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Article ; Online: Advances in the treatment and management of frontotemporal dementia.

Benussi, Alberto / Borroni, Barbara

2023 Volume 23, Issue 7, Page(s) 621–639

Abstract: Introduction: Frontotemporal dementia (FTD) is a complex neurodegenerative disorder, characterized by a wide range of pathological conditions associated with the buildup of proteins such as tau and TDP-43. With a strong hereditary component, FTD often ... ...

Abstract	Introduction: Frontotemporal dementia (FTD) is a complex neurodegenerative disorder, characterized by a wide range of pathological conditions associated with the buildup of proteins such as tau and TDP-43. With a strong hereditary component, FTD often results from genetic variants in three genes - Areas covered: In this review, the authors explore abnormal protein accumulation in FTD and forthcoming treatments, providing a detailed analysis of new diagnostic advancements, including innovative markers. They analyze how these discoveries have influenced therapeutic strategies, particularly disease-modifying treatments, which could potentially transform FTD management. This comprehensive exploration of FTD from its molecular underpinnings to its therapeutic prospects offers a compelling overview of the current state of FTD research. Expert opinion: Notable challenges in FTD management involve identifying reliable biomarkers for early diagnosis and response monitoring. Genetic forms of FTD, particularly those linked to
MeSH term(s)	Humans ; Frontotemporal Dementia/diagnosis ; Frontotemporal Dementia/genetics ; Frontotemporal Dementia/therapy ; C9orf72 Protein/genetics ; Mutation ; tau Proteins ; Biomarkers ; Psychotherapy
Chemical Substances	C9orf72 Protein ; tau Proteins ; Biomarkers
Language	English
Publishing date	2023-06-26
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2112534-X
ISSN	1744-8360 ; 1473-7175
ISSN (online)	1744-8360
ISSN	1473-7175
DOI	10.1080/14737175.2023.2228491
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Article ; Online: Neuropsychiatric Symptoms in Frontotemporal Dementia: More Than Just Noise?

Altomare, Daniele / Rivolta, Jasmine / Libri, Ilenia / Mattioli, Irene / Cantoni, Valentina / Padovani, Alessandro / Borroni, Barbara

Journal of Alzheimer's disease : JAD

2024 Volume 98, Issue 1, Page(s) 133–144

Abstract: Background: Neuropsychiatric symptoms cause significant suffering and poor quality of life for patients and their caregivers. They are not considered specific to frontotemporal dementia (FTD); therefore, their clinical role and impact might be ... ...

Abstract	Background: Neuropsychiatric symptoms cause significant suffering and poor quality of life for patients and their caregivers. They are not considered specific to frontotemporal dementia (FTD); therefore, their clinical role and impact might be underestimated. Objective: The aims of the present study are to: 1) describe the prevalence of neuropsychiatric symptoms in FTD starting from the prodromal stage, 2) define their association with disease severity, 3) identify symptoms which are unrelated to FTD-specific symptoms, and 4) assess their association with clinical features and outcomes. Results: In this retrospective study, we analyzed data of 461 FTD patients, including behavioral variant of FTD (bvFTD, n = 318) and primary progressive aphasia (PPA, n = 143). Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory, and patients' staging and global disease severity were estimated using the Clinical Dementia Rating plus NACC FTLD. Results: The most common neuropsychiatric symptoms in prodromal FTD were irritability (48%), depression (35%), and anxiety (34%); delusions were reported in 6%of prodromal bvFTD cases. The severity of most neuropsychiatric symptoms increased with global disease severity. Psychosis (delusions and hallucinations) and mood symptoms (depression and anxiety) were mostly independent from FTD-specific symptoms. Psychosis was associated with older age, higher disease severity, shorter survival rate, and was higher in bvFTD than in PPA. Conclusions: Neuropsychiatric symptoms are common in patients with FTD, also in the prodromal phase. Psychosis might be unrelated to FTD pathology, and be associated with worse clinical outcomes. The prompt detection and treatment of these symptoms might improve patient's management and quality of life.
MeSH term(s)	Humans ; Frontotemporal Dementia/psychology ; Retrospective Studies ; Quality of Life ; Neuropsychological Tests ; Psychotic Disorders
Language	English
Publishing date	2024-02-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-231256
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Article ; Online: Lessons from the past to understand the future.

Leys, Didier / Sommer, Claudia / Borroni, Barbara / Chan, Andrew / Edwards, Mark / Tessitore, Alessandro / Vonck, Kristl

European journal of neurology

2024 , Page(s) e16270

Language	English
Publishing date	2024-03-05
Publishing country	England
Document type	Editorial
ZDB-ID	1280785-0
ISSN	1468-1331 ; 1351-5101 ; 1471-0552
ISSN (online)	1468-1331
ISSN	1351-5101 ; 1471-0552
DOI	10.1111/ene.16270
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Article ; Online: Dissecting the Many Faces of Frontotemporal Dementia: An Imaging Perspective.

Pengo, Marta / Premi, Enrico / Borroni, Barbara

International journal of molecular sciences

2022 Volume 23, Issue 21

Abstract: Frontotemporal dementia (FTD) is a heterogeneous clinical and neuropathological disorder characterized by behavioral abnormalities, executive dysfunctions and language deficits. FTD encompasses a wide range of different pathological entities, associated ... ...

Abstract	Frontotemporal dementia (FTD) is a heterogeneous clinical and neuropathological disorder characterized by behavioral abnormalities, executive dysfunctions and language deficits. FTD encompasses a wide range of different pathological entities, associated with the accumulation of proteins, such as tau and TPD-43. A family history of dementia is found in one third of cases, and several genes causing autosomal dominant inherited disease have been identified. The clinical symptoms are preceded by a prodromal phase, which has been mainly studied in cases carrying pathogenetic mutations. New experimental strategies are emerging, in both prodromal and clinical settings, and outcome markers are needed to test their efficacy. In this complex context, in the last few years, advanced neuroimaging techniques have allowed a better characterization of FTD, supporting clinical diagnosis, improving the comprehension of genetic heterogeneity and the earliest stages of the disease, contributing to a more detailed classification of underlying proteinopathies, and developing new outcome markers on clinical grounds. In this review, we briefly discuss the contribution of brain imaging and the most recent techniques in deciphering the different aspects of FTD.
MeSH term(s)	Humans ; Frontotemporal Dementia/diagnostic imaging ; Frontotemporal Dementia/genetics ; Pick Disease of the Brain/pathology ; Neuroimaging ; Brain/metabolism ; Mutation ; Biomarkers ; tau Proteins/metabolism
Chemical Substances	Biomarkers ; tau Proteins
Language	English
Publishing date	2022-10-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232112867
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Article ; Online: Legal issues in frontotemporal dementia: aspects still neglected in court and clinical practice.

Invernizzi, Laura / Marcone, Alessandra / Alberici, Antonella / Borroni, Barbara

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2021 Volume 42, Issue 11, Page(s) 4847–4848

MeSH term(s)	Frontotemporal Dementia ; Humans
Language	English
Publishing date	2021-09-20
Publishing country	Italy
Document type	Letter
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-021-05593-5
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Article ; Online: Recent advances in understanding frontotemporal degeneration.

Borroni, Barbara / Benussi, Alberto

F1000Research

2019 Volume 8

Abstract: Frontotemporal degeneration (FTD) is a heterogeneous spectrum of neurodegenerative disorders characterized by diverse clinical presentations, neuropathological characteristics, and underlying genetic causes. In the last few years, several advances in the ...

Abstract	Frontotemporal degeneration (FTD) is a heterogeneous spectrum of neurodegenerative disorders characterized by diverse clinical presentations, neuropathological characteristics, and underlying genetic causes. In the last few years, several advances in the knowledge of clinical and biological aspects have been accomplished and three major scenarios have emerged that will represent the core issues in the FTD scene over the next few years. Foremost, the development of cerebrospinal fluid and blood biomarkers as well as neuroimaging techniques will aid the pursuit of new diagnostic and prognostic markers able to identify the ongoing proteinopathy and predict disease progression, which is key in identifying and stratifying patients for enrolment in clinical trials as well as evaluating response to treatment. On the other hand, current research has focused on the first attempts to slow down or revert disease progression, with the identification of disease modulators associated with disease onset and the ongoing development of the first pharmacological treatments for both sporadic and genetic FTD. Future research will certainly improve our knowledge of FTD and possibly open up a new era of disease-modifying therapies for this still-orphan disorder.
MeSH term(s)	Atrophy ; Biomarkers ; Humans ; Neurodegenerative Diseases ; Neuroimaging
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-12-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.20330.1
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Article ; Online: Author response: Cerebello-spinal tDCS in ataxia: A randomized, double-blind, sham-controlled, crossover trial.

Benussi, Alberto / Borroni, Barbara

Neurology

2019 Volume 92, Issue 23, Page(s) 1122

MeSH term(s)	Ataxia ; Cerebellar Ataxia ; Cross-Over Studies ; Double-Blind Method ; Humans ; Transcranial Direct Current Stimulation
Language	English
Publishing date	2019-06-03
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000007625
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Article ; Online: Plasma biomarkers increase diagnostic confidence in patients with Alzheimer's disease or frontotemporal lobar degeneration.

Altomare, Daniele / Libri, Ilenia / Alberici, Antonella / Rivolta, Jasmine / Padovani, Alessandro / Ashton, Nicholas J / Zetterberg, Henrik / Blennow, Kaj / Borroni, Barbara

Alzheimer's research & therapy

2024 Volume 16, Issue 1, Page(s) 107

Abstract: Background: The recent development of techniques to assess plasma biomarkers has changed the way the research community envisions the future of diagnosis and management of Alzheimer's disease (AD) and other neurodegenerative disorders. This work aims to ...

Abstract	Background: The recent development of techniques to assess plasma biomarkers has changed the way the research community envisions the future of diagnosis and management of Alzheimer's disease (AD) and other neurodegenerative disorders. This work aims to provide real world evidence on the clinical impact of plasma biomarkers in an academic tertiary care center. Methods: Anonymized clinical reports of patients diagnosed with AD or Frontotemporal Lobar Degeneration with available plasma biomarkers (Aβ Results: Clinicians assessed 122 reports, and their concordance ranged from 81 to 91% at the three time points. At T1, the presentation of plasma biomarkers resulted in a change of diagnosis in 2% (2/122, p = 1.00) of cases, and in increased diagnostic confidence in 76% (91/120, p < 0.001) of cases with confirmed diagnosis. The change in diagnosis and the increase in diagnostic confidence after plasma biomarkers were consistent with the final diagnosis in 100% (2/2) and 81% (74/91) of cases, respectively. At T2, the presentation of traditional biomarkers resulted in a further change of diagnosis in 13% (12/94, p = 0.149) of cases, and in increased diagnostic confidence in 88% (72/82, p < 0.001) of cases with confirmed diagnosis. Conclusions: In an academic tertiary care center, plasma biomarkers supported clinicians by increasing their diagnostic confidence in most cases, despite a negligible impact on diagnosis. Future prospective studies are needed to assess the full potential of plasma biomarkers on clinical grounds.
MeSH term(s)	Humans ; Alzheimer Disease/blood ; Alzheimer Disease/diagnosis ; Biomarkers/blood ; Frontotemporal Lobar Degeneration/blood ; Frontotemporal Lobar Degeneration/diagnosis ; Amyloid beta-Peptides/blood ; tau Proteins/blood ; Female ; Male ; Aged ; Peptide Fragments/blood ; Middle Aged ; Neurofilament Proteins/blood
Chemical Substances	Biomarkers ; Amyloid beta-Peptides ; tau Proteins ; Peptide Fragments ; amyloid beta-protein (1-42) ; Neurofilament Proteins ; neurofilament protein L
Language	English
Publishing date	2024-05-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-024-01474-z
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Article ; Online: Association of APOE genotype with blood-brain barrier permeability in neurodegenerative disorders.

Libri, Ilenia / Silvestri, Chiara / Caratozzolo, Salvatore / Alberici, Antonella / Pilotto, Andrea / Archetti, Silvana / Trainini, Laura / Borroni, Barbara / Padovani, Alessandro / Benussi, Alberto

Neurobiology of aging

2024 Volume 140, Page(s) 33–40

Abstract: Apolipoprotein E (APOE) is recognized for its role in modulating blood-brain barrier (BBB) permeability in vitro, which may have significant implications for the pathogenesis and progression of neurodegenerative disorders. However, evidence in vivo is ... ...

Abstract	Apolipoprotein E (APOE) is recognized for its role in modulating blood-brain barrier (BBB) permeability in vitro, which may have significant implications for the pathogenesis and progression of neurodegenerative disorders. However, evidence in vivo is contrasting. This study explores the impact of APOE genotypes on BBB integrity among 230 participants experiencing cognitive impairment, encompassing cases of Alzheimer's disease (AD) as well as various non-AD neurodegenerative conditions. To assess BBB integrity, we utilized cerebrospinal fluid (CSF)/serum albumin ratios and CSF/serum kappa and lambda free light chains (FLCs) as indirect markers. Our findings show a dose-dependent increase in BBB permeability in individuals carrying the APOE ε4 allele, marked by elevated CSF/serum albumin and FLCs ratios, with this trend being especially pronounced in AD patients. These results highlight the association of APOE ε4 with BBB permeability, providing valuable insights into the pathophysiology of neurodegenerative diseases.
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2024.04.003
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Article ; Online: Time to Diagnosis and Its Predictors in Syndromes Associated With Frontotemporal Lobar Degeneration.

Libri, Ilenia / Altomare, Daniele / Bracca, Valeria / Rivolta, Jasmine / Cantoni, Valentina / Mattioli, Irene / Alberici, Antonella / Borroni, Barbara

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry

2024

Abstract: Objectives: Frontotemporal Lobar Degeneration (FTLD) causes a heterogeneous group of neurodegenerative disorders with a wide range of clinical features. This might delay time to diagnosis. The aim of the present study is to establish time to diagnosis ... ...

Abstract	Objectives: Frontotemporal Lobar Degeneration (FTLD) causes a heterogeneous group of neurodegenerative disorders with a wide range of clinical features. This might delay time to diagnosis. The aim of the present study is to establish time to diagnosis and its predictors in patients with FTLD-associated syndromes. Design: Retrospective study. Setting: Tertiary referral center. Participants: A total of 1029 patients with FTLD-associated syndromes (age: 68 [61-73] years, females: 46%) from 1999 to 2023 were included in the present study. Measurements: Time to diagnosis was operationalized as the time between symptom onset and the diagnosis of a FTLD-associated syndrome. The associations between time to diagnosis and possible predictors (demographic and clinical variables) were investigated through univariate and multivariate linear models. Results: Median time to diagnosis was 2 [1-3] years. We observed that younger age at onset (β = -0.03, p <0.001), having worked as a professional rather than as a blue (β = 0.52, p = 0.024) or a white (β = 0.46, p = 0.050) collar, and having progressive supranuclear palsy (p <0.05) or the semantic variant of primary progressive aphasia (p <0.05) phenotypes were significantly associated with increased time to diagnosis. No significant changes of time to diagnosis have been observed over 20 years. Conclusions: The identification of predictors of time to diagnosis might improve current diagnostic algorithms, resulting in a timely initiation of symptomatic treatments, early involvement in clinical trials, and more adequate public health policies for patients and their families.
Language	English
Publishing date	2024-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	1278145-9
ISSN	1545-7214 ; 1064-7481
ISSN (online)	1545-7214
ISSN	1064-7481
DOI	10.1016/j.jagp.2024.03.002
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