Dementia 1.7X higher risk if diabetic and low vitamin D - Jan 2022

Association of serum 25-hydroxyvitamin D concentrations with risk of dementia among individuals with type 2 diabetes: A cohort study in the UK Biobank

PLoS Med 19(1): e1003906. https://doi.org/10.1371/iournal.pmed.1003906
Tingting Gengg1,2, Qi Lug1, Zhenzhen Wanp?1, Jingyu Guo1, Liegang Liu liugang026 at hust.edu.cn 1, An Pan2, Gang Lmg1*
1 Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 2 Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Background
Several epidemiological studies have suggested that vitamin D status is associated with risk of dementia in general populations. However, due to the synergistic effect between diabetic pathology and neuroinflammation, and the prothrombotic profile in patients with diabetes, whether vitamin D is associated with risk of dementia among patients with diabetes is unclear. This study aimed to investigate the associations of circulating vitamin D levels with risks of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VD) among adults with type 2 diabetes (T2D).

Methods and findings
This study included 13,486 individuals (>60 years) with T2D and free of dementia at recruitment (2006-2010) from the UK Biobank study. Serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured using the chemiluminescent immunoassay method at recruitment. Serum 25(OH)D > 75 nmol/L was considered sufficient, according to the Endocrine Society Clinical Practice Guidelines. Incidence of all-cause dementia, AD, and VD cases was ascertained using electronic health records (EHRs). Each participant’s person- years at risk were calculated from the date of recruitment to the date that dementia was reported, date of death, date of loss to follow-up, or 28 February 2018, whichever occurred first. Among the 13,486 individuals with T2D (mean age, 64.6 years; men, 64.3%), 38.3% had vitamin D > 50 nmol/L and only 9.1% had vitamin D > 75 nmol/L.
During a mean followup of 8.5 years, we observed 283 cases of all-cause dementia, including 101 AD and 97 VD cases. Restricted cubic spline analysis demonstrated a nonlinear relationship between serum 25(OH)D and risk of all-cause dementia (Pnonlinearity < 0.001) and VD (Pnonlinearity = 0.007), and the nonlinear association reached borderline significance for AD (Pnonlinearity = 0.06), with a threshold at around a serum 25(OH)D value of 50 nmol/L for all the outcomes.
Higher serum levels of 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD.

The multivariate hazard ratios and 95% confidence intervals for participants who had serum 25(OH)D > 50 nmol/L, compared with those who were severely deficient (25[OH]D < 25 nmol/L), were 0.41 (0.29-0.60) for all-cause dementia (Ptrend < 0.001), 0.50 (0.27-0.92) for AD (Ptrend = 0.06), and 0.41 (0.22-0.77) for VD (Ptrend = 0.01). The main limitation of the current analysis was the potential underreporting of dementia cases, as the cases were identified via EHRs.

Conclusions
In this study, we observed that higher concentrations of serum 25(OH)D were significantly associated with a lower risk of all-cause dementia, AD, and VD among individuals with T2D. Our findings, if confirmed by replication, may have relevance for dementia prevention strategies that target improving or maintaining serum vitamin D concentrations among patients with T2D.
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Author summary

Why was this study done?
Compared with the general populations, individuals with diabetes are particularly susceptible to both vitamin D deficiency and increased risk of developing dementia.
Although some epidemiological studies have linked lower vitamin D concentrations with risk of dementia in general populations, the evidence regarding the relationship between vitamin D status and dementia risk among patients with diabetes is scarce.
What did the researchers do and find?
We conducted an analysis using data from the UK Biobank study to examine the association of serum vitamin D levels with risk of dementia among 13,486 patients with type 2 diabetes who were >60 years old.
Higher serum levels of vitamin D were significantly associated with a lower risk of dementia.
What do these findings mean?
We observed that vitamin D status may be associated with risk of all-cause dementia, vascular dementia, and Alzheimer disease, and this is important as our data suggest that vitamin D deficiency (serum 25OHD < 50 nmol/L) is common in individuals with diabetes.
The findings suggest the possibility that serum vitamin D screening among patients with diabetes may be useful in dementia care and prevention.

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