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From Molecules to Cognition: Biomarkers and Neuropsychological Tools in Neurological Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 December 2026 | Viewed by 2253

Special Issue Editor

Dr. Silvia Boschi

E-Mail Website
Guest Editor
Aging Brain and Memory Clinic, Department of Neuroscience, “Rita Levi Montalcini”, Memory Clinic, University of Torino, Via Cherasco 15, 10126 Turin, Italy
Interests: Alzheimer’s disease; dementia; neurodegeneration; neuronal biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurological disorders remain a leading cause of disability worldwide, with complex and heterogeneous clinical manifestations. Reliable biomarkers and standardized neuropsychological assessments are crucial for improving early diagnosis, guiding prognosis, and tailoring personalized therapeutic strategies. Recent advances in molecular biology, neuroimaging, and digital health technologies provide new opportunities to better characterize disease mechanisms and improve patient outcomes.

This Special Issue aims to bring together original research articles and reviews focused on the discovery and validation of biomarkers, as well as the development and application of neuropsychological tools, across a wide range of neurological conditions. Contributions that integrate molecular, cognitive, and clinical perspectives are particularly welcome.

Dr. Silvia Boschi
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • biomarkers
  • neuropsychological assessment
  • neurological disorders
  • neuroimaging
  • cognitive function
  • translational neuroscience

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Published Papers (3 papers)

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Research

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15 pages, 748 KB  
Article
Role of the Clock Drawing Test in Differential Diagnosis of Alzheimer’s Disease: Clinical Findings in Relation to CSF Biomarkers
by Aurora Cermelli, Chiara Lombardo, Alberto Mario Chiarandon, Fausto Roveta, Elisa Maria Piella, Virginia Batti, Elisa Rubino, Innocenzo Rainero and Silvia Boschi
Int. J. Mol. Sci. 2026, 27(4), 1790; https://doi.org/10.3390/ijms27041790 - 13 Feb 2026
Viewed by 660
Abstract
Alzheimer’s disease (AD) is the most common cause of neurocognitive disorder, and the integration of cognitive assessment with biological markers remains essential for clinical characterization. The Clock Drawing Test (CDT) is a brief and widely used screening tool assessing visuospatial and executive functions, [...] Read more.
Alzheimer’s disease (AD) is the most common cause of neurocognitive disorder, and the integration of cognitive assessment with biological markers remains essential for clinical characterization. The Clock Drawing Test (CDT) is a brief and widely used screening tool assessing visuospatial and executive functions, which may reflect underlying neurodegenerative processes. This study investigated the diagnostic performance of the CDT and its association with cerebrospinal fluid (CSF) biomarkers within the A/T/(N) research framework. Ninety-seven patients with mild or major neurocognitive disorder were classified as AD or non-AD according to CSF amyloid-β, phosphorylated tau, and total tau profiles, and compared with 36 healthy participants. All subjects underwent a comprehensive neuropsychological evaluation, including the CDT scored using the quantitative–qualitative method proposed by Rouleau et al. Group comparisons, ROC analyses, and regression models adjusted for age, sex, and education were performed. CDT scores effectively distinguished patients from healthy participants, showing large effect sizes, and modestly differentiated AD from non-AD profiles, particularly on the Hands subscale. Diagnostic accuracy was fair, with adjusted AUC values ranging from 0.65 to 0.75. Lower CDT performance was significantly associated with higher CSF total tau levels, while associations with amyloid-β and phosphorylated tau were not robust after correction. These findings suggest that the CDT is sensitive to cognitive impairment severity and shows limited but meaningful relationships with neurodegenerative biomarkers, supporting its role as a practical complementary tool alongside biological assessment. Full article
(This article belongs to the Special Issue From Molecules to Cognition: Biomarkers and Neuropsychological Tools in Neurological Disorders)
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Review

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31 pages, 1190 KB  
Review
Theranostic Nanoplatforms for Alzheimer’s Disease: A Critical Analysis of Conceptual Contradictions
by Yana Zorkina, Olga Abramova, Eugene Zubkov, Olga Gurina and Valeriya Ushakova
Int. J. Mol. Sci. 2026, 27(8), 3560; https://doi.org/10.3390/ijms27083560 - 16 Apr 2026
Viewed by 307
Abstract
Alzheimer’s disease (AD) remains an incurable neurodegenerative disorder. The concept of theranostics—combining diagnostic and therapeutic functions within a single nanoplatform—has been explored for over a decade. Despite a growing number of publications, no theranostic system has yet reached clinical application for AD. This [...] Read more.
Alzheimer’s disease (AD) remains an incurable neurodegenerative disorder. The concept of theranostics—combining diagnostic and therapeutic functions within a single nanoplatform—has been explored for over a decade. Despite a growing number of publications, no theranostic system has yet reached clinical application for AD. This critical review analyzes the fundamental conceptual contradictions that hinder the clinical translation of theranostic nanoplatforms for AD and identifies alternative strategies where nanotechnology may still be beneficial. The review presents key aspects essential for understanding theranostics challenges: AD molecular targets, analysis of existing nanoplatforms, identification of three inherent conceptual conflicts, and viable alternative approaches. Our analysis reveals three core conceptual conflicts: the pharmacokinetic conflict, where diagnostics demand rapid accumulation and clearance while therapy requires prolonged retention—exacerbated by minimal brain delivery (1–2% ID/g) and peripheral toxicity risks; the dose conflict, characterized by orders-of-magnitude disparities between diagnostic and therapeutic dosing, rarely quantified for identical particles; and the temporal conflict, pitting one-time diagnostics against chronic therapy needs, as long-persisting particles generate irremovable brain background signals. We further identify a pervasive methodological trap: predominant focus on mature β-amyloid (Aβ) fibrils overlooks soluble oligomers as the primary toxic species. We conclude by proposing viable alternatives: preclinical intervention for time-limited “hit-and-clear” applications; coordinated theranostic monitoring with separate diagnostics/therapy; theranostic pairs using ligand-matched, function-optimized particles; and external stimuli for temporal function separation. A practical roadmap guides the transition from conceptual demonstrations to clinical translation. Addressing these contradictions can transform theranostics from elegant chemical constructs into clinically meaningful AD tools. Full article
(This article belongs to the Special Issue From Molecules to Cognition: Biomarkers and Neuropsychological Tools in Neurological Disorders)
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19 pages, 737 KB  
Review
Neurochemical and Energetic Alterations in Depression: A Narrative Review of Potential PET Biomarkers
by Santiago Jose Cornejo Schmiedl, Bryan Astudillo Ortega, Bernardo Sosa-Moscoso, Gabriela González de Armas, Jose Ignacio Montenegro Galarza, Jose A. Rodas and Jose E. Leon-Rojas
Int. J. Mol. Sci. 2026, 27(3), 1267; https://doi.org/10.3390/ijms27031267 - 27 Jan 2026
Viewed by 850
Abstract
Depression is a heterogeneous neuropsychiatric disorder with variable clinical presentation and response to treatment. This variability has motivated interest in neuroimaging biomarkers capable of disease characterization and therapeutic prediction. Positron emission tomography (PET) enables in vivo assessment of cerebral glucose utilization, neurochemical targets, [...] Read more.
Depression is a heterogeneous neuropsychiatric disorder with variable clinical presentation and response to treatment. This variability has motivated interest in neuroimaging biomarkers capable of disease characterization and therapeutic prediction. Positron emission tomography (PET) enables in vivo assessment of cerebral glucose utilization, neurochemical targets, inflammatory markers, and cerebral blood flow. This narrative review synthesizes PET studies conducted predominantly in adults with major depressive disorder diagnosed using DSM-based criteria, with bipolar disorder included only when imaging was performed during a depressive episode. Studies were identified through a structured, non-systematic literature search of major databases. Depression is consistently associated with regionally specific PET alterations within cortico-limbic and cortico-striatal circuits; studies most frequently report reduced glucose-derived PET measures in prefrontal and anterior cingulate regions at baseline, with treatment responders showing relative increases or redistribution of these measures following interventions. Neurochemical PET studies demonstrate altered receptor, transporter, or enzyme-related binding in serotonergic, dopaminergic, and noradrenergic systems, while neuroinflammatory and perfusion studies reveal regionally increased PET signals in subsets of patients. Overall, PET findings indicate convergent, region-specific and neurochemical alterations associated with depressive episodes and treatment response. Interpretation is constrained by methodological and clinical heterogeneity, underscoring the need for harmonized, longitudinal PET studies. Full article
(This article belongs to the Special Issue From Molecules to Cognition: Biomarkers and Neuropsychological Tools in Neurological Disorders)
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