Pettersen Jacqueline A
Northern Medical Program, University of Northern British Columbia, Prince George, Canada; Division of Neurology, Department of Internal Medicine, University of British Columbia, Vancouver, Canada.
Exp Gerontol. 2017 Apr;90:90-97. doi: 10.1016/j.exger.2017.01.019. Epub 2017 Feb 4.
Insufficiency of 25-hydroxyvitamin D [25(OH)D] has been associated with dementia and cognitive decline. However, the effects of vitamin D supplementation on cognition are unclear. It was hypothesized that high dose vitamin D3 supplementation would result in enhanced cognitive functioning, particularly among adults whose 25(OH)D levels were insufficient (<75nmol/L) at baseline.
Healthy adults (n=82) from northern British Columbia, Canada (54° north latitude) with baseline 25(OH)D levels ≤100nmol/L were randomized and blinded to High Dose (4000IU/d) versus Low Dose (400IU/d) vitamin D3 (cholecalciferol) for 18weeks. Baseline and follow-up serum 25(OH)D and cognitive performance were assessed and the latter consisted of: Symbol Digit Modalities Test, verbal (phonemic) fluency, digit span, and the CANTAB® computerized battery.
There were no significant baseline differences between Low (n=40) and High (n=42) dose groups. Serum 25(OH)D increased significantly more in the High Dose (from 67.2±20 to 130.6±26nmol/L) than the Low Dose group (60.5±22 to 85.9±16nmol/L), p=0.0001. Performance improved in the High Dose group on nonverbal (visual) memory, as assessed by the Pattern Recognition Memory task (PRM), from 84.1±14.9 to 88.3±13.2, p=0.043 (d=0.3) and Paired Associates Learning Task, (PAL) number of stages completed, from 4.86±0.35 to 4.95±0.22, p=0.044 (d=0.5), but not in the Low Dose Group. Mixed effects modeling controlling for age, education, sex and baseline performance revealed that the degree of improvement was comparatively greater in the High Dose Group for these tasks, approaching significance: PRM, p=0.11 (d=0.4), PAL, p=0.058 (d=0.4). Among those who had insufficient 25(OH)D (<75nmol/L) at baseline, the High Dose group (n=23) improved significantly (p=0.005, d=0.7) and to a comparatively greater degree on the PRM (p=0.025, d=0.6).
Nonverbal (visual) memory seems to benefit from higher doses of vitamin D supplementation, particularly among those who are insufficient (<75nmol/L) at baseline, while verbal memory and other cognitive domains do not. These findings are consistent with recent cross-sectional and longitudinal studies, which have demonstrated significant positive associations between 25(OH)D levels and nonverbal, but not verbal, memory. While our findings require confirmation, they suggest that higher 25(OH)D is particularly important for higher level cognitive functioning, specifically nonverbal (visual) memory, which also utilizes executive functioning processes.
25-羟维生素D[25(OH)D]不足与痴呆和认知功能下降有关。然而，补充维生素D对认知的影响尚不清楚。研究假设，高剂量补充维生素D3会改善认知功能，特别是在基线时25(OH)D水平不足(<75nmol/L)的成年人中。
来自加拿大不列颠哥伦比亚省北部（北纬54°）的健康成年人（n=82），其基线25(OH)D水平≤100nmol/L，被随机分为高剂量组（4000IU/天）和低剂量组（400IU/天），并对维生素D3（胆钙化醇）进行为期18周的双盲治疗。评估基线和随访时的血清25(OH)D水平及认知表现，后者包括：符号数字模式测验、言语（音素）流畅性、数字广度以及CANTAB®计算机化测试组。
低剂量组（n=40）和高剂量组（n=42）在基线时无显著差异。高剂量组血清25(OH)D水平显著升高（从67.2±20nmol/L升至130.6±26nmol/L），高于低剂量组（从60.5±22nmol/L升至85.9±16nmol/L），p=0.0001。通过模式识别记忆任务（PRM）评估，高剂量组的非言语（视觉）记忆表现有所改善，从84.1±14.9提高到88.3±13.2，p=0.043（d=0.3）；配对联想学习任务（PAL）完成的阶段数从4.86±0.35增加到4.95±0.22，p=0.044（d=0.5），而低剂量组未出现这种情况。在控制年龄、教育程度、性别和基线表现的混合效应模型中，高剂量组在这些任务上的改善程度相对更大，接近显著水平：PRM，p=0.11（d=0.4），PAL，p=0.058（d=0.4）。在基线时25(OH)D不足(<75nmol/L)的人群中，高剂量组（n=23）有显著改善（p=0.005，d=0.7），且在PRM上的改善程度相对更大（p=0.025，d=0.6）。
非言语（视觉）记忆似乎受益于更高剂量的维生素D补充，特别是在基线时不足(<75nmol/L)的人群中，而言语记忆和其他认知领域则不然。这些发现与最近的横断面和纵向研究一致，这些研究表明25(OH)D水平与非言语记忆而非言语记忆之间存在显著的正相关。虽然我们的发现需要进一步证实，但它们表明较高的25(OH)D对较高水平的认知功能，特别是非言语（视觉）记忆尤为重要，非言语（视觉）记忆也利用执行功能过程。
