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Vitamin D3 as a potentially modifiable factor in mild cognitive impairment
  1. Hiroshige Fujishiro
  1. Department of Psychiatry, Kawasaki Memorial Hospital, Kawasaki, Japan
  1. Correspondence to Dr Hiroshige Fujishiro, Department of Psychiatry, Kawasaki Memorial Hospital, Kawasaki, Japan; fujishiro17{at}

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More biomarker-based research is required to determine the effectiveness of interventions in subjects with mild cognitive impairment (MCI)

MCI is a clinical diagnostic term for elderly subjects with impaired cognitive performance that does not significantly interfere with independent living. MCI, an intermediate condition between normal cognition and dementia, is typically divided into amnestic or non-amnestic subtypes, with single-domain or multidomain distinctions. After the diagnosis, some subjects with MCI develop Alzheimer’s disease (AD) dementia or other dementias resulting from non-AD brain diseases, whereas a substantial proportion of subjects may later be diagnosed as cognitively normal or remain diagnosed with MCI even after a prolonged period. Although the reason for the various clinical courses in subjects with MCI remains unclear, a recent large clinicopathological longitudinal study revealed disease heterogeneity underlying MCI.1 Of the 874 subjects diagnosed with MCI, 39.2% died with an MCI diagnosis, 46.8% died with a dementia diagnosis and 13.9% died with a diagnosis of intact cognition during the follow-up period (mean 7.9 years). Over half of the subjects with an MCI diagnosis did not develop dementia. At autopsy, less than one-quarter of MCI subjects showed ‘pure’ AD. Both severe arteriolosclerosis and primary age-related tauopathy pathologies are associated with a clinical MCI diagnosis. These results reveal that MCI is not necessarily a result of the AD pathology. The various neuropathological basis of MCI raises the possibility that clinical trials for MCI may produce conflict results depending on the heterogenous participants.

The MCI practice guideline reported that there are no effective pharmacological treatments for cognitive symptoms in MCI based on the results of previous studies, including the use of vitamin E and vitamin C.2 The committee recommends a possible benefit of two times per week exercise for cognition in MCI, although long-term studies are unavailable. In their JNNP paper Hu et al 3 reports the effects of vitamin D3 supplementation on cognition and blood lipids in 163 subjects with MCI based on a 12-month randomised double-blind placebo-controlled trial. This study revealed that daily oral vitamin D3 supplementation (400 IU/day) for 12 months may improve cognitive function on the Chinese version of the Wechsler Adult Intelligence Scale-Revised and change blood lipid levels in subjects with MCI. Because plasma total cholesterol concentration had an inverse association with Full IQ, the authors hypothesise that the neuroprotective role of vitamin D3 may be associated with reducing total cholesterol. Considering that biomarkers based on neuroimaging and cerebrospinal fluid measures were not used in their study, disease heterogeneity underlying MCI should be postulated. Although vitamin D3 has wide-ranging roles in the regulation of many physiological processes, vitamin D3 supplementation might be effective in the specific MCI subgroup. The previous committee also recommends the inclusion of patient cohorts with specific biomarkers data in treatment studies targeted at specific pathologies such as MCI due to AD for future research.2 Although further studies are needed to determine whether the benefits of vitamin D3 supplementation found in the study by Hu et al could be replicated, biomarker-based research is required for a more precise approach to interventional trials in the appropriate subjects with specific MCI aetiology.4


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  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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