The Moderating Effect of Serum Vitamin D on the Relationship between Beta-amyloid Deposition and Neurodegeneration

Abstract

Objective: Previous studies have reported that vitamin D deficiency increased the risk of Alzheimer's disease (AD) dementia in older adults. However, little is known about how vitamin D is involved in the pathophysiology of AD. Thus, this study aimed to examine the association and interaction of serum vitamin D levels with in vivo AD pathologies including cerebral beta-amyloid (Aβ) deposition and neurodegeneration in nondemented older adults.

Methods: 428 Nondemented older adults were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a prospective cohort that began in 2014. All participants underwent comprehensive clinical assessments, measurement of serum 25-hydroxyvitamin D (25[OH]D), and multimodal brain imaging including Pittsburgh compound B (PiB) positron emission tomography and magnetic resonance imaging. Global PiB deposition was measured for the Aβ biomarker. Intracranial volume-adjusted hippocampal volume (HVa) was used as a neurodegeneration biomarker.

Results: Overall, serum 25(OH)D level was not associated with either Aβ deposition or HVa after controlling for age, sex, apolipoprotein E ε4 positivity, and vascular risk factors. However, serum 25(OH)D level had a significant moderating effect on the association between Aβ and neurodegeneration, with lower serum 25(OH)D level significantly exacerbating cerebral Aβ-associated hippocampal volume loss (B = 34.612, p = 0.008).

Conclusion: Our findings indicate that lower serum vitamin D levels may contribute to AD by exacerbating Aβ-associated neurodegeneration in nondemented older adults. Further studies to explore the potential therapeutic effect of vitamin D supplementation on the progression of AD pathology will be necessary.

Keywords: Alzheimer disease; Biomarkers; Neuroimaging; Vitamin D.

Fig. 1

The moderation analysis of serum 25(OH)D level on the relationship between global Aβ deposition and HVa. Age, sex, APOE4 positivity, and vascular risk factor score were adjusted in this model. 25(OH)D, 25-hydroxyvitamin D; Aβ, beta-amyloid; HVa, adjusted hippocampal volume; APOE4, apolipoprotein ɛ4.

Fig. 2

Association between global Aβ deposition and HVa in lower (serum 25[OH]D < 16.09 ng/ml) and upper (serum 25[OH]D > 24.30 ng/ml) tertile groups of serum 25(OH)D levels, respectively. Predicted HVa, corresponding to an individual’s global Aβ deposition after adjustment for covariates including age, sex, APOE4 carrier status, and vascular risk factor score, is presented. Blue/red dots indicate individuals in the lower (1st) and upper (3rd) tertile group of serum 25(OH)D level, respectively. Solid lines represent the regression lines. Gray dashed line demonstrates the regression line for whole participants. 25(OH)D, 25-hydroxyvitamin D; Aβ, beta-amyloid; HVa, adjusted hippocampal volume; APOE4, apolipoprotein ɛ4; SUVR, standardized uptake value ratio.