Defining the underlying pathology of corticobasal syndrome using clinical features and biomarkers.

Prognostic factors of survival in corticobasal syndrome and corticobasal degeneration: A scoping review

From clinical phenotypes to molecular precision: multimodal biomarkers for progressive supranuclear palsy

It is concluded that the shift from clinical-only diagnostic criteria to a biomarker-enabled molecular framework is the necessary catalyst for developing effective disease-modifying therapies for PSP and related 4R-tauopathies.

FRONTOTEMPORAL DEMENTIA - COMPREHENSIVE INSIGHTS INTO PATHOGENESIS, DIAGNOSIS, AND INNOVATIVE TREATMENTS

Frontotemporal dementia (FTD) is a clinically and genetically diverse group of neurodegenerative disorders predominantly affecting the frontal and anterior temporal lobes, leading to progressive changes in behavior, language, and executive function. FTD is the most common cause of young-onset dementia and third overall among degenerative dementias, with a prevalence of 15–22 per 100,000 and an incidence of 2.7–4.1 per 100,000. The core clinical syndromes include the behavioral variant (bvFTD), semantic and nonfluent primary progressive aphasias (svPPA, nfvPPA), and overlap with motor disorders such as progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Genetic mutations, especially C9orf72, GRN, and MAPT, are responsible for most familial cases and involve proteinopathies with TDP-43, tau, and FUS proteins. Biomarkers (e.g., neurofilament light chain, progranulin) and neuroimaging are used to improve detection and differentiate subtypes, although reliable biomarkers are lacking. Management is largely supportive, with a combination of non-pharmacological therapies (e.g., exercise, speech and occupational strategies, behavioral tactics, caregiver education) and pharmacotherapy for neuropsychiatric symptoms. Clinical trials explore gene therapies and disease-modifying drugs, indicating a move towards personalized medicine. Despite major advances, obstacles persist for early detection and effective therapies, underlining the need for sustained multidisciplinary research in FTD. 

Cognitive profiles in idiopathic normal pressure hydrocephalus and Alzheimer's disease

Background Idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) are neurodegenerative disorders with partly overlapping clinical features. Since the treatment is different, we need better knowledge about how the cognitive profile differs between these conditions. Objective We aimed to compare the cognitive profile of iNPH patients with that of a large cohort of confirmed AD patients. Methods Patients diagnosed with iNPH and accepted for shunt surgery were compared with patients with biomarker verified Alzheimer's disease in The Norwegian Register of Persons Assessed for Cognitive symptoms (NorCog). All patients underwent a standardized cognitive assessment with age and education adjusted z-scores. We used the Clinical Dementia Rating Scale (CDR) to adjust for disease severity. Since the cognitive score distributions were highly skewed, we used nonparametric analyses stratified by CDR stage combined with multinomial logistic regression. Results In total, 276 iNPH patients were compared to 1113 AD patients. iNPH patients performed significantly poorer on phonemic fluency [median z-score difference (AD—iNPH) 0.30, 95% confidence interval (CI) 0.20 to 0.50], but significantly better on other cognitive tests, in particular immediate (median difference −0.35, 95% CI −0.49 to −0.20) and delayed recall (median difference −0.46, 95% CI −0.59 to −0.34). The differences persisted after adjustment for CDR and were most pronounced in early stages of the disease. Conclusions iNPH seems to affect phonemic fluency more and memory less than AD. As the disease progresses, the cognitive profiles become more similar, and the conditions cannot be distinguished by cognitive tests.

Clinical and Genetic Spectrum of ATP1A3-Related Disorders

The results highlight the need for a unified diagnostic framework for ATP1A3-related disorders and demonstrate the feasibility and scientific value of coordinated rare disease research in resource-limited settings.

A review of Limbic-predominant age-related TDP-43 encephalopathy (LATE)

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently recognized neurodegenerative dementia in the most elderly individuals, characterized by accumulation of TDP-43 protein aggregates in limbic and medial temporal lobe structures. This is clinically important pathology as it often mimics Alzheimer’s disease (AD) and is now understood to be a common contributor to cognitive decline in the “oldest-old”. Pathologically, LATE is distinguished from AD by TDP-43-positive neuronal inclusions (rather than amyloid plaques and neurofibrillary tangles), typically affecting the amygdala, hippocampus, and other limbic regions, often accompanied by hippocampal sclerosis. Clinically, LATE presents with a gradually progressive amnestic dementia syndrome similar to AD which complicates diagnosis. Currently, there are no established antemortem biomarkers for LATE, and definitive diagnosis relies on postmortem confirmation. However, an AD-like dementia with negative amyloid and tau biomarkers in a patient of advanced age is suggestive of LATE. No disease-modifying treatment exists at this time, however multiple therapeutic strategies are under investigation, including immunotherapies targeting pathological TDP-43, small molecules that enhance TDP-43 clearance, and gene or antisense approaches to mitigate TDP-43 toxicity. Continued research is critical to develop effective biomarkers and therapies for this prevalent but under-recognized TDP-43 proteinopathy.