Vitamin D (VitD) deficiency can exacerbate AD progression and may cause changes in brain metabolite levels that can be detected by magnetic resonance spectroscopy (MRS). The purpose of this study was to determine whether chronic VitD deficiency in an AD mouse model caused persistent metabolite levels changes in the hippocampus associated with memory performance. Six-month-old APPSwe/PS1ΔE9 (APP/PS1) mice (N = 14 mice/group) were fed either a VitD deficient (VitD-) diet or a control diet. Metabolite level changes in the hippocampus were evaluated by 1H MRS using a 9.4 T MRI. Ventricle volume was assessed by imaging and spatial memory was evaluated using the Barnes maze. All measurements were made at 6, 9, 12, and 15 months of age. At 15 months of age, amyloid plaque load and astrocyte number were evaluated histologically (N = 4 mice/group). Levels of N-acetyl aspartate and creatine were lower in VitD- mice compared to control diet mice at 12 months of age. VitD deficiency did not change ventricle volume. Lactate levels increased over time in VitD- mice and increases from 12 to 15 months were negatively correlated with changes in primary latency to the target hole in the Barnes Maze. VitD- mice showed improved spatial memory performance compared to control diet mice. VitD- mice also had more astrocytes in the cortex and hippocampus at 15 months than control diet mice. This study suggests that severe VitD deficiency in APP/PS1 mice may lead to compensatory changes in metabolite and astrocyte levels that contribute to improved performance on spatial memory tasks.

Significance Statement: Hemodialysis (HD) results in reduced brain blood flow, and HD-related circulatory stress and regional ischemia are associated with brain injury over time. However, studies to date have not provided definitive direct evidence of acute brain injury during a HD treatment session. Using intradialytic magnetic resonance imaging (MRI) and spectroscopy to examine HD‐associated changes in brain structure and neurochemistry, the authors found that multiple white (WM) tracts had diffusion imaging changes characteristic of cytotoxic edema, a consequence of ischemic insult and a precursor to fixed structural WM injury. Spectroscopy showed decreases in prefrontal N-acetyl aspartate (NAA) and choline concentrations consistent with energy deficit and perfusion anomaly. This suggests that one HD session can cause brain injury and that studies of interventions that mitigate this treatment's effects on the brain are warranted.

Background: Hemodialysis (HD) treatment-related hemodynamic stress results in recurrent ischemic injury to organs such as the heart and brain. Short-term reduction in brain blood flow and long-term white matter changes have been reported, but the basis of HD-induced brain injury is neither well-recognized nor understood, although progressive cognitive impairment is common.

Methods: We used neurocognitive assessments, intradialytic anatomical magnetic resonance imaging, diffusion tensor imaging, and proton magnetic resonance spectroscopy to examine the nature of acute HD-associated brain injury and associated changes in brain structure and neurochemistry relevant to ischemia. Data acquired before HD and during the last 60 minutes of HD (during maximal circulatory stress) were analyzed to assess the acute effects of HD on the brain.

Results: We studied 17 patients (mean age 63±13 years; 58.8% were male, 76.5% were White, 17.6% were Black, and 5.9% were of Indigenous ethnicity). We found intradialytic changes, including the development of multiple regions of white matter exhibiting increased fractional anisotropy with associated decreases in mean diffusivity and radial diffusivity—characteristic features of cytotoxic edema (with increase in global brain volumes). We also observed decreases in proton magnetic resonance spectroscopy–measured N-acetyl aspartate and choline concentrations during HD, indicative of regional ischemia.

Conclusions: This study demonstrates for the first time that significant intradialytic changes in brain tissue volume, diffusion metrics, and brain metabolite concentrations consistent with ischemic injury occur in a single dialysis session. These findings raise the possibility that HD might have long-term neurological consequences. Further study is needed to establish an association between intradialytic magnetic resonance imaging findings of brain injury and cognitive impairment and to understand the chronic effects of HD-induced brain injury.