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Article ; Online: Physical activity, interleukin-6 change, and gait speed.

Panza, Francesco / Custodero, Carlo / Solfrizzi, Vincenzo

Aging

2023 Volume 15, Issue 11, Page(s) 4568–4570

MeSH term(s)	Walking Speed ; Interleukin-6 ; Exercise ; Gait
Chemical Substances	Interleukin-6
Language	English
Publishing date	2023-06-03
Publishing country	United States
Document type	Research Support, N.I.H., Extramural ; Editorial ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.204797
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Article: Passive tau-based immunotherapy for tauopathies.

Panza, Francesco / Solfrizzi, Vincenzo / Daniele, Antonio / Lozupone, Madia

Handbook of clinical neurology

2023 Volume 196, Page(s) 611–619

Abstract: Tauopathies are heterogeneous clinicopathological entities characterized by abnormal neuronal and/or glial inclusions of the microtubule-binding protein tau. In secondary tauopathies, i.e., Alzheimer's disease (AD), tau deposition can be observed, but ... ...

Abstract	Tauopathies are heterogeneous clinicopathological entities characterized by abnormal neuronal and/or glial inclusions of the microtubule-binding protein tau. In secondary tauopathies, i.e., Alzheimer's disease (AD), tau deposition can be observed, but tau may coexist with another protein, i.e., amyloid-β. In the last 20 years, little progress has been made in developing disease-modifying drugs for primary and secondary tauopathies and available symptomatic drugs have limited efficacy. Treatments are being developed to interfere with the aggregation process or to promote the clearance of tau protein. Several tau-targeted passive immunotherapy approaches are in development for treating tauopathies. At present, 12 anti-tau antibodies have entered clinical trials, and 7 of them are still in clinical testing for primary tauopathies and AD (semorinemab, bepranemab, E2814, JNJ-63733657, Lu AF87908, PNT00, and APNmAb005). However, none of these seven agents have reached Phase III. The most advanced anti-tau monoclonal antibody for treating AD is semorinemab, while bepranemab is the only anti-tau monoclonal antibody still in clinical testing for treating progressive supranuclear palsy syndrome. Two other anti-tau monoclonal antibodies have been discontinued for the treatment of primary tauopathies, i.e., gosuranemab and tilavonemab. Further evidence will come from ongoing Phase I/II trials on passive immunotherapeutics for treating primary and secondary tauopathies.
MeSH term(s)	Humans ; tau Proteins ; Tauopathies/therapy ; Alzheimer Disease ; Antibodies, Monoclonal ; Immunization, Passive
Chemical Substances	tau Proteins ; Antibodies, Monoclonal
Language	English
Publishing date	2023-07-14
Publishing country	Netherlands
Document type	Review ; Journal Article
ISSN	0072-9752
ISSN	0072-9752
DOI	10.1016/B978-0-323-98817-9.00029-6
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Article ; Online: How can we manage progressive supranuclear palsy syndrome with pharmacotherapy?

Lozupone, Madia / Dibello, Vittorio / Daniele, Antonio / Solfrizzi, Vincenzo / Resta, Emanuela / Panza, Francesco

Expert opinion on pharmacotherapy

2024 , Page(s) 1–14

Abstract: Introduction: Tauopathies are a spectrum of clinicopathological neurodegenerative disorders with increased aggregates included in glia and/or neurons of hyperphosphorylated insoluble tau protein, a microtubule-associated protein. Progressive ... ...

Abstract	Introduction: Tauopathies are a spectrum of clinicopathological neurodegenerative disorders with increased aggregates included in glia and/or neurons of hyperphosphorylated insoluble tau protein, a microtubule-associated protein. Progressive supranuclear palsy (PSP) is an atypical dopaminergic-resistant parkinsonian syndrome, considered as a primary tauopathy with possible alteration of tau isoform ratio, and tau accumulations characterized by 4 R tau species as the main neuropathological lesions. Areas covered: In the present review article, we analyzed and discussed viable disease-modifying and some symptomatic pharmacological therapeutics for PSP syndrome (PSPS). Expert opinion: Pharmacological therapy for PSPS may interfere with the aggregation process or promote the clearance of abnormal tau aggregates. A variety of past and ongoing disease-modifying therapies targeting tau in PSPS included genetic, microtubule-stabilizing compounds, anti-phosphorylation, and acetylation agents, antiaggregant, protein removal, antioxidant neuronal and synaptic growth promotion therapies. New pharmacological gene-based approaches may open alternative prevention pathways for the deposition of abnormal tau in PSPS such as antisense oligonucleotide (ASO)-based drugs. Moreover, kinases and ubiquitin-proteasome systems could also be viable targets.
Language	English
Publishing date	2024-04-27
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2024.2345734
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Zs.A 5130: Show issues

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Article: When Inappropriate Use of Insulin is Dangerous: The Utility of C-Peptide Assay in the Era of Cardioprotective Antidiabetic Drugs.

Volpe, Sara / Tortorella, Cosimo / Solfrizzi, Vincenzo / Piazzolla, Giuseppina

Diabetes, metabolic syndrome and obesity : targets and therapy

2021 Volume 14, Page(s) 3517–3521

Abstract: Introduction: New antidiabetic drugs have simplified treatment regimens in patients with type-2 diabetes (T2D). More importantly, they have proven to reduce cardiovascular risk by lowering insulin-resistance, blood pressure and body weight, in addition ... ...

Abstract	Introduction: New antidiabetic drugs have simplified treatment regimens in patients with type-2 diabetes (T2D). More importantly, they have proven to reduce cardiovascular risk by lowering insulin-resistance, blood pressure and body weight, in addition to avoiding inappropriate insulin therapy, responsible for hypoglycemic episodes and weight gain. In this context, accurate assessment of the metabolic status of T2D patients becomes essential. The C-peptide assay is a simple but often overlooked test that can provide a fundamental contribution to the correct disease classification and optimal therapeutic management of diabetic patients. Clinical case: We report the case of a 72-year-old patient, treated with insulin for 26 years after a diagnosis of type-1 diabetes (T1D), resulting in inadequate glycemia control and a severe evolution of cardiovascular complications. After an accurate evaluation of the clinical history, phenotype and laboratory data, including the determination of C-peptide serum levels, a diagnosis was made of T2D not T1D. Considering the patient's very high cardiovascular risk and dysmetabolic profile, insulin therapy was discontinued and more appropriate therapy with dulaglutide and metformin was instituted. These overall therapeutic modifications yielded remarkable clinical advantages in terms of the glycometabolic profile, weight reduction, abdominal circumference and body mass index decrease, as well as a better quality of life, with complete resolution of the dangerous hypoglycemic episodes. Conclusion: In the era of new cardioprotective antidiabetic drugs, we believe the importance of the C-peptide assay should be re-evaluated in order to avoid misdiagnosis and to improve the therapeutic approach to T2D.
Language	English
Publishing date	2021-08-05
Publishing country	New Zealand
Document type	Case Reports
ZDB-ID	2494854-8
ISSN	1178-7007
ISSN	1178-7007
DOI	10.2147/DMSO.S321340
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Article: Carotenoids and Cognitive Outcomes: A Meta-Analysis of Randomized Intervention Trials.

Davinelli, Sergio / Ali, Sawan / Solfrizzi, Vincenzo / Scapagnini, Giovanni / Corbi, Graziamaria

Antioxidants (Basel, Switzerland)

2021 Volume 10, Issue 2

Abstract: Recent evidence suggests that diet can modify the risk of future cognitive impairment and dementia. A biologically plausible rationale and initial clinical data indicate that the antioxidant activities of dietary carotenoids may assist the preservation ... ...

Abstract	Recent evidence suggests that diet can modify the risk of future cognitive impairment and dementia. A biologically plausible rationale and initial clinical data indicate that the antioxidant activities of dietary carotenoids may assist the preservation of cognitive function. A meta-analysis of randomized controlled trials was conducted to examine the relationship between carotenoid supplementation and cognitive performance. A literature search was conducted in the MEDLINE (via PubMed), Scopus, Web of Science, and Cochrane databases from their inception to July 2020. A total of 435 studies were retrieved. Abstract screening using predefined inclusion and exclusion criteria was followed by full-text screening and data extraction of study characteristics and measured outcomes. A meta-analysis of eligible trials was performed using a random-effects model to estimate pooled effect size. We identified 9 studies with a total of 4402 nondemented subjects, whose age ranged from 45 to 78 years. Results of the pooled meta-analysis found a significant effect of carotenoid intervention on cognitive outcomes (Hedge's g = 0.14; 95% confidence interval: 0.08, 0.20,
Language	English
Publishing date	2021-02-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10020223
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Article ; Online: Frailty and outcome after traumatic brain injury.

Panza, Francesco / Sardone, Rodolfo / Dibello, Vittorio / Daniele, Antonio / Solfrizzi, Vincenzo / Lozupone, Madia

The Lancet. Neurology

2022 Volume 21, Issue 2, Page(s) 107–108

MeSH term(s)	Brain Injuries, Traumatic/therapy ; Frailty ; Humans
Language	English
Publishing date	2022-01-20
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2081241-3
ISSN	1474-4465 ; 1474-4422
ISSN (online)	1474-4465
ISSN	1474-4422
DOI	10.1016/S1474-4422(21)00418-X
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Zs.A 5955: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: The epigenetics of frailty.

Lozupone, Madia / Solfrizzi, Vincenzo / Sardone, Rodolfo / Dibello, Vittorio / Castellana, Fabio / Zupo, Roberta / Lampignano, Luisa / Bortone, Ilaria / Daniele, Antonio / Panza, Francesco

Epigenomics

2023 Volume 16, Issue 3, Page(s) 189–202

Abstract: The conceptual change of frailty, from a physical to a biopsychosocial phenotype, expanded the field of frailty, including social and behavioral domains with critical interaction between different frailty models. Environmental exposures - including ... ...

Abstract	The conceptual change of frailty, from a physical to a biopsychosocial phenotype, expanded the field of frailty, including social and behavioral domains with critical interaction between different frailty models. Environmental exposures - including physical exercise, psychosocial factors and diet - may play a role in the frailty pathophysiology. Complex underlying mechanisms involve the progressive interactions of genetics with epigenetics and of multimorbidity with environmental factors. Here we review the literature on possible mechanisms explaining the association between epigenetic hallmarks (i.e., global DNA methylation, DNA methylation age acceleration and microRNAs) and frailty, considered as biomarkers of aging. Frailty could be considered the result of environmental epigenetic factors on biological aging, caused by conflicting DNA methylation age and chronological age.
MeSH term(s)	Humans ; Frailty/genetics ; Epigenesis, Genetic ; Aging/genetics ; DNA Methylation ; MicroRNAs/genetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2023-12-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2537199-X
ISSN	1750-192X ; 1750-1911
ISSN (online)	1750-192X
ISSN	1750-1911
DOI	10.2217/epi-2023-0279
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Article ; Online: Effect of Physical Activity Intervention on Gait Speed by Frailty Condition: A Randomized Clinical Trial.

Custodero, Carlo / Agosti, Pasquale / Anton, Stephen D / Manini, Todd M / Lozupone, Madia / Panza, Francesco / Pahor, Marco / Sabbà, Carlo / Solfrizzi, Vincenzo

Journal of the American Medical Directors Association

2023 Volume 24, Issue 4, Page(s) 489–496

Abstract: Objectives: There is uncertainty about effects of physical activity on physical performance, such as gait speed, among community-dwelling older adults according to their physical frailty status. We determined whether a long-term, moderate-intensity ... ...

Abstract	Objectives: There is uncertainty about effects of physical activity on physical performance, such as gait speed, among community-dwelling older adults according to their physical frailty status. We determined whether a long-term, moderate-intensity physical activity program was associated with different responses on gait speed over 4 m and 400 m based on physical frailty status. Design: Post hoc analysis from the Lifestyle Interventions and Independence for Elders (LIFE) (NCT01072500), a single-blind randomized clinical trial testing the effect of physical activity intervention compared with health education program. Setting and participants: We analyzed data on 1623 community-dwelling older adults (78.9 ± 5.2 years) at risk for mobility disability. Methods: Physical frailty was assessed at baseline using the Study of Osteoporotic Fractures frailty index. Gait speed over 4 m and 400 m was measured at baseline, and 6, 12, and 24 months. Results: We estimated significantly better 400-m gait speed at 6, 12, and 24 months for nonfrail older adults in the physical activity group, but not for frail participants. Among frail participants, physical activity showed a potentially clinically meaningful benefit on 400-m gait speed at 6 months (0.055; 95% CI 0.016-0.094; P = .005), compared with the healthy educational intervention, only in those who, at baseline, were able to rise from a chair 5 times without using their arms. Conclusions and implications: A well-structured physical activity program produced a faster 400-m gait speed potentially able to prevent mobility disability among physically frail individuals with preserved muscle strength in lower limbs.
MeSH term(s)	Humans ; Aged ; Frailty ; Walking Speed ; Single-Blind Method ; Exercise ; Life Style ; Frail Elderly
Language	English
Publishing date	2023-03-03
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2171030-2
ISSN	1538-9375 ; 1525-8610
ISSN (online)	1538-9375
ISSN	1525-8610
DOI	10.1016/j.jamda.2023.01.023
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Zs.A 5971: Show issues

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Article ; Online: Lessons learned from the failure of solanezumab as a prospective treatment strategy for Alzheimer's disease.

Lozupone, Madia / Dibello, Vittorio / Sardone, Rodolfo / Castellana, Fabio / Zupo, Roberta / Lampignano, Luisa / Bortone, Ilaria / Stallone, Roberta / Altamura, Mario / Bellomo, Antonello / Daniele, Antonio / Solfrizzi, Vincenzo / Panza, Francesco

Expert opinion on drug discovery

2024 , Page(s) 1–9

Abstract: Introduction: In the last decade, the efforts conducted for discovering Alzheimer's Disease (AD) treatments targeting the best-known pathogenic factors [amyloid-β (Aβ), tau protein, and neuroinflammation] were mostly unsuccessful. Given that a systemic ... ...

Abstract	Introduction: In the last decade, the efforts conducted for discovering Alzheimer's Disease (AD) treatments targeting the best-known pathogenic factors [amyloid-β (Aβ), tau protein, and neuroinflammation] were mostly unsuccessful. Given that a systemic failure of Aβ clearance was supposed to primarily contribute to AD development and progression, disease-modifying therapies with anti-Aβ monoclonal antibodies (e.g. solanezumab, bapineuzumab, gantenerumab, aducanumab, lecanemab and donanemab) are ongoing in randomized clinical trials (RCTs) with contrasting results. Areas covered: The present Drug Discovery Case History analyzes the failures of RCTs of solanezumab on AD. Furthermore, the authors review the pharmacokinetics, pharmacodynamics, and tolerability effect of solanezumab from preclinical studies with its analogous m266 in mice. Finally, they describe the RCTs with cognitive, cerebrospinal fluid and neuroimaging findings in mild-to-moderate AD (EXPEDITION studies) and in secondary prevention studies (A4 and DIAN-TU). Expert opinion: Solanezumab was one of the first anti-Aβ monoclonal antibodies to be tested in preclinical and clinical AD showing to reduce brain Aβ level by acting on soluble monomeric form of Aβ peptide without significant results on deposits. Unfortunately, this compound showed to accelerate cognitive decline in both asymptomatic and symptomatic trial participants, and this failure of solanezumab further questioned the Aβ cascade hypothesis of AD.
Language	English
Publishing date	2024-04-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2259618-5
ISSN	1746-045X ; 1746-0441
ISSN (online)	1746-045X
ISSN	1746-0441
DOI	10.1080/17460441.2024.2348142
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Zs.A 6388: Show issues

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Article ; Online: Effectiveness and clinical benefits of new anti-diabetic drugs

Piazzolla Giuseppina / Vozza Alfredo / Volpe Sara / Bergamasco Alessandro / Triggiani Vincenzo / Lisco Giuseppe / Falconieri Michela / Tortorella Cosimo / Solfrizzi Vincenzo / Sabbà Carlo

Open Medicine, Vol 17, Iss 1, Pp 1203-

A real life experience

2022 Volume 1215

Abstract: We evaluated the clinical impact, in daily clinical practice, of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) therapies in patients with type 2 diabetes. Data from 500 unselected consecutive ... ...

Abstract	We evaluated the clinical impact, in daily clinical practice, of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) therapies in patients with type 2 diabetes. Data from 500 unselected consecutive patients were retrospectively analyzed. Only those with a full assessment at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment with SGLT2i or GLP1RA were included in the study (n = 167). At baseline, patients had a high mean body weight (BW), abdominal circumference (AC), body mass index (BMI), and HOMA index. Despite normal C-peptide values, 39 patients were being treated with insulin (up to 120 IU/day). During therapy, a progressive improvement in BW, BMI, and AC was observed with both the molecules. Fasting glucose and glycated Hb decrease was already significant at T3 in all patients, while the HOMA index selectively improved with SGLT2i therapy. Renal function parameters remained stable regardless of the drug used. Finally, SGLT2i reduced serum uric acid and improved the lipid profile, while GLP1RA reduced serum levels of liver enzymes. Both the therapeutic regimens allowed a significant reduction or complete suspension of unnecessary insulin therapies. Our real life data confirm the results obtained from randomized clinical trials and should be taken as a warning against inappropriate use of insulin in patients with preserved β-cell function.
Keywords	sglt2i ; glp1ra ; type 2 diabetes ; c-peptide ; insulin therapy ; Medicine ; R
Subject code	610 ; 616
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	De Gruyter
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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