Effect of Memantine Treatment and Combination with Vitamin D Supplementation on Body Composition in the APP/PS1 Mouse Model of Alzheimer's Disease following Chronic Vitamin D Deficiency

Background: Vitamin D deficiency and altered body composition are common in Alzheimer's disease (AD). Memantine with vitamin D supplementation can protect cortical axons against amyloid-ß exposure and glutamate toxicity. Objective: To study the effects of vitamin D deprivation and subsequent treatment with memantine and vitamin D enrichment on whole-body composition using a mouse model of AD. Methods: Male APPswe/PS1dE9 mice were divided into four groups at 2.5 months of age: the control group (n=14) was fed a standard diet throughout; the remaining mice were started on a vitamin D-deficient diet at month 6. The vitamin D-deficient group (n=14) remained on the vitamin D-deficient diet for the rest of the study. Of the remaining two groups, one had memantine (n=14), while the other had both memantine and 10 IU/g vitamin D (n=14), added to their diet at month 9. Serum 25(OH)D levels measured at months 6, 9, 12, and 15 confirmed vitamin D levels were lower in mice on vitamin D-deficient diets and higher in the vitamin D-supplemented mice. Micro-computed tomography was performed at month 15 to determine whole-body composition. Results: In mice deprived of vitamin D, memantine increased bone mineral content (8.7% increase, p<0.01) and absolute skeletal tissue mass (9.3% increase, p<0.05) and volume (9.2% increase, p<0.05) relative to controls. This was not observed when memantine treatment was combined with vitamin D enrichment. Conclusion: Combination treatment of vitamin D and memantine had no negative effects on body composition. Future studies should clarify whether vitamin D status impacts the effects of memantine treatment on bone physiology in people with AD.