The effects of Vitamin D Insufficiency and Seasonal Decrease on cognition.

BACKGROUND: Vitamin D3 (cholecalciferol) deficiency has been associated with dementia and cognitive decline. Which cognitive domains are most associated with D3 levels and how seasonal fluctuations in levels relate to cognition is unclear. We addressed these questions using a prospective observational study examining associations between D3 levels and cognition among individuals living in northern latitudes (54°N) in summer and winter. METHODS: Healthy adult participants underwent testing in summer and winter of D3 levels and cognition, using the Symbol digit Modalities test, phonemic fluency, digit Span and CANTAB battery. RESULTS: Of 32 participants tested in the summer, 46% were D3 insufficient (<75 nmol/L) and performed worse on digit Span Backward (DS-B) (µ=5.8, SD=2) than those who were sufficient (µ=7.9, SD=2), p=0.018. In multivariate analyses, sufficiency status was an independent predictor of dS-B, (b=0.41, p=0.02). The majority (63%) of 19 participants tested in winter were D3 insufficient, with levels declining by a median of 15 nmol/L overall. Those with insufficient levels performed worse (i.e., higher scores) on the CANTAB Spatial Working Memory (SWM) task (µ=36.1, SD=6 versus µ=29.3, SD=8), p=0.05). Those with larger drops in levels (≥15 nmol/L) showed decline/less improvement on the CANTAB one touch Stockings of Cambridge (OTS) task, (µ=0.50, SD=1.9 versus µ=-2.11, SD=2.6, p=0.01), a test of working memory/executive functioning. CONCLUSIONS: Vitamin D3 insufficiency and seasonal declines ≥15 nmol/L were associated with inferior working memory/executive functioning. While our findings require confirmation, they suggest that sufficient D3 levels should be maintained year-round, likely necessitating supplementation, at least during winter at higher latitudes.

Syntaxin 1A is required for normal in utero development.

We have generated a syntaxin 1A knockout mouse by deletion of exons 3 through 6 and a concomitant insertion of a stop codon in exon 2. Heterozygous knockout animals were viable with no apparent phenotype. In contrast, the vast majority of homozygous animals died in utero, with embryos examined at day E15 showing a drastic reduction in body size and development when compared to WT and heterozygous littermates. Surprisingly, out of a total of 204 offspring from heterozygous breeding pairs only four homozygous animals were born alive and viable. These animals exhibited reduced body weight, but showed only mild behavioral deficiencies. Taken together, our data indicate that syntaxin 1A is an important regulator of normal in utero development, but may not be essential for normal brain function later in life.