Editorial

3 pages, 227 KiB

Open AccessEditorial

Biomarkers in Alzheimer Disease and Other Dementias: What’s Next into Pathophysiology to Support Clinical Practice and Drug Development

by Anastasia Bougea

Medicina 2022, 58(10), 1374; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina58101374 - 30 Sep 2022

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Abstract

Neurodegenerative diseases are a heterogeneous group of disorders characterized by gradual progressive neuronal loss in the central nervous system [...] Full article

(This article belongs to the Special Issue Biomarkers in Alzheimer Disease and Other Dementias: What’s Next into Pathophysiology to Support Clinical Practice and Drug Development)

Research

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17 pages, 4462 KiB

Open AccessArticle

Silent Pauses and Speech Indices as Biomarkers for Primary Progressive Aphasia

by Constantin Potagas, Zoi Nikitopoulou, Georgia Angelopoulou, Dimitrios Kasselimis, Nikolaos Laskaris, Evie Kourtidou, Vasilios C. Constantinides, Anastasia Bougea, George P. Paraskevas, Georgios Papageorgiou, Dimitrios Tsolakopoulos, Sokratis G. Papageorgiou and Elisabeth Kapaki

Medicina 2022, 58(10), 1352; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina58101352 - 27 Sep 2022

Cited by 5 | Viewed by 1980

Abstract

Background and Objectives: Recent studies highlight the importance of investigating biomarkers for diagnosing and classifying patients with primary progressive aphasia (PPA). Even though there is ongoing research on pathophysiological indices in this field, the use of behavioral variables, and especially speech-derived factors, [...] Read more.

Background and Objectives: Recent studies highlight the importance of investigating biomarkers for diagnosing and classifying patients with primary progressive aphasia (PPA). Even though there is ongoing research on pathophysiological indices in this field, the use of behavioral variables, and especially speech-derived factors, has drawn little attention in the relevant literature. The present study aims to investigate the possible utility of speech-derived indices, particularly silent pauses, as biomarkers for primary progressive aphasia (PPA). Materials and Methods: We recruited 22 PPA patients and 17 healthy controls, from whom we obtained speech samples based on two elicitation tasks, i.e., cookie theft picture description (CTP) and the patients’ personal narration of the disease onset and course. Results: Four main indices were derived from these speech samples: speech rate, articulation rate, pause frequency, and pause duration. In order to investigate whether these indices could be used to discriminate between the four groups of participants (healthy individuals and the three patient subgroups corresponding to the three variants of PPA), we conducted three sets of analyses: a series of ANOVAs, two principal component analyses (PCAs), and two hierarchical cluster analyses (HCAs). The ANOVAs revealed significant differences between the four subgroups for all four variables, with the CTP results being more robust. The subsequent PCAs and HCAs were in accordance with the initial statistical comparisons, revealing that the speech-derived indices for CTP provided a clearer classification and were especially useful for distinguishing the non-fluent variant from healthy participants as well as from the two other PPA taxonomic categories. Conclusions: In sum, we argue that speech-derived indices, and especially silent pauses, could be used as complementary biomarkers to efficiently discriminate between PPA and healthy speakers, as well as between the three variants of the disease. Full article

(This article belongs to the Special Issue Biomarkers in Alzheimer Disease and Other Dementias: What’s Next into Pathophysiology to Support Clinical Practice and Drug Development)

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10 pages, 665 KiB

Open AccessArticle

Initial Data and a Clinical Diagnosis Transition for the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) Study

by Nikolaos Scarmeas, Argyro Daskalaki, Faidra Kalligerou, Eva Ntanasi, Eirini Mamalaki, Antonios N. Gargalionis, Kostas Patas, Stylianos Chatzipanagiotou, Mary Yannakoulia and Vasilios C. Constantinides

Medicina 2022, 58(9), 1179; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina58091179 - 30 Aug 2022

Cited by 4 | Viewed by 1801

Abstract

Background and Objectives: This article presents data from the ongoing Aiginition Longitudinal Biomarker Investigation of Neurodegeneration study (ALBION) regarding baseline clinical characterizations and CSF biomarker profiles, as well as preliminary longitudinal data on clinical progression. Materials and Methods: As of March 2022, 138 [...] Read more.

Background and Objectives: This article presents data from the ongoing Aiginition Longitudinal Biomarker Investigation of Neurodegeneration study (ALBION) regarding baseline clinical characterizations and CSF biomarker profiles, as well as preliminary longitudinal data on clinical progression. Materials and Methods: As of March 2022, 138 participants who either were cognitively normal (CN, n = 99) or had a diagnosis of mild cognitive impairment (MCI, n = 39) had been recruited at the specialist cognitive disorders outpatient clinic at Aiginition Hospital. Clinical characteristics at baseline were provided. These patients were followed annually to determine progression from CN to MCI or even dementia. CSF biomarker data (amyloid β1-42, phosphorylated tau at threonine 181, and total tau) collected using automated Elecsys^® assays (Roche Diagnostics) were available for 74 patients. These patients were further sorted based on the AT(N) classification model, as determined by CSF Aβ42 (A), CSF pTau (T), and CSF tTau (N). Results: Of the 49 CN patients with CSF biomarker data, 21 (43%) were classified as exhibiting “Alzheimer’s pathologic change” (A+Τ– (Ν)−) and 6 (12%) as having “Alzheimer’s disease” (A+T–(N)+, A+T+(N)–, or A+T+(N)+). Of the 25 MCI patients, 8 (32%) displayed “Alzheimer’s pathologic change”, and 6 (24%) had “Alzheimer’s disease”. A total of 66 individuals had a mean follow-up of 2.1 years (SD = 0.9, min = 0.8, max = 3.9), and 15 of those individuals (22%) showed a clinical progression (defined as a worsening clinical classification, i.e., from CN to MCI or dementia or from MCI to dementia). Overall, participants with the “AD continuum” AT(N) biomarker profile (i.e., A+T–(N)–, A+T–(N)+, A+T+(N)–, and A+T+(N)+) were more likely to clinically progress (p = 0.04). Conclusions: A CSF “AD continuum” AT(N) biomarker profile is associated with an increased risk of future clinical decline in CN or MCI subjects. Full article

(This article belongs to the Special Issue Biomarkers in Alzheimer Disease and Other Dementias: What’s Next into Pathophysiology to Support Clinical Practice and Drug Development)

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13 pages, 1854 KiB

Open AccessArticle

Rosinidin Protects Streptozotocin-Induced Memory Impairment-Activated Neurotoxicity by Suppressing Oxidative Stress and Inflammatory Mediators in Rats

by Khalid Saad Alharbi, Muhammad Afzal, Sami I. Alzarea, Shah Alam Khan, Fadhel A. Alomar and Imran Kazmi

Medicina 2022, 58(8), 993; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina58080993 - 26 Jul 2022

Cited by 7 | Viewed by 1513

Abstract

Background and Objectives: To assess the antioxidant and neuroprotective role of rosinidin on rat memory impairment that is induced by streptozotocin. Materials and Methods: Wistar rats were given an intraperitoneal (i.p) injection of streptozotocin (60 mg/kg) followed by treatment with rosinidin [...] Read more.

Background and Objectives: To assess the antioxidant and neuroprotective role of rosinidin on rat memory impairment that is induced by streptozotocin. Materials and Methods: Wistar rats were given an intraperitoneal (i.p) injection of streptozotocin (60 mg/kg) followed by treatment with rosinidin at selective doses (10 and 20 mg/kg) for 30 days. The behavioral parameters were estimated by Y-maze test and Morris water test. Biochemical parameters such as acetylcholinesterase (AChE), choline aacetyltransferase (ChAT), and nitric oxide, and antioxidants such as glutathione transferase (GSH), superoxide dismutase (SOD) IL-6, IL-10, Nrf2, and BDNF, were determined. Results: The study results revealed that rosinidin improved cognition by reverting the behavioral parameters. The treatment with rosinidin restored the antioxidant enzymes and inflammatory cytokines. Conclusions: From the results, it has been proven that rosinidin possesses antioxidant, anti-amnesic, and anti-inflammatory activity. Rosinidin improved the cognitive and behavioral deficits that were induced by streptozotocin. Furthermore, 20 mg/kg rosinidin was found to have strong protective action against streptozotocin-induced toxicity. Full article

(This article belongs to the Special Issue Biomarkers in Alzheimer Disease and Other Dementias: What’s Next into Pathophysiology to Support Clinical Practice and Drug Development)

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9 pages, 313 KiB

Open AccessArticle

Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria

by Daniela Kern, Michael Khalil, Lukas Pirpamer, Arabella Buchmann, Edith Hofer, Peter Dal-Bianco, Elisabeth Stögmann, Christoph Scherfler, Thomas Benke, Gerhard Ransmayr and Reinhold Schmidt

Medicina 2022, 58(3), 433; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina58030433 - 16 Mar 2022

Cited by 5 | Viewed by 2301

Abstract

Background and Objectives: The neurofilament light chain (NfL) is a biomarker for neuro-axonal injury in various acute and chronic neurological disorders, including Alzheimer’s disease (AD). We here investigated the cross-sectional and longitudinal associations between baseline serum NfL (sNfL) levels and cognitive, behavioural [...] Read more.

Background and Objectives: The neurofilament light chain (NfL) is a biomarker for neuro-axonal injury in various acute and chronic neurological disorders, including Alzheimer’s disease (AD). We here investigated the cross-sectional and longitudinal associations between baseline serum NfL (sNfL) levels and cognitive, behavioural as well as MR volumetric findings in the Prospective Dementia Registry Austria (PRODEM-Austria). Materials and Methods: All participants were clinically diagnosed with AD according to NINCDS-ADRDA criteria and underwent a detailed clinical assessment, cognitive testing (including the Mini Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)), the neuropsychiatric inventory (NPI) and laboratory evaluation. A total of 237 patients were included in the study. Follow-up examinations were done at 6 months, 1 year and 2 years with 93.3% of patients undergoing at least one follow-up. We quantified sNfL by a single molecule array (Simoa). In a subgroup of 125 subjects, brain imaging data (1.5 or 3T MRI, with 1 mm isotropic resolution) were available. Brain volumetry was assessed using the FreeSurfer image analysis suite (v6.0). Results: Higher sNfL concentrations were associated with worse performance in cognitive tests at baseline, including CERAD (B = −10.084, SE = 2.999, p < 0.001) and MMSE (B = −3.014, SE = 1.293, p = 0.021). The sNfL levels also correlated with the presence of neuropsychiatric symptoms (NPI total score: r = 0.138, p = 0.041) and with smaller volumes of the temporal lobe (B = −0.012, SE = 0.003, p = 0.001), the hippocampus (B = −0.001, SE = 0.000201, p = 0.013), the entorhinal (B = −0.000308, SE = 0.000124, p = 0.014), and the parahippocampal cortex (B = −0.000316, SE = 0.000113, p = 0.006). The sNfL values predicted more pronounced cognitive decline over the mean follow-up period of 22 months, but there were no significant associations with respect to change in neuropsychiatric symptoms and brain volumetric measures. Conclusions: the sNfL levels relate to cognitive, behavioural, and imaging hallmarks of AD and predicts short term cognitive decline. Full article

(This article belongs to the Special Issue Biomarkers in Alzheimer Disease and Other Dementias: What’s Next into Pathophysiology to Support Clinical Practice and Drug Development)

Review

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19 pages, 2366 KiB

Open AccessReview

Role of Biomarkers for the Diagnosis of Prion Diseases: A Narrative Review

by Miren Altuna, Iñigo Ruiz, María Victoria Zelaya and Maite Mendioroz

Medicina 2022, 58(4), 473; https://doi.org/10.3390/medicina58040473 - 25 Mar 2022

Cited by 5 | Viewed by 3845

Abstract

Prion diseases are progressive and irreversible neurodegenerative disorders with a low incidence (1.5–2 cases per million per year). Genetic (10–15%), acquired (anecdotal) and sporadic (85%) forms of the disease have been described. The clinical spectrum of prion diseases is very varied, although the [...] Read more.

Prion diseases are progressive and irreversible neurodegenerative disorders with a low incidence (1.5–2 cases per million per year). Genetic (10–15%), acquired (anecdotal) and sporadic (85%) forms of the disease have been described. The clinical spectrum of prion diseases is very varied, although the most common symptoms are rapidly progressive dementia, cerebellar ataxia and myoclonus. Mean life expectancy from the onset of symptoms is 6 months. There are currently diagnostic criteria based on clinical phenotype, as well as neuroimaging biomarkers (magnetic resonance imaging), neurophysiological tests (electroencephalogram and polysomnogram), and cerebrospinal fluid biomarkers (14-3-3 protein and real-time quaking-induced conversion (RT-QuIC)). The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) is under debate and the applicability of other tests, such as RT-QuIC, is not universal. However, the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt–Jakob disease, remains unclear. Therefore, research is being carried out on new, more efficient cerebrospinal fluid biomarkers (total tau, ratio total tau/phosphorylated tau and neurofilament light chain) and potential blood biomarkers (neurofilament light chain, among others) to try to universalize access to early diagnosis in the case of prion diseases. Full article

(This article belongs to the Special Issue Biomarkers in Alzheimer Disease and Other Dementias: What’s Next into Pathophysiology to Support Clinical Practice and Drug Development)

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Other

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7 pages, 304 KiB

Open AccessOpinion

Classical Cerebrospinal Fluid Biomarkers in Dementia with Lewy Bodies

by Aikaterini Foska, Ioanna Tsantzali, Eleni Sideri, Maria Ioanna Stefanou, Eleni Bakola, Dimitrios K. Kitsos, Christina Zompola, Anastasios Bonakis, Sotirios Giannopoulos, Konstantinos I. Voumvourakis, Georgios Tsivgoulis and George P. Paraskevas

Medicina 2022, 58(5), 612; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina58050612 - 28 Apr 2022

Cited by 1 | Viewed by 1662

Abstract

The use and interpretation of diagnostic cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders, such as Dementia with Lewy bodies (DLB), represent a clinical challenge. According to the literature, the composition of CSF in DLB patients varies. Some patients present with reduced levels of [...] Read more.

The use and interpretation of diagnostic cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders, such as Dementia with Lewy bodies (DLB), represent a clinical challenge. According to the literature, the composition of CSF in DLB patients varies. Some patients present with reduced levels of amyloid, others with full Alzheimer Disease CSF profile (both reduced amyloid and increased phospho-tau) and some with a normal profile. Some patients may present with abnormal levels of a-synuclein. Continuous efforts will be required to establish useful CSF biomarkers for the early diagnosis of DLB. Given the heterogeneity of methods and results between studies, further validation is fundamental before conclusions can be drawn. Full article

(This article belongs to the Special Issue Biomarkers in Alzheimer Disease and Other Dementias: What’s Next into Pathophysiology to Support Clinical Practice and Drug Development)

13 pages, 1703 KiB

Open AccessSystematic Review

MicroRNA as Candidate Biomarkers in Atypical Parkinsonian Syndromes: Systematic Literature Review

by Anastasia Bougea

Medicina 2022, 58(4), 483; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina58040483 - 26 Mar 2022

Cited by 6 | Viewed by 2456

Abstract

Background and Objectives: Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are rare atypical parkinsonian syndromes, characterized by motor and cognitive symptoms. Their clinical diagnosis is challenging because there are no established biomarkers. Dysregulation of microRNAs (miRNAs/miRs) has been reported to serve [...] Read more.

Background and Objectives: Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are rare atypical parkinsonian syndromes, characterized by motor and cognitive symptoms. Their clinical diagnosis is challenging because there are no established biomarkers. Dysregulation of microRNAs (miRNAs/miRs) has been reported to serve an important role in neurodegenerative diseases. However, the miRNA profiles of MSA and PSP patients are rarely reported. The aim of this study was to critically review the role of miRNAs as diagnostic biomarkers to differentiate these atypical parkinsonian disorders and their role in disease pathogenesis. Materials and Methods: A systematic literature search of PubMed was conducted up to February 2022 according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 15 studies were analyzed. Three studies have shown that miR-9-3p, miR-19a, miR-19b, and miR-24 are potential biomarkers for MSA. In two studies, miR-132 was downregulated, whereas miR-147a and miR-518e were upregulated in the brain tissue of PSP patients. Conclusions: The potential of miRNA is still uncertain as a potential differential diagnostic marker to identify these disorders. Pre-analytical and analytical factors of included studies were important limitations to justify the introduction of miRNAs into clinical practice. Full article

(This article belongs to the Special Issue Biomarkers in Alzheimer Disease and Other Dementias: What’s Next into Pathophysiology to Support Clinical Practice and Drug Development)

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