Cognitive impairment (CI) is a frequent complication affecting people with multiple sclerosis (MS). The causes of CI in MS are not fully understood. Besides MRI measures, few other biomarkers exist to help us predict the development of CI and understand its biology. MicroRNAs (miRs) are relatively stable, non-coding RNA molecules about 22 nucleotides in length that can serve as biomarkers and possible therapeutic targets in several autoimmune and neurodegenerative diseases, including the dementias. In this review, we identify dysregulated miRs in MS that overlap with dysregulated miRs in cognitive disorders and dementia and explore how these overlapping miRs play a role in CI in MS. are known to contribute to various forms of dementia and show abnormal expression in MS. These overlapping miRs are involved in pathways related to apoptosis, neuroinflammation, glutamate toxicity, astrocyte activation, microglial burst activity, synaptic dysfunction, and remyelination. The mechanisms of action suggest that these miRs may be related to CI in MS.From our review, we also delineated miRs that could be neuroprotective in MS, namely miR-23a, miR-219, miR-214, and miR-22.Further studies can help clarify if these miRs are responsible for CI in MS, leading to potential therapeutic targets.

Purpose of reviewPure autonomic failure (PAF) is a peripheral autonomic neurodegenerative disease caused by alpha-synuclein deposition that is predominantly confined to peripheral autonomic neurons. Patients present with insidious features of autonomic failure that have a chronic course.In this review, we highlight the features of PAF, the differentiating features from other autonomic neuropathies, the diagnostic tests, and the predictors for conversion to a central synucleinopathy.Recent findingsNatural history studies have defined the predictors for and rate of conversion to a central alpha-synucleinopathy. Skin immunohistochemistry techniques and demonstration of length-dependent neuronal loss of both somatic and autonomic small fiber nerves, and intraneural phosphorylated synuclein deposition provide diagnostic biomarkers. In the future, diagnosis maybe supported by measuring cerebrospinal fluid alpha-synuclein oligomers using techniques, such as protein misfolding cyclic amplification assay and real-time quaking-induced conversion.SummaryPAF is a sporadic peripheral autonomic neurodegenerative disease that belongs to the group of disorders known as alpha-synucleinopathies. Peripheral autonomic manifestations are similar to those seen in other autonomic neuropathies, particularly, diabetic autonomic neuropathy, amyloid polyneuropathy, and autoimmune autonomic neuropathies. Novel diagnostic procedures like skin immunohistochemistry for alpha-synuclein, and protein amplification techniques are being investigated to provide an earlier and more specific diagnosis. A substantial number of PAF patients’ phenoconvert to a central alpha-synucleinopathy.

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