Cognitive impairmentVitamin D levels

Investigation of cognitive impairment with respect to serum 25(OH)D levels has been an active field of research, with the first reports appearing in the journal literature in 200612

By mid-2009, a systematic review found only four papers reporting a significant positive correlation between serum 25(OH)D and cognitive function3. However, there have been a number of positive correlations reported since then, summarized here in chronological order.

In a cross-sectional study of 60 older adults (30 African Americans and 30 European Americans), vitamin D status, cognitive performance, physical performance, and bone mineral density (BMD) were assessed. Differences between groups and differences between those with vitamin D deficiency and those with normal vitamin D levels were tested. African Americans had a lower mean 25-hydroxyvitamin D level (18.0 ng/ml; SD, 6.9) compared to European Americans (25.2 ng/ml; SD, 7.0; p < 0.0001). Participants with vitamin D deficiency performed worse on a measure of cognitive performance, the Short Blessed Test (10.87 vs 6.31; p = .016); the Physical Performance Test (PPT) (27.0 vs 29.0; p = 0.04); and had lower BMD (0.82 vs 0.91; p = 0.005) and t scores (-1.29 vs -0.72; p = 0.008) of the hip4.

This population-based cross-sectional study included 3,369 men aged 40-79 years from eight centres enrolled in the European Male Ageing Study. Cognitive function was assessed using the Rey-Osterrieth Complex Figure (ROCF) test, the Camden Topographical Recognition Memory (CTRM) test and the Digit Symbol Substitution Test (DSST). In age-adjusted linear regressions, high levels of 25(OH)D were associated with high scores on the copy component of the ROCF test (beta per 10 nmol/l = 0.096; 95% CI 0.049 to 0.144), the CTRM test (beta per 10 nmol/l = 0.08; 95% CI 0.03 to 0.12) and the DSST (beta per 10 nmol/l = 0.32; 95% CI 0.24 to 0.40). After adjusting for additional confounders, 25(OH)D levels were associated with only score on the DSST (beta per 10 nmol/l = 0.15; 95% CI 0.05 to 0.25). Locally weighted and spline regressions suggested the relationship between 25(OH)D concentration and cognitive function was most pronounced at 25(OH)D concentrations below 35 nmol/l5.

A cross-sectional investigation of 25(OH)D and cognition was completed in 377 black and 703 non-black (mainly Caucasian) elders (65-99 years) participating in the nutrition and memory in elders study. Participants underwent a comprehensive neuropsychological battery, and 25(OH)D concentrations were obtained.  After adjusting for age, sex, race, body mass index, education, center, kidney function, seasonality, physical activity, and alcohol use, 25(OH)D was associated with better performance on the following cognitive tests:  trails A (beta = -0.49, p < 0.03), trails B (beta = -0.73, p < 0.02), digit symbol (beta = 0.19, p < .001), matrix reasoning (beta = 0.04, p < 0.02), and block design (beta = 0.07, p < 0.04) tests. Associations remained after adjustment for homocysteine, apolipoprotein E epsilon4 (apoE4) allele, plasma B vitamins, and multivitamin use (y/n). 25(OH)D concentrations >20 ng/mL were associated with better performance on tests of executive function, including trails A (80.5 vs 95, p < 0.05), trails B (205s vs 226s, p < 0.05), matrix reasoning (7.8 vs 7.0, p = 0.03), and digit symbol (31.5 vs 37, p < 0.01). There were no associations between 25(OH)D and memory tests. Factor analysis yielded factors for memory, executive function, and attention/processing speed. After adjustment, 25(OH)D was associated with the executive function (beta = 0.01, p < 0.01) and attention/processing speed factors (beta = 0.01, p = .03), but not the memory factor (beta = -0.001, p = 0.65)6.

Participants were 1766 adults aged 65 years and older from the Health Survey for England 2000, a nationally representative population-based study. Cognitive impairment was assessed using the Abbreviated Mental Test Score. The cross-sectional relation of serum 25(OH)D quartiles to cognitive impairment was modeled using logistic regression. In all, 212 participants (12%) were cognitively impaired. Odds ratios (95% confidence intervals) for cognitive impairment in the first (8-30 nmol/L), second (31-44 nmol/L), and third (45-65 nmol/L) quartiles of serum 25(OH)D compared with the fourth (66-170 nmol/L) were 2.3 (1.4-3.8), 1.4 (0.8-2.4), and 1.1 (0.6-1.9), after adjustment for age, sex, education, ethnicity, season of testing, and additional risk factors for cognitive impairment (P for linear trend = 0.001)7.

Slinin et al8 measured 25(OH)D and assessed cognitive function using the Modified Mini-Mental State Examination (3MS) and Trail Making Test Part B (Trails B) in a cohort of 1,604 men enrolled in the Osteoporotic Fractures in Men Study and followed them for an average of 4.6 years for changes in cognitive function. In a model adjusted for age, season, and site, men with lower 25(OH)D levels seemed to have a higher odds of cognitive impairment, but the test for trend did not reach significance (impairment by 3MS: odds ratio [OR] 1.84, 95% CI, 0.81-4.19 for quartile [Q] 1; 1.41, 0.61-3.28 for Q2; and 1.18, 0.50-2.81 for Q3, compared with Q4 [referent group; p trend = 0.12]; and impairment by Trails B: OR 1.66, 95% CI 0.98-2.82 for Q1; 0.96, 0.54-1.69 for Q2; and 1.30, 0.76-2.22 for Q3, compared with Q4 [p trend = 0.12]). Adjustment for age and education further attenuated the relationships. There was a trend for an independent association between lower 25(OH)D levels and odds of cognitive decline by 3MS performance (multivariable OR 1.41, 95% CI 0.89-2.23 for Q1; 1.28, 0.84-1.95 for Q2; and 1.06, 0.70-1.62 for Q3, compared with Q4 [p = 0.10]), but no association with cognitive decline by Trails B.

The subjects, 752 women aged > or =75 years from the Epidémiologie de l’Ostéoporose (EPIDOS) cohort in France, were divided into 2 groups according to serum 25(OH)D concentrations (either deficient, <10 ng/mL, or nondeficient, > or =10 ng/mL). Cognitive impairment was defined as a Pfeiffer Short Portable Mental State Questionnaire (SPMSQ) score <8. Age, body mass index, number of chronic diseases, hypertension, depression, use of psychoactive drugs, education level, regular physical activity, and serum intact parathyroid hormone and calcium were used as potential confounders. Compared with women with serum 25(OH)D concentrations > or =10 ng/mL (n = 623), the women with 25(OH)D deficiency (n = 129) had a lower mean SPMSQ score (p < 0.001) and more often had an SPMSQ score <8 (p = 0.006). There was no significant linear association between serum 25(OH)D concentration and SPMSQ score (beta = -0.003, 95% CI, -0.012 to 0.006, p = 0.512). However, serum 25(OH)D deficiency was associated with cognitive impairment (crude odds ratio [OR] = 2.08 with p = 0.007; adjusted OR = 1.99 with p = 0.017 for full model; and adjusted OR = 2.03 with p = 0.012 for stepwise backward model)9.

Llewellyn et al10 determined whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population-based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests A and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing. The multivariate adjusted relative risk (95% CI of substantial cognitive decline on the MMSE in participants who were severely serum 25(OH)D deficient (levels <25 nmol/L) in comparison with those with sufficient levels of 25(OH)D (>/=75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH)D deficient compared with those with sufficient levels of 25(OH)D. No significant association was observed for Trail-Making Test A.

Thus, at the time of this review (August, 2010), we found ten journal papers reporting a direct correlation between serum 25(OH)D level and cognitive function, or, alternatively, an inverse correlation between serum 25(OH)D level and cognitive impairment.

Page last edited: 09 May 2011

References

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