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J Intern Med. 2016 Sep;280(3):300-11. doi: 10.1111/joim.12491. Epub 2016 Apr 1.

Vitamin D insufficiency and cognitive impairment in Asians: a multi-ethnic population-based study and meta-analysis.

Annweiler C1,2, Milea D3,4,5,6, Whitson HE7,8,9, Cheng CY3,4,10,11, Wong TY3,4,10,11, Ikram MK3,12, Lamoureux EL3,4,10,11, Sabanayagam C3,10,11.

Author information

Division of Geriatric Medicine, Department of Neuroscience, Angers University Hospital, University Memory Clinic of Angers, UNAM, University of Angers, Angers, France.
Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Robarts Research Institute, The University of Western Ontario, London, ON, Canada.
Singapore Eye Research Institute, Singapore.
Singapore National Eye Centre, Singapore.
Neuroscience and Behavioural Disorders, Duke-NUS, Singapore.
Division of Ophthalmology, Department of Neuroscience, Angers University Hospital, Angers, France.
Departments of Medicine and Ophthalmology, Duke University Medical School, Durham, NC, USA.
Duke Aging Center, Duke University, Durham, NC, USA.
Durham VA Medical Center, Geriatrics Research Education and Clinical Center, Durham, NC, USA.
Ophthalmology and Visual Sciences Academic Clinical Program, Medical School, Duke-NUS, Singapore.
Department of Ophthalmology, National University of Singapore, Singapore.
Memory Aging & Cognition Centre, National University Health System, Singapore.



The relationship between vitamin D insufficiency and cognitive impairment remains equivocal in Asians. We examined the association between circulating 25-hydroxyvitamin D (25OHD) concentration and cognitive performance in a large multi-ethnic Singaporean population-based study. We also conducted a meta-analysis of 25OHD concentrations amongst cognitively impaired older adults in Asia.


Our population-based cross-sectional study included 2273 persons ≥60 years of age from the Singapore Epidemiology of Eye Diseases (SEED) study (mean ± SD age 70.4 ± 6.2 years; 44.7% female), who were categorized according to 25OHD concentration (i.e. ≤10, 10.1-20 and >20 ng mL(-1) ). The 25OHD concentration was measured and adjusted to reflect a deseasonalized value. Cognition was assessed using the total and domain scores of the Abbreviated Mental Test (AMT). Global cognitive impairment was defined as AMT score of ≤6 if 0-6 years of education and AMT score of ≤8 if >7 years of education. Fully adjusted multivariate models were used. We included seven studies in a meta-analysis of 25OHD and cognition in Asia (6068 participants; 1179 cognitively impaired cases).


Participants with 25OHD levels >20 ng mL(-1) (n = 1302) had higher AMT total scores (mean ± SD 8.5 ± 1.9) and were less likely to have cognitive impairment (14.1%) than participants with lower 25OHD levels (overall P < 0.001, P-trend < 0.001). Deseasonalized 25OHD concentration was associated with AMT score (β = 0.10 per 10 ng mL(-1) , P = 0.035). Vitamin D insufficiency (25OHD ≤20 ng mL(-1) ) was associated with global cognitive impairment (OR 1.56, P = 0.028). Specifically, 25OHD concentration correlated with semantic memory (r = 0.08, P = 0.009) and orientation in time (r = 0.09, P = 0.003). In the meta-analysis, the pooled mean 25OHD difference was -6.83 ng mL(-1) (95% confidence interval -11.36; -2.30), indicating lower 25OHD concentrations amongst cognitively impaired compared to cognitively healthy participants in Asia.


Vitamin D insufficiency is associated with a greater likelihood of and more severe cognitive impairment in Asian populations.


Asia; cognition; older adults; vitamin D

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