Neurodegenerative diseases, featured by progressive loss of structure or function of neurons, are considered incurable at present. Movement disorders like tremor and postural instability, cognitive or behavioral disorders such as memory impairment are the most common symptoms of them and the growing patient population of neurodegenerative diseases poses a serious threat to public health and a burden on economic development. Hence, it is vital to prevent the occurrence of the diseases and delay their progress. Vitamin D can be transformed into a hormone in vivo with both genomic and non-genomic actions, exerting diverse physiological effects. Cumulative evidence indicates that vitamin D can ameliorate neurodegeneration by regulating pertinent molecules and signaling pathways including maintaining Ca2+ homeostasis, reducing oxidative stress, inhibiting inflammation, suppressing the formation and aggregation of the pathogenic protein, etc. This review updates discoveries of molecular mechanisms underlying biological functions of vitamin D in neurodegenerative diseases including Alzheimer\'s disease, Parkinson\'s disease, multiple sclerosis, and vascular dementia. Clinical trials investigating the influence of vitamin D supplementation in patients with neurodegenerative diseases are also summarized. The synthesized information will probably provoke an enhanced understanding of the neuroprotective roles of vitamin D in the nervous system and provide therapeutic options for patients with neurodegenerative diseases in the future.

Vascular cognitive impairment (VCI), encompassing vascular dementia, has been claimed as the \"second-most common dementia\" after Alzheimer Disease. Whether or not this is true, the clinical picture of most dementia in older people includes vascular disease. There are no validated pharmacological targets for prevention or treatment of VCI. This has inspired a multitude of potential treatment approaches, reflected by the articles in this Special Issue. These include in vitro testing of the novel oral anticoagulant dabigatran for protection against β-amyloid neurotoxicity, and an overview of neuroinflammation in VCI and the role of circulating markers (PIGF, VEGF-D) identified by the MarkVCID study. There are reviews of potential therapeutics, including adrenomedullin and nootropic preparations (exemplified by cerebrolysin). The role of sleep is reviewed, with possible therapeutic targets (5HT2A receptors). There is a clinical study protocol (INVESTIGATE-SVD) and a feasibility analysis for a secondary prevention trial in small vessel disease. Clinical data include secondary analyses of blood pressure and cerebral blood flow from a longitudinal clinical trial (NILVAD), differences between methylphenidate and galantamine responders and non-responders (STREAM-VCI), appraisal of treatment approaches in India, and primary outcomes from a randomised trial of Argentine tango dancing to preserve cognition in African American women (ACT). Treating vascular disease has great potential to improve global cognitive health, with public health impacts alongside individual benefit. Vascular disease burden varies across populations, offering the possibility of proactively addressing health inequity in dementia using vascular interventions. The next 5-10 years will witness cost-effective lifestyle interventions, repurposed drugs and novel therapeutics.

BACKGROUND: Staging vascular cognitive impairment (VCI) might be useful for sample selection in clinical trials and for guiding clinical decision-making. Clinical dementia rating (CDR) has been applied for staging cognitive impairments of different etiologies, but it may underestimate severity of non-Alzheimer\'s disease cognitive deficits.
METHODS: Out of a total of 147 elderly subjects, 23 (mean age: 72.95 ± 7.51 years; 56% female; mean schooling: 9.52 ± 5.11 years) fulfilled clinical and neuroimaging criteria for VCI. Correlations among cognitive and functional status and scores in CDR and its subsums (CDR Sum of Boxes - CDR-SoB - and CDR Functional Subsum - CDR-FUNC) were performed.
RESULTS: Both CDR-SoB and CDR-FUNC correlated with global cognitive performance, functional status, CLOX 2, working memory and abstraction tests. CDR global score only correlated with functional status.
CONCLUSIONS: CDR-FUNC, as well as CDR-SoB, appear to be better indexes of severity in VCI than CDR global score.