpha1 band. We propose that the DMN functional alterations in cognitive impairment could reflect an abnormal flow of brain information processing during resting state possibly associated to a status of pre-dementia.
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http://dx.doi.org/10.1142/S0129065720500045DOI Listing
February 2020

Semantic Relations in a Categorical Verbal Fluency Test: An Exploratory Investigation in Mild Cognitive Impairment.

Front Psychol 2019 17;10:2797. Epub 2019 Dec 17.

Area of Neuroscience, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Categorical verbal fluency tests (CFT) are commonly used to assess the integrity of semantic memory in individuals with brain damage. Persons with Dementia of the Alzheimer's Type display a reduced output on CFT, and a similar pattern has been reported in persons with amnesic Mild Cognitive Impairment (aMCI). The aims of the present study were to assess whether the semantic relations between lexical entries produced on a categorical fluency test were different between healthy persons and those with aMCI, and whether this difference was more pronounced in individuals who converted to dementia during a 3-year follow-up period.

Methods: We recruited 34 individuals with aMCI and 29 matched healthy persons. During the follow-up period, 10 individuals converted to Dementia (aMCI-conv). Two measures assessing semantic relations between consecutively produced word pairs (Path length and Extended Gloss Overlap) were obtained from the Wordnet database.

Results: The number of word pairs analyzed among the healthy participants (HP) and persons with aMCI were 498 (birds: 262; pieces of furniture: 236) and 395 (birds: 174; pieces of furniture: 221), respectively. Path length was lower in aMCI-conv than in HP ( = 0.035), but no differences were found between stable aMCI and HP, and between aMCI-stable and aMCI-conv. The ANOVA for lexical entries belonging to the "birds" category showed a significant effect of group ( = 5.630; = 0.004); the analysis showed a significant difference between HP and aMCI-conv ( = 0.003). The "pieces of furniture" category was significantly affected by group ( = 4.107; = 0.017); the test showed significant differences between aMCI-conv and healthy individuals ( = 0.049), and between aMCI-conv and stable aMCI ( = 0.001).

Discussion: Individuals with aMCI who convert to dementia show a deterioration in the semantic relations between lexical entries, produced on a CFT. This phenomenon may be interpreted as a marker of a very early disruption of semantic memory.
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http://dx.doi.org/10.3389/fpsyg.2019.02797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927990PMC
December 2019

Testing for the Myth of Cognitive Reserve: Are the Static and Dynamic Cognitive Reserve Indexes a Representation of Different Reserve Warehouses?

J Alzheimers Dis 2019 ;72(1):111-126

Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.

Background: Cognitive reserve (CR) explains the individual resilience to neurodegeneration. Years of formal education express the static measure of reserve (sCR). A dynamic aspect of CR (dCR) has been recently proposed.

Objective: The aim of the study was to compare sCR and dCR indexes, respectively, to detect brain abnormalities in Alzheimer's disease (AD) patients.

Methods: 117 individuals [39 AD, 40 amnestic mild cognitive impairment (aMCI), 38 healthy subjects (HS)] underwent neuropsychological evaluation and a 3T-MRI. T1-weighted volumes were used for manual segmentation of the hippocampus and of the parahippocampal cortices. Years of formal education were used as an index of sCR. Partial Least Square analysis was used to decompose the variance of individual MMSE scores, considered as a dCR index. In aMCI and AD patients, the brain abnormalities have been assessed comparing individuals with high and low levels of sCR and dCR in turn. Moreover, we investigated the effect of the different CR indexes in mediating the relationship between changes in brain volumes and memory performances.

Results: sCR and dCR indexes classified differently individuals having high or low levels of CR. Smaller hippocampal and parahippocampal volumes in high dCR patients were found. The sCR and dCR indexes mediated significantly the relationship between brain abnormalities and memory in patients.

Conclusions: CR mediated the relationship between brain and memory dysfunctions. We hypothesized that sCR and dCR indexes are a representation of different warehouses of reserve not operating in parallel but forming a complex system, in which crystalized cognitive abilities and actual cognitive efficiency interact with brain atrophy impacting on memory.
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http://dx.doi.org/10.3233/JAD-190716DOI Listing
November 2020

Does Hearing Loss in the Elderly Individuals Conform to Impairment of Specific Cognitive Domains?

J Geriatr Psychiatry Neurol 2020 07 15;33(4):231-240. Epub 2019 Sep 15.

Institute of Otorhinolaryngology, Catholic University of Sacred Heart, Fondazione Policlinico Universitario "A Gemelli", IRCCS, Rome, Italy.

Background: It is well known that age-related hearing loss (ARHL) is strongly associated with dementia. Different hypotheses have been considered to explain this link, including sensorial deprivation, the reduction in cognitive reserve, and the presence of shared pathological pathways (microvascular damage of the brain).

Aims: We carried out a study of the audiological and neuropsychological characteristics of a sample of hearing impaired but cognitively healthy individuals (HIH). The aim of our study was to carefully outline the neuropsychological profile of the patients in order to verify whether hearing loss correlated with deficits in specific cognitive domains.

Results: Episodic memory is affected by the presence of hearing loss, while semantic competences, syntactic, and grammar skills seem not to be affected. Furthermore, some audiological features linked to the intelligibility of spoken words can predict the presence of executive dysfunction; the same does not apply to memory impairment.

Conclusion: In HIH, executive functions are widely employed in maintaining an acceptable level of comprehension of spoken language; consequently, other cognitive domains and instrumental abilities in HIH are not properly supported. Thus, it is arguable that programs of hearing rehabilitation for HIH could restore the allocation of attentional resources to the functioning of other cognitive domains.
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http://dx.doi.org/10.1177/0891988719874117DOI Listing
July 2020

Patterns of Cerebellar Gray Matter Atrophy Across Alzheimer's Disease Progression.

Front Cell Neurosci 2018 20;12:430. Epub 2018 Nov 20.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

The role of the cerebellum in cognitive function has been broadly investigated in the last decades from an anatomical, clinical, and functional point of view and new evidence points toward a significant contribution of the posterior lobes of the cerebellum in cognition in Alzheimer's disease (AD). In the present work we used SUIT-VBM (spatially unbiased infratentorial template, voxel-based morphometry) to perform an analysis of the pattern of cerebellar gray matter (GM) atrophy in amnestic mild cognitive impairment (a-MCI) and AD dementia patients compared to healthy subjects (HS), in order to follow the changes of non-motor features of cerebellar degeneration throughout disease progression. This template has been validated to guarantee a significant improvement in voxel-to-voxel alignment of the individual fissures and the deep cerebellar nuclei compared to Montreal Neurological Institute (MNI) whole-brain template. Our analysis shows a progression of cerebellar GM volume changes throughout a continuous spectrum from early to late clinical stages of AD. In particular vermis and paravermian areas of the anterior (I-V) and posterior (VI) lobes are involved since the a-MCI stage, with a later involvement of the hemispheric part of the posterior lobes (VI lobule) and Crus I in AD dementia patients only. These findings support the role of the cerebellum in higher-level functions, and whilst confirming previous data on the involvement of Crus I in AD dementia, provide new evidence of an involvement of the vermis in the early stages of the disease.
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http://dx.doi.org/10.3389/fncel.2018.00430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255820PMC
November 2018

Two-Year Longitudinal Monitoring of Amnestic Mild Cognitive Impairment Patients with Prodromal Alzheimer's Disease Using Topographical Biomarkers Derived from Functional Magnetic Resonance Imaging and Electroencephalographic Activity.

J Alzheimers Dis 2019 ;69(1):15-35

Lab Alzheimer's Neuroimaging & Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Auditory "oddball" event-related potentials (aoERPs), resting state functional magnetic resonance imaging (rsfMRI) connectivity, and electroencephalographic (rsEEG) rhythms were tested as longitudinal functional biomarkers of prodromal Alzheimer's disease (AD). Data were collected at baseline and four follow-ups at 6, 12, 18, and 24 months in amnesic mild cognitive impairment (aMCI) patients classified in two groups: "positive" (i.e., "prodromal AD"; n = 81) or "negative" (n = 63) based on a diagnostic marker of AD derived from cerebrospinal samples (Aβ42/P-tau ratio). A linear mixed model design was used to test functional biomarkers for Group, Time, and Group×Time effects adjusted by nuisance covariates (only data until conversion to dementia was used). Functional biomarkers that showed significant Group effects ("positive" versus "negative", p < 0.05) regardless of Time were 1) reduced rsfMRI connectivity in both the default mode network (DMN) and the posterior cingulate cortex (PCC), both also giving significant Time effects (connectivity decay regardless of Group); 2) increased rsEEG source activity at delta (<4 Hz) and theta (4-8 Hz) rhythms and decreased source activity at low-frequency alpha (8-10.5 Hz) rhythms; and 3) reduced parietal and posterior cingulate source activities of aoERPs. Time×Group effects showed differential functional biomarker progression between groups: 1) increased rsfMRI connectivity in the left parietal cortex of the DMN nodes, consistent with compensatory effects and 2) increased limbic source activity at theta rhythms. These findings represent the first longitudinal characterization of functional biomarkers of prodromal AD relative to "negative" aMCI patients based on 5 serial recording sessions over 2 years.
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http://dx.doi.org/10.3233/JAD-180158DOI Listing
September 2020

Learning Processes and Brain Connectivity in A Cognitive-Motor Task in Neurodegeneration: Evidence from EEG Network Analysis.

J Alzheimers Dis 2018 ;66(2):471-481

Università Cattolica del Sacro Cuore, Istituto di Neurologia, Roma, Italia.

Electroencephalographic (EEG) rhythms are linked to any kind of learning and cognitive performance including motor tasks. The brain is a complex network consisting of spatially distributed networks dedicated to different functions including cognitive domains where dynamic interactions of several brain areas play a pivotal role. Brain connectome could be a useful approach not only to mechanisms underlying brain cognitive functions, but also to those supporting different mental states. This goal was approached via a learning task providing the possibility to predict performance and learning along physiological and pathological brain aging. Eighty-six subjects (22 healthy, 47 amnesic mild cognitive impairment, 17 Alzheimer's disease) were recruited reflecting the whole spectrum of normal and abnormal brain connectivity scenarios. EEG recordings were performed at rest, with closed eyes, both before and after the task (Sensory Motor Learning task consisting of a visual rotation paradigm). Brain network properties were described by Small World index (SW), representing a combination of segregation and integration properties. Correlation analyses showed that alpha 2 SW in pre-task significantly predict learning (r  =  -0.2592, p < 0.0342): lower alpha 2 SW (higher possibility to increase during task and better the learning of this task), higher the learning as measured by the number of reached targets. These results suggest that, by means of an innovative analysis applied to a low-cost and widely available techniques (SW applied to EEG), the functional connectome approach as well as conventional biomarkers would be effective methods for monitoring learning progress during training both in normal and abnormal conditions.
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http://dx.doi.org/10.3233/JAD-180342DOI Listing
October 2019

In vivo mapping of brainstem nuclei functional connectivity disruption in Alzheimer's disease.

Neurobiol Aging 2018 12 23;72:72-82. Epub 2018 Aug 23.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Neuroscience, Brighton & Sussex Medical School, University of Sussex, Brighton, East Sussex, United Kingdom. Electronic address:

We assessed here functional connectivity changes in the locus coeruleus (LC) and ventral tegmental area (VTA) of patients with Alzheimer's disease (AD). We recruited 169 patients with either AD or amnestic mild cognitive impairment due to AD and 37 elderly controls who underwent cognitive and neuropsychiatric assessments and resting-state functional magnetic resonance imaging at 3T. Connectivity was assessed between LC and VTA and the rest of the brain. In amnestic mild cognitive impairment patients, VTA disconnection was predominant with parietal regions, while in AD patients, it involved the posterior nodes of the default-mode network. We also looked at the association between neuropsychiatric symptoms (assessed by the neuropsychiatric inventory) and VTA connectivity. Symptoms such as agitation, irritability, and disinhibition were associated with VTA connectivity with the parahippocampal gyrus and cerebellar vermis, while sleep and eating disorders were associated with VTA connectivity to the striatum and the insular cortex. This suggests a contribution of VTA degeneration to AD pathophysiology and to the occurrence of neuropsychiatric symptoms. We did not find evidence of LC disconnection, but this could be explained by the size of this nucleus, which makes it difficult to isolate. These results are consistent with animal findings and have potential implications for AD prognosis and therapies.
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http://dx.doi.org/10.1016/j.neurobiolaging.2018.08.012DOI Listing
December 2018

Sustainable method for Alzheimer dementia prediction in mild cognitive impairment: Electroencephalographic connectivity and graph theory combined with apolipoprotein E.

Ann Neurol 2018 08 25;84(2):302-314. Epub 2018 Aug 25.

Institute of Neurology, Area of Neuroscience, Catholic University of The Sacred Heart.

Objective: Mild cognitive impairment (MCI) is a condition intermediate between physiological brain aging and dementia. Amnesic-MCI (aMCI) subjects progress to dementia (typically to Alzheimer-Dementia = AD) at an annual rate which is 20 times higher than that of cognitively intact elderly. The present study aims to investigate whether EEG network Small World properties (SW) combined with Apo-E genotyping, could reliably discriminate aMCI subjects who will convert to AD after approximately a year.

Methods: 145 aMCI subjects were divided into two sub-groups and, according to the clinical follow-up, were classified as Converted to AD (C-MCI, 71) or Stable (S-MCI, 74).

Results: Results showed significant differences in SW in delta, alpha1, alpha2, beta2, gamma bands, with C-MCI in the baseline similar to AD. Receiver Operating Characteristic(ROC) curve, based on a first-order polynomial regression of SW, showed 57% sensitivity, 66% specificity and 61% accuracy(area under the curve: AUC=0.64). In 97 out of 145 MCI, Apo-E allele testing was also available. Combining this genetic risk factor with Small Word EEG, results showed: 96.7% sensitivity, 86% specificity and 91.7% accuracy(AUC=0.97). Moreover, using only the Small World values in these 97 subjects, the ROC showed an AUC of 0.63; the resulting classifier presented 50% sensitivity, 69% specificity and 59.6% accuracy. When different types of EEG analysis (power density spectrum) were tested, the accuracy levels were lower (68.86%).

Interpretation: Concluding, this innovative EEG analysis, in combination with a genetic test (both low-cost and widely available), could evaluate on an individual basis with great precision the risk of MCI progression. This evaluation could then be used to screen large populations and quickly identify aMCI in a prodromal stage of dementia. Ann Neurol 2018 Ann Neurol 2018;84:302-314.
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http://dx.doi.org/10.1002/ana.25289DOI Listing
August 2018

Diagnostic and prognostic role of semantic processing in preclinical Alzheimer's disease.

Biomark Med 2018 06 13;12(6):637-651. Epub 2018 Jun 13.

Institute of Neurology, Università Cattolica del Sacro Cuore, Rome; Memory Clinic, Fondazione Policlinico Universitario 'A Gemelli', Rome, Italy.

Relatively spared during most of the timeline of normal aging, semantic memory shows a subtle yet measurable decline even during the pre-clinical stage of Alzheimer's disease. This decline is thought to reflect early neurofibrillary changes and impairment is detectable using tests of language relying on lexical-semantic abilities. A promising approach is the characterization of semantic parameters such as typicality and age of acquisition of words, and propositional density from verbal output. Seminal research like the Nun Study or the analysis of the linguistic decline of famous writers and politicians later diagnosed with Alzheimer's disease supports the early diagnostic value of semantic processing and semantic memory. Moreover, measures of these skills may play an important role for the prognosis of patients with mild cognitive impairment.
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http://dx.doi.org/10.2217/bmm-2017-0324DOI Listing
June 2018

Quantitative Magnetization Transfer of White Matter Tracts Correlates with Diffusion Tensor Imaging Indices in Predicting the Conversion from Mild Cognitive Impairment to Alzheimer's Disease.

J Alzheimers Dis 2018 ;63(2):561-575

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome.

Patients with amnestic mild cognitive impairment (aMCI) have higher probability to develop Alzheimer's disease (AD) than elderly controls. The detection of subtle changes in brain structure associated with disease progression and the development of tools to identify patients at high risk for dementia in a short time is crucial. Here, we used probabilistic white matter (WM) tractography to explore microstructural alterations within the main association, limbic, and commissural pathways in aMCI patients who converted to AD after 1 year follow-up (MCIconverters) and those who remained stable (MCIstable). Both diffusion tensor imaging (DTI) and quantitative magnetization transfer (qMT) parameters have been considered for a comprehensive pathophysiological characterization of the WM damage. Overall, tract-specific parameters derived from qMT and DTI at baseline were able to differentiate aMCI patients who converted to AD from those who remained stable in time. In particular, the qMT exchange rate, RMB0, of the right uncinate fasciculus was significantly decreased in MCIconverters, whereas fractional anisotropy was significantly decreased in the bilateral superior cingulum in MCIconverters compared to MCIstable. These results confirm the involvement of WM and particularly of association fibers in the progression of AD, highlighting disconnection as a potential mechanism.
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http://dx.doi.org/10.3233/JAD-170995DOI Listing
June 2019

Famous people recognition through personal name: a normative study.

Neurol Sci 2018 Apr 30;39(4):663-669. Epub 2018 Jan 30.

Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy.

In this normative study, we investigated famous people recognition through personal name, using as stimuli the names of the same 40 Italian famous persons whose faces and voices had been utilized for the normative study of the Famous People Recognition Battery. For each famous people, we assessed name familiarity, person identification (when the name had been considered as familiar), and false alarms. The investigation was carried out on 143 normal subjects who varied in age and education. Name familiarity and semantic scores were affected by educational level, whereas age influenced false alarms. A comparison between results obtained with names in this research and with faces and voices of the same famous people in our previous study showed that familiarity scores were higher for personal names than those for faces and voices, which obtained the worst scores. Person identification scores were not significantly different from names and from faces, but both these scores were significantly higher than the semantic scores obtained by voices. Taken together, these results are inconsistent with the influential interactive activation and competition model of person recognition.
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http://dx.doi.org/10.1007/s10072-018-3251-3DOI Listing
April 2018

Whole brain white matter histogram analysis of diffusion tensor imaging data detects microstructural damage in mild cognitive impairment and alzheimer's disease patients.

J Magn Reson Imaging 2018 Jan 21. Epub 2018 Jan 21.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

Background: Amnestic mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease (AD). However, the clinical conversion from MCI to AD is unpredictable. Hence, identification of noninvasive biomarkers able to detect early changes induced by dementia is a pressing need.

Purpose: To explore the added value of histogram analysis applied to measures derived from diffusion tensor imaging (DTI) for detecting brain tissue differences between AD, MCI, and healthy subjects (HS).

Study Type: Prospective.

Population/subjects: A local cohort (57 AD, 28 MCI, 23 HS), and an Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (41 AD, 58 MCI, 41 HS).

Field Strength: 3T. Dual-echo turbo spin echo (TSE); fluid-attenuated inversion recovery (FLAIR); modified-driven-equilibrium-Fourier-transform (MDEFT); inversion-recovery spoiled gradient recalled (IR-SPGR); diffusion tensor imaging (DTI).

Assessment: Normal-appearing white matter (NAWM) masks were obtained using the T -weighted volumes for tissue segmentation and T -weighted images for removal of hyperintensities/lesions. From DTI images, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AXD), and radial diffusivity (RD) were obtained. NAWM histograms of FA, MD, AXD, and RD were derived and characterized estimating: peak height, peak location, mean value (MV), and quartiles (C25, C50, C75), which were compared between groups. Receiver operating characteristic (ROC) and area under ROC curves (AUC) were calculated. To confirm our results, the same analysis was repeated on the ADNI dataset.

Statistical Tests: One-way analysis of variance (ANOVA), post-hoc Student's t-test, multiclass ROC analysis.

Results: For the local cohort, C25 of AXD had the maximum capability of group discrimination with AUC of 0.80 for "HS vs. patients" comparison and 0.74 for "AD vs. others" comparison. For the ADNI cohort, MV of AXD revealed the maximum group discrimination capability with AUC of 0.75 for "HS vs. patients" comparison and 0.75 for "AD vs. others" comparison.

Data Conclusion: AXD of NAWM might be an early marker of microstructural brain tissue changes occurring during the AD course and might be useful for assessing disease progression.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.
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http://dx.doi.org/10.1002/jmri.25947DOI Listing
January 2018