Aging generally leads to cognitive decline. As we age, normal processes that help our brains function begin to deteriorate.
For example, one such process is glucose delivery to the brain. Glucose helps provide energy to our brains. As we age, however, our ability to deliver glucose to the brain diminishes. Additionally, aging can lead to decreased activity of an enzyme in the brain called protein phosphatase 2A (PP2A).
Each of these deteriorating processes can lead to an increased amount of tau protein, which are proteins found in the neurons of the central nervous system. Increased amounts of tau protein is called tau hyperphosphorylation.
Tau hyperphosphorylation can lead to dementia, Alzheimer’s disease and other age-related cognitive impairments. This is because tau hyperphosphorylation decreases the amount of tau that would normally bind to what are called microtubules, which in turn increases the amount of free tau proteins, which can accumulate and produce neuronal tangles.
Vitamin D has been shown to play a role in cognition, especially in Alzheimer’s disease. Studies have shown that vitamin D receptors are present in the brain, and that vitamin D can bind to these receptors to help protect the brain. Specifically, vitamin D receptors can act to protect against plaques and tangles that often cause cognitive impairment.
Because hyperphosphorylation of tau proteins can cause tangles in the brain, and vitamin D receptors seem to protect against these tangles, researchers in the present study wondered, is this how vitamin D might work in cognition and Alzheimer’s? Can vitamin D reduce age-related tau hyperphosphorylation and help protect against cognitive decline?
To study this, researchers from Wayne State University examined a group of 40 rats aged 20 months (elderly) and 6 months (young). They grouped these rats by age, and then, within each age group, further assigned them to a vitamin D group or a control group. This equaled 10 rats in each group for each age. The vitamin D group received 42 IU of active vitamin D per kilogram (Kg) of body weight given as an injection.
Two weeks after the rats were given either vitamin D or a saline injection (for the controls), they were tested in a water maze to determine cognitive impairment. They tested both memory and discrimination-learning. The memory test was designed to determine functional problems in the hippocampus. The hippocampus is a major component of the brain and involved in memory.
In this test, the rats were tested 12 times to see how well they could find and swim to a red plastic ball that was randomly placed each time.
The discrimination-learning test was designed to determine functional problems in other areas of the brain. In this test, the rats were tested 8 times to discriminate between black and white visual goals. The black goal was the desired goal and was a ramp to escape the water, while the white goal was the false goal.
After these tests, the researchers studied the brain and hippocampi of the rats. Here is what they found:
- Elderly control rats had lower levels of vitamin D compared to the young control rats, suggesting the elderly rats had an age-related vitamin D deficiency (p<0.05).
- The elderly vitamin D rats showed shorter swim latency in the memory test and more often took the correct path to escape the water compared to the elderly controlled rats (p<0.05).
- Vitamin D supplementation in the elderly aged rats reduced age-related tau hyperphosphorylation at the pre-tangle, intraneuronal tangle, and extracellular tangle sites by 33%, 37%, and 31%, respectively (p<0.05).
- Vitamin D supplementation in the elderly rats increased PP2A activity by 29%, suggesting vitamin D regulates tau hyperphosphorylation by increasing PP2A activity.
- Overall, there were no significant differences between the young control mice and the young mice receiving vitamin D supplementation in any of the analyses.
The researchers concluded,
“In the present study we demonstrate that age-related vitamin D deficiency is associated with tau hyperphosphorylation, decreased brain energy metabolism and PP2A activity, and reduced redox state in the hippocampus and that these neuropathological processes are accompanied by cognitive decline.”
The researchers also noted,
“However, our study is the first to show that providing vitamin D supplementation significantly limited the age-related hyperphosphorylation of tau proteins suggesting a usefulness of this neurohormone in decreasing the risk of neurofibrillary tangle formation.”
This research presents a possible mechanism to how vitamin D may help in age-related cognitive impairment. However, keep in mind, as the researchers note, there is no single therapy to reverse the effects of cognitive decline. More human studies and in the form of randomized controlled trials are needed before we can definitively know if vitamin D helps in cognitive decline and Alzheimer’s.
Briones, T. & Darwish, H. Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state. Neuroscience, 2014.