Daniela Perani

San Raffaele Scientific Institute | OSR · Specialità in Medicina Nucleare e Centro Pet

Objectives: We investigated tau and neurodegeneration patterns and clinical phenotypes in carriers of a specific pathogenic variant in the PSEN1 gene and 1 nonaffected relative. Methods: We included 3 symptomatic carriers of the c.436 A>C, p.Met146Leu, NM_000021.4, rs63750306 variant in the PSEN1 gene, pathogenic for autosomal dominant Alzheimer...

Purpose: Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are essential molecular imaging tools for the in vivo investigation of neurotransmission. Traditionally, PET and SPECT images are analysed in a univariate manner, testing for changes in radiotracer binding in regions or voxels of interest independentl...

Methods This study assessed data from two cohorts of patients with alpha‐synucleinopathies (University of Brescia and University of Rome Tor‐Vergata cohorts). Consecutive participants with video‐polysomnography‐confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and ¹²³I‐FP‐CIT SPE...

We evaluated 128 GBA and 432 nonGBA Parkinson’s disease (PD) subjects. Baseline clinical features and dopaminergic activity were assessed, together with 7-year clinical follow-up. Survival analyses assessed the independent and interactive effects of male sex and GBA1 mutations on cognitive impairment. At baseline, GBA-PD males showed greater motor...

Purpose Our study examines brain metabolic connectivity in SARS-CoV-2 survivors during the acute-subacute and chronic phases, aiming to elucidate the mechanisms underlying the persistence of neurological symptoms in long-COVID patients. Methods We perfomed a cross-sectional study including 44 patients (pts) with neurological symptoms who underwent...

Currently available data show mixed results as to whether the processing of emotional information has the same characteristics in the native (L1) as in the second language (L2) of bilinguals. We conducted a functional magnetic resonance imaging (fMRI) experiment to shed light on the neurocognitive mechanisms underlying bilinguals’ emotional process...

Background In recent years, significant efforts have been directed towards the research and development of disease-modifying therapies for dementia. These drugs focus on prodromal (mild cognitive impairment, MCI) and/or early stages of Alzheimer’s disease (AD). Literature evidence indicates that a considerable proportion of individuals with MCI do...

Introduction Amyloid-β (Aβ) plaques is a significant hallmark of Alzheimer's disease (AD), detectable via amyloid-PET imaging. The Fluorine-18-Fluorodeoxyglucose ([¹⁸F]FDG) PET scan tracks cerebral glucose metabolism, correlated with synaptic dysfunction and disease progression and is complementary for AD diagnosis. Dual-scan acquisitions of amyloi...

Background and Objective: Heterozygous variants in the glucocerebrosidase gene (GBA1) are the major genetic risk factor for Parkinson's Disease (PD). GBA-PD has been associated with worse progression and higher risk of cognitive decline. Here we took advantage of the Parkinson's Progression Markers Initiative (PPMI) to investigate whether sex could...

Objectives Mild cognitive impairment presenting with an amnestic syndrome (aMCI) and amyloid positivity is considered due to AD. Many subjects, however, can show an overall very slow progression relevant for differential diagnosis, prognosis, and treatment. This study assessed PET biomarkers, including brain glucose metabolism, tau, and amyloid loa...

Subthalamic nucleus deep brain stimulation (STN-DBS) alleviates motor symptoms of Parkinson’s disease (PD), thereby improving quality of life. However, quantitative brain markers to evaluate DBS responses and select suitable patients for surgery are lacking. Here, we used metabolic brain imaging to identify a reproducible STN-DBS network for which...

A proportion of patients clinically diagnosed with Parkinson’s disease (PD) can have a 123I-FP-CIT-SPECT scan without evidence of dopaminergic deficit (SWEDD), generating a debate about the underlying biological mechanisms. This study investigated differences in clinical features, 123I-FP-CIT binding, molecular connectivity, as well as clinical and...

Background Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical co...

Both post-mortem and in vivo data argue for dopamine dysfunction in patients with Alzheimer’s Disease (AD). However, the timing and regional progression of dopaminergic systems alterations in AD are still debated. Aim of the study was to investigate in vivo the pattern of dopaminergic changes and connectivity using DAT-SPECT imaging in patients acr...

Background ¹⁸ F‐Flortaucipir‐PET allows visualization of tau deposits (T) representing a powerful diagnostic and prognostic tool for Alzheimer’s disease (AD). Dual‐phase ¹⁸ F‐Flortaucipir‐PET can also evaluate neurodegeneration (N) through the early‐phase images. We aim to assess the diagnostic and prognostic power of visual and semi‐quantitative T...

Background Picture naming tests are widely used to evaluate language impairments, especially in Primary Progressive Aphasia (PPA). The available instruments differ for type of stimuli and their psycholinguistic properties, known to affect the performance. We aim to identify the most appropriate naming test to be used on PPA, based on clinical and r...

Background In recent years, considerable efforts have been directed towards the research and development of disease-modifying therapies for dementia. These drugs focus on prodromal (Mild Cognitive Impairment, MCI) and/or early stages of Alzheimer's disease. Evidence from literature demonstrates that a considerable proportion of MCI subjects never p...

Introduction: Brain hypometabolism patterns have been previously associated with cognitive decline in Parkinson's disease (PD). Our aim is to evaluate the impact of single-subject fluorodeoxyglucose (FDG)-PET brain hypometabolism on long-term cognitive and motor outcomes in PD. Methods: Forty-nine non-demented PD patients with baseline brain FDG-P...

INTRODUCTION Tau and neurodegeneration strongly correlate with cognitive impairment, as compared to amyloid. However, their contribution in explaining cognition and predicting cognitive decline in memory clinics remains unclarified. METHODS We included 94 participants with Mini‐Mental State Examination (MMSE), tau positron emission tomography (PET...

INTRODUCTION Amnestic mild cognitive impairment (aMCI) is emerging as a heterogeneous condition. METHODS We looked at a cohort of N = 207 aMCI subjects, with baseline fluorodeoxyglucose positron emission tomography (FDG‐PET), T1 magnetic resonance imaging, cerebrospinal fluid (CSF), apolipoprotein E (APOE), and neuropsychological assessment. An al...

Background: Brain imaging with [18F]FDG-PET can support the diagnostic work-up of patients with α-synucleinopathies. Validated data analysis approaches are necessary to evaluate disease-specific brain metabolism patterns in neurodegenerative disorders. This study compared the univariate Statistical Parametric Mapping (SPM) single-subject procedure...

Background: Early- and late-onset dementia with Lewy bodies (EO-DLB and LO-DLB) are similar in terms of core symptoms. However, LO-DLB presents with more amnestic deficits, while EO-DLB shows a rapid cognitive decline and more severe neuropsychiatric symptoms at onset. A contribution of neurotransmitter dysfunction was suggested but never explored...

Background Alzheimer’s disease (AD) neuropathologic changes are β‐amyloid (Aβ) deposition, pathologic tau, and neurodegeneration. Dual‐phase amyloid‐PET might be able to evaluate Aβ deposition and neurodegeneration with a single tracer injection. Early‐frames of amyloid‐PET scans provide a proxy for cerebral perfusion, which has shown good correlat...

Purpose Isolated REM sleep behaviour disorder (iRBD) patients are at high risk of developing clinical syndromes of the α-synuclein spectrum. Progression markers are needed to determine the neurodegenerative changes and to predict their conversion. Brain imaging with ¹⁸F-FDG PET in iRBD is promising, but longitudinal studies are scarce. We investiga...

Picture naming tests are widely used to evaluate language impairments in neurodegenerative diseases, especially in Primary Progressive Aphasia (PPA). The available tests differ for many factors affecting the performance, e.g. format of stimuli and their psycholinguistic properties. We aim to identify the most appropriate naming test to be used on P...

Objectives: Attention-deficit hyperactivity disorder (ADHD) in adulthood shows high co-occurrence rates with cocaine use disorder (CoUD). The self-medication hypothesis (SMH) provides a theoretical explanation for this comorbidity. This study investigates the neurobiological mechanisms that could support SMH in adult patients with ADHD-CoUD. Mate...

Introduction: The impairment of nigrostriatal dopaminergic network is a core feature of dementia with Lewy bodies (DLB). The involvement and reconfiguration of extranigrostriatal dopaminergic circuitries in the DLB continuum is still theme of debate. We aim to investigate in vivo the dynamic changes of local and long-distance dopaminergic networks...

Purpose Dementia with Lewy bodies (DLB) is characterized by a wide clinical and biological heterogeneity, with sex differences reported in both clinical and pathologically confirmed DLB cohorts. No research evidence is available on sex differences regarding molecular neurotransmission. This study aimed to assess whether sex can influence neurotrans...

We investigated how sex modulates metabolic connectivity alterations in probable dementia with Lewy bodies (pDLB). We included 131 pDLB patients (males/females: 58/73) and similarly aged healthy controls (HC) (male/female: 59/75) with available (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans. We assessed (1) sex differences i...

In the past two decades brain connectomics has evolved into a major concept in neuroscience. However, the current perspective on brain connectivity and how it underpins brain function relies mainly on the hemodynamic signal of functional magnetic resonance imaging (MRI). Molecular imaging provides unique information inaccessible to MRI-based and el...

This scientific commentary refers to ‘Interrelation of striatal dopamine, brain metabolism and cognition in dementia with Lewy bodies’ by Yoo et al. (https://doi.org/10.1093/brain/awac084).

Objective This study investigates the effects of manual and semi-automatic methods for assessing MIBG semi-quantitative indices in a clinical setting. Materials and methods We included ¹²³ I-MIBG scans obtained in 35 patients with idiopathic Parkinson’s Disease. Early and late heart-to-mediastinum (H/M) ratios were calculated from ¹²³ I-MIBG image...

Introduction Timely detection of cognitive decline in primary care is essential to promote an appropriate care pathway and enhance the benefits of interventions. We present the results of a study aimed to evaluate the effectiveness of an educational intervention addressed to Italian family physicians (FPs) to improve timely detection and management...

Purpose: Dementia with Lewy bodies (DLB) is characterized by a wide clinical and biological heterogeneity, with sex differences reported in both clinical and pathologically confirmed DLB cohorts. No research evidence is available on sex differences regarding molecular neurotransmission. This study aimed to assess whether sex can influenceneurotrans...

Background and Objectives The ALS diagnosis requires an integrative approach, combining the clinical examination and supporting tests. Nevertheless, in several cases, the diagnosis proves to be suboptimal, and for this reason, new diagnostic methods and novel biomarkers are catching on. The ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)-PET could be a helpful me...

Primary progressive aphasia (PPA) classification relies on profile characterization of quantitatively impaired/spared performance in language tasks. In this study, we coextracted eight qualitative types of errors in 67 PPA patients submitted to a comprehensive language assessment. Canonical correlation analysis was applied to simultaneously correla...

PurposeWe evaluated brain metabolic dysfunctions and associations with neurological and biological parameters in acute, subacute and chronic COVID-19 phases to provide deeper insights into the pathophysiology of the disease.Methods Twenty-six patients with neurological symptoms (neuro-COVID-19) and [18F]FDG-PET were included. Seven patients were ac...

Previous evidence suggests that the derangement of large-scale brain networks reflects structural, molecular, and functional mechanisms underlying neurodegenerative diseases. Although the alterations of multiple large-scale brain networks in Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are reported, a comprehensive study on connecti...

Background and Objectives Amyloid-related imaging abnormalities suggestive of vasogenic edema or sulcal effusion (ARIA-E) are the most common adverse events complicating Alzheimer’s disease (AD) immunotherapy with anti-amyloid-beta (Aβ) monoclonal antibodies (mAbs). ARIA-E can also occur spontaneously in cerebral amyloid angiopathy-related inflamma...

Background: Alzheimer's disease (AD) neuropathologic changes are β-amyloid (Aβ) deposition, pathologic tau, and neurodegeneration. Dual-phase amyloid-PET might be able to evaluate Aβ deposition and neurodegeneration with a single tracer injection. Early-phase amyloid-PET scans provide a proxy for cerebral perfusion, which has shown good correlation...

Functional network-level alterations in the semantic variant of Primary Progressive Aphasia (sv-PPA) are relevant to understanding the clinical features and the neural spreading of the pathology. We assessed the effect of neurodegeneration on brain systems reorganization in early sv-PPA, using advanced brain metabolic connectivity approaches. Forty...

Background and objective: Multicenter study aiming at investigating the characteristics of cognitive decline, neuropsychiatric symptoms, and brain imaging in individuals with subjective cognitive decline (SCD) and subtle cognitive decline (pre-Mild Cognitive Impairment, pre-MCI). Methods: Data were obtained from the Network-AD project (NET-2011-...

Previous brain functional specialization evidence has shown that both aware and unaware visual processing of manipulable objects activate left premotor, parietal, and posterior temporal cortices, which are thought to constitute object-directed action and object-function processing streams. An open question is whether, both under supraliminal and su...

Introduction Dementia with Lewy bodies (DLB) may represent a diagnostic challenge, since its clinical picture overlaps with other dementia. Two toolkits have been developed to aid the clinician to diagnose DLB: the Lewy Body Composite Risk Score (LBCRS) and the Assessment Toolkit for DLB (AT-DLB). We aim to evaluate the reliability of these two que...

Epilepsy is classically considered a childhood disease. However, it represents the third most frequent neurological condition in the elderly, following stroke, and dementia. With the progressive aging of the general population, the number of patients with Late-Onset Epilepsy (LOE) is constantly growing, with important economic and social consequenc...

Deep learning (DL) strategies applied to magnetic resonance (MR) images in positron emission tomography (PET)/MR can provide synthetic attenuation correction (AC) maps, and consequently PET images, more accurate than segmentation or atlas-registration strategies. As first objective, we aim to investigate the best MR image to be used and the best po...

Computational morphometry of magnetic resonance images represents a powerful tool for studying macroscopic differences in human brains. In the present study (N participants = 829), we combined different techniques and measures of brain morphology to investigate one of the most compelling topics in neuroscience: sexual dimorphism in human brain stru...

Positron emission tomography (PET) with perfusion and metabolism tracers, the first functional brain imaging method extensively applied to the study of the brain correlates of human cognitive function, has played a central role in the study of aphasia due to stroke. By showing the extent of intra-hemispheric and interhemispheric remote effects asso...

Background Preclinical and pathology evidence suggests an involvement of brain dopamine (DA) circuitry in Alzheimer’s disease (AD). We in vivo investigated if, when, and in which target regions [123I]FP-CIT-SPECT regional binding and molecular connectivity are damaged along the AD course. Methods We retrospectively selected 16 amyloid-positive sub...

Lifelong bilingualism is associated with delayed dementia onset, suggesting a protective effect on the brain. Here, we aim to study the effects of lifelong bilingualism as a dichotomous and continuous phenomenon, on brain metabolism and connectivity in individuals with Alzheimer's dementia. Ninety-eight patients with Alzheimer's dementia (56 monoli...

Background and Aims: Many clinical trials on potentially disease-modifying drugs are focused to mild cognitive impairment (MCI) prodromal-to-Alzheimer's disease. The MCI population actually includes patients with higher risk of progression to AD. Since the new drugs, if effective, will carry both elevated unit costs and not marginal side effects, t...

Background: Glucosylceramidase (GBA) mutations are considered the most common genetic risk factors for developing Parkinson's disease (PD). Objectives: We aimed to assess, at different time points, the integrity of brain striatal and extra-striatal dopamine pathways and clinical phenotype of a group of PD subjects bearing heterozygous GBA mutati...

Underlying neural mechanisms and cognitive implications of non-Rapid Eye Movement (NREM) sleep in isolated REM sleep behavior disorder (iRBD) are not yet fully elucidated. This study aims to evaluate brain metabolic connectivity of the anterior default mode network (ADMN) underlying a waveform that is an hallmark of NREM sleep, namely K-complex (KC...

Visuo-constructive abilities are a multicomponential process that can be impaired in several neurodegenerative dementias. Among visuo-constructive tasks, the Rey-Osterrieth Complex Figure-copy (ROCF-c) is the most commonly used and it seems influenced by different skills mediated by specific brain regions. This task complexity allows exploring diff...

The past decade marked the beginning of the use of resting‐state functional connectivity (RSFC) imaging in bilingualism studies. This paper intends to review the latest evidence of changes in RSFC in language and cognitive control networks in bilinguals during adulthood, aging, and early Alzheimer's disease, which can add to our understanding of br...

Motion perception deficits in dyslexia show a large intersubjective variability, partly reflecting genetic factors influencing brain architecture development. In previous work, we have demonstrated that dyslexic carriers of a mutation of the DCDC2 gene have a very strong impairment in motion perception. In the present study, we investigated structu...

PurposeAn appropriate healthy control dataset is mandatory to achieve good performance in voxel-wise analyses. We aimed at evaluating [18F]FDG PET brain datasets of healthy controls (HC), based on publicly available data, for the extraction of voxel-based brain metabolism maps at the single-subject level.Methods Selection of HC images was based on...

Several radiotracers have been employed to bind amyloid plaques in the brain for the differential diagnosis of neurodegenerative disease, open the possibility to measure in vivo pathogenic processes implicated in Alzheimer disease (AD) and have the potential to detect disease processes at the earliest stages with a potential role in clinical trials...

Cognitive reserve (CR) delays cognitive decline due to neurodegeneration. Heterogeneous evidence suggests that education may act as CR in Dementia with Lewy Bodies (DLB). No data, however, are currently available on the role of occupation as proxy of CR in this neuropathology. Thirty-three patients with probable DLB were retrospectively included. W...

Objective Late-onset amnestic mild cognitive impairment (aMCI) with long disease course and slow progression has been recently recognized as a possible phenotypical expression of a limbic-predominant neurodegenerative disorder. Basic emotion recognition ability crucially depending on temporo-limbic integrity is supposed to be impaired in this group...

Background Preclinical and pathology evidence suggest an involvement of brain dopamine (DA) circuitry in Alzheimer’s Disease (AD). We in vivo investigated, if, when and in which target regions, DA signaling and molecular connectivity are damaged along the AD course. Methods We retrospectively selected 16 amyloid-positive subjects with mild cognitiv...

Accurate and reproducible automated segmentation of human hippocampal subfields is of interest to study their roles in cognitive functions and disease processes. Multispectral structural MRI methods have been proposed to improve automated hippocampal subfield segmentation accuracy, but the reproducibility in a multicentric setting is, to date, not...

PurposeTo know whether mild cognitive impairment (MCI) patients will develop Alzheimer’s disease (AD) dementia in very short time or remain stable is of crucial importance, also considering new experimental drugs usually tested within very short time frames. Here we combined cerebrospinal fluid (CSF) AD biomarkers and a neurodegeneration marker suc...

Background Neuropsychiatric symptoms and cognitive deficits in Alzheimer’s Disease (AD) dementia can be related to changes in the brain dopamine (DA) system. In order to investigate whether and how the DA pathways, namely the nigrostriatal and mesocortico‐limbic, are involved in the pathophysiology of AD, we relied on imaging measures of DA transpo...

Background Pathological reports suggest that dopaminergic and serotonergic pathways are early involved in Alzheimer’s disease (AD). ¹²³ I‐FP‐CIT SPECT imaging allows the evaluation of both dopamine transporter (DAT) and serotonin transporter (SERT) in several brain regions. Method Alzheimer’s disease patients were included in a multicenter study a...