Diet and antioxidant hypotheses for neurodegeneration

a. Vitamin E complex. We are examining various nutrients in relation to age-related cognitive impairment and AD. In collaboration with the University of Perugia in Italy, we are investigating the antioxidant vitamin E, which includes eight natural compounds, four tocopherols and four tocotrienols. Most research on vitamin E in relation to dementia and AD has focused primarily only on α-tocopherol, with conflicting findings. In the European AddNeuroMed Project—a multicenter longitudinal study—we found that diagnoses of AD and diagnoses of MCI were associated with low plasma tocopherol and tocotrienol levels¹. In the same population, we showed that the combined analysis of tocopherol and tocotrienol plasma levels and automated MRI measures can help differentiate people with AD and MCI from those who are cognitively normal, and to prospectively predict MCI conversion to AD². These studies suggest that different forms of vitamin E can be important for the onset and progression of AD.

b. Vitamin B12 and folate. Some earlier studies have found that low blood levels of vitamin B12 and folate and high concentrations of homocysteine are related to an increased risk of cognitive impairment and dementia, but evidence has been inconsistent. In the CAIDE population, we found that higher serum levels of homocysteine were associated with poorer cognitive performance during seven years of follow-up, even in older adults without dementia. In the same population, increased levels of serum folate and holotranscobalamin—the biologically active fraction of vitamin B12—were associated with better cognitive performances, even in people without dementia³. In a Finnish neuropathological study (Vantaa) in very old individuals (85+), preliminary results show that higher plasma homocysteine is associated with increased brain burden of β-amyloid and neurofibrillary tangles.

1. Mangialasche F, Xu W, Kivipelto M, Costanzi E, Ercolani S, Pigliautile M, et al. AddNeuroMed Consortium. Tocopherols and tocotrienols plasma levels are associated with cognitive impairment. Neurobiol Aging  2012; 33(10):2282-2290.
2. Mangialasche F, Westman E, Kivipelto M, Muehlboeck JS, Cecchetti R, Baglioni M, et al. The AddNeuroMed consortium. Classification and prediction of clinical diagnosis of Alzheimer’s disease based on MRI and plasma measures of α-/γ-tocotrienols and γ-tocopherol. J Intern Med [In press: online] 2013. Available from: doi: 10.1111/joim.12037
3. Hooshmand B, Solomon A, Kåreholt I, Rusanen M, Hänninen T, Leiviskä J, et al. Associations between serum homocysteine, holotranscobalamin, folate and cognition in the elderly: a longitudinal study. J Intern Med 2012; 271(2):204-212.