The research, made up of human population data and findings from mouse models, concludes that certain biochemical reactions that lead to cognitive impairment and Alzheimer’s disease could begin in the womb – or just after birth – if the foetus or new born do not have sufficient levels of vitamin A.
Writing in the journal Acta Neuropathologica, researchers analysed data from 330 elderly Chinese people, before using studies on genetically engineered mice, to test the associations between vitamin A status and the long-term risk of Alzheimer’s disease.
“Our study showed that marginal vitamin A deficiency (MVAD) is approximately twofold more prevalent than vitamin A deficiency (VAD) in the elderly, and increased cognitive decline is positively correlated with lower vitamin A levels,” wrote the team, led by senior author Professor Weihong Song at the University of British Columbia.
Indeed, the population study showed that 75% of those with either mild or significant vitamin A deficiency had cognitive impairment, compared to 47% of those with normal vitamin A levels.
Further research in mice confirmed this link by showing that even a mild deficiency in vitamin A during pregnancy or just after birth is associated with a long-term increase in the production of amyloid-beta plaques that are associated with Alzheimer’s development.
Furthermore, the team found that when deprived of vitamin A, mice performed worse as adults on a standard test of learning and memory.
Even when mice deprived of vitamin A in the womb were given a normal diet as pups, they performed worse than mice who received a normal amount of the nutrient in the womb but were deprived after birth, revealed the authors.
"Our study clearly shows that marginal deficiency of vitamin A, even as early as in pregnancy, has a detrimental effect on brain development and has long-lasting effect that may facilitate Alzheimer's disease in later life," said Dr Song.
Still, the senior author and his team noted that some reversal is possible; adding that mice deprived of vitamin A in utero but given supplements immediately after birth performed better on the tests than mice that did not receive supplements.
"In some cases, providing supplements to the newborn Alzheimer's disease model mice could reduce the amyloid beta level and improve learning and memory deficits," he said. "It's a matter of the earlier, the better."
Building the evidence
Song and colleagues analysed new data on vitamin A status, cognition, and Alzheimer’s disease from a population of 330 elderly people in Chongqing, China.
Blood levels of vitamin A were measured and classified into vitamin A normal (VAN) if above 1.05 μM, marginal vitamin A deficiency (MVAD) for measures 0.70–1.05 μM, and vitamin A deficient (VAD) for a status of less than 0.70 μM.
“Individuals in VAN, MVAD, and VAD groups accounted for 60.9% (n = 201), 25.8% (n = 85), and 13.3% (n = 44) of total subjects, respectively,” said the team – who noted that there were no significant differences in blood glucose or cholesterol concentrations between the three groups.
However, scores on tests cognitive impairment were significantly higher in both MVAD and VAD groups, said the team.
“When MVAD group and VAD group were combined into a VA insufficiency (VAI) group, lower MMSE scores and higher CDR and ADAS-Cog scores were found in the VAI group compared with those in the VAN group,” they added.
The research team then used a mouse model of Alzheimer’s disease to perform several tests that backed up this observational population data.
Using this mouse model, the team found that both pre- and postnatal MVAD leads to increases in amyloid-beta generation and plaque formation, and that prenatal MVAD worsens the learning and memory deficits already seen in the AD model mice.
Furthermore, supplementation with vitamin A in infancy was found to offset the learning and memory declines seen from prenatal MVAD, said Song and colleagues.
“These results clearly demonstrate that a daily therapeutic dose of vitamin A supplement for 7 days can improve prenatal MVAD-induced learning and memory deficits at different stages of brain development, and the earlier the supplementation the better effect,” said the team.
“Monitoring vitamin A status during pregnancy and infancy and controlling prenatal vitamin A insufficiency may be an effective approach to prevent Alzheimer’s disease development.”
Source: Acta Neuropathologica
Pages 1–16, doi: 10.1007/s00401-017-1669-y
“Marginal vitamin A deficiency facilitates Alzheimer’s pathogenesis”
Authors: Jiaying Zeng, et al