Low Vitamin D and Its Association with Cognitive Impairment and Dementia

Table 1

Summary of cross-sectional and longitudinal studies depicting association between serum 25(OH)D, cognitive impairment, and Alzheimer’s disease and other dementia.

Study	Study design	Sample size	Study period	Population	Cognitive test	Vitamin D levels	Outcomes
Schneider et al. [25]	Longitudinal study	13,044	20 years	Mean age 57 years; From USA	DWRT; DSST, WFT	Insufficiency; 20–30 ng/ml; Sufficiency > 30 ng/ml; Deficiency < 20 ng/ml	Multivariate-adjusted linear mixed effect model used for analysis.; No significant association with cognitive decline deficient versus sufficient: –0.035 (95% CI – 0.104 to 0.033) and intermediate versus sufficient: –0.029 (95% CI – 0.080 to 0.023)).
Olsson et al. [22]	Longitudinal study	2,841	18 years	Mean age 68 years; From Sweden	MMSE	Deficient < 50 nmol/L; Sufficient > 75 nmol/L	Cox proportional hazards regression (95% CI: 0.59, 1.31) in men with plasma 25(OH)D concentrations 50 compared with 0.75 n·mol/L. (95% CI: 0.63, 1.32) for the lowest compared with highest tertiles of vitamin D intake.
Feart et al. [21]	Longitudinal study	916	12 years	Mean age 65 years and more; From France	MMSE; Benton visual retention test; Trail making test	Sufficient > 50 nmol/L; Insufficient 25–50 nmol/L; Deficiency < 25 nmol/L	Multivariate analysis Vitamin D deficiency and insuffiency had double the risk of all cause dementia with 95% CI (1.21–3.71) for deficiency and 95% CI (1.17–3.36) for insufficiency
Beydoun et al. [26]	Longitudinal study	1,803	10 years	Age (30–64 years); From USA; White urban adults; African-Americans	MMSE; CVLT; TMT-B; BVRT; CDT; DF-S and DFS-B; AF		Linear regression; Higher aseline serum 25OHD was linked toa slower decline in verbal fluency (); Higher intake of vitamin D was associated with aslower rate of decline constructive ability ().; Use of vitamin D supplements during follow-up was related to slower rate of decline in verbal fluency among older individuals.
Goodwill et al. [27]	Longitudinal study	252	10 years	Age (55–67 years); From Australia	CVLT-11; TMT-B; CERAD,	Deficient < 25 nmol/L	One-way ANOVA and Pearson Chi square Vitamin D > 25n·mol/L performed better on verbal fluency (95% CI = 0.53, 4.40) and TMT-B time (95% CI = −32.86, −3.61), with higher executive function (95% CI: 0.44,2.37); These relationships persisted 10 years later in the follow-up
Laughlin et al. [9]	Longitudinal study	1,058	12 years	MMSE; TMT; Halstead–Reitan neuropsychological test; Animal naming category test, fluency test	MMSE; TMT; Halstead–Reitan neuropsychological test; Animal naming category test, fluency test	Insufficiency ˂ 30 ng/ml	Linear mixed effect regression model. Vitamin D insufficiency associated with poor performance on MMSE(). No association found on follow-up
Jorde et al. [23]	Longitudinal study	4,624	13 years	Age 54.9 years; From Norway	MMSE	Continuous variable	Linear regression; Association of low vitamin D and CI found in older, more than 65 years () at cross-sectional level; no association found on follow-up
Moon et al. [24]	Longitudinal study	412	5 years	Mean age 74; From Korea	MMSE	Deficiency 25–49 nmol/L; Severe deficiency ˂ 25nmol/L; Sufficiency ˃ 50 nmol/L	One-way ANOVA; Severe Vitamin D deficiency was associated with future risk of MCI and dementia. 95% CI (1.46–14.8)
Lam et al. [28]	Longitudinal study	179	—	Mean age 74; From Korea	MMSE and RAVLT	31-334.4 mol/L (mean 84.7 nmol/L)	Bayesian mixed model; 25(OH)D levels were negatively associated

MSE: Mini-Mental Status Examination, WFT: word fluency test, DSST: digit symbol substitution test, DWRT: delayed word recall test, and TMT: trial making test; MCI: mild cognitive impairment and RAVLT: Rey auditory verbal learning test; Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), California Verbal Learning Test Second Edition (CVLT-II), verbal fluency and trail making test-B (TMT-B), delayed free recall (DFR), digit span forward and backward tests (DS-F and DS-B), Benton Visual Retention Test (BVRT), animal fluency test (AF), Brief Test of Attention (BTA), and Clock Drawing Test (CDT).