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

Abstract

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-β 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.

Effects of memantine and high dose vitamin D on gait in the APP/PS1 mouse model of Alzheimer’s disease following vitamin D deprivation

“…Interestingly, the current study showed that vitamin D deficiency led to an increase in hind stride width, a marker of balance and postural control [3], by month 15 of the study. We have previously shown that vitamin D deficiency does not cause any changes in body composition in APPswe/PS1dE9 mice [24], however it is possible that vitamin D deficiency affected gait through neurological processes. Another study in APPswe/PS1dE9 mice found progressive development of morphological abnormalities in the cerebellar cortex resulting in decreased performance in wirehanging and rotarod tests [22].…”

Effects of risk factors on evoked pain patterns in rat models of experimental knee osteoarthritis

“…A software utility was written to compute the mass of the adipose tissue by multiplying the volume by a predetermined density (0.90 g/cm 3 ). Similarly, skeletal tissue volume was computer using image values of above 190 HU and the mass computer by multiplying the volume with a density of 1.92 g/cm 3 22 …”

Vitamin D supplementation worsens Alzheimer's progression: Animal model and human cohort studies

“…These findings, however, do not preclude the potential clinical benefit of vitamin D supplementation on lower AD risk in younger or middle-aged people before the disease has taken its toll and before AD damage has become irreversible. Supporting this notion, several animal studies have reported that starting vitamin D supplementation at very early stage of disease in AD mice, when amyloid plaques are far from being developed, may benefit AD (Landel, Millet, et al, 2016b;Morello et al, 2018;Wong et al, 2021;Yu et al, 2011). Therefore, timing of supplementation is perhaps an important factor to consider.…”