Homocysteine, cognition and dementia

[Truncated abstract] Background: Dementia is a leading cause of worldwide disability and mortality and is predicted to affect nearly half a million Australians by 2031. The consequences of dementia are wide reaching, impacting not only on the individual and their family, but also on society as a whole. There is currently no disease-modifying treatment available and unfortunately little evidence that such a treatment will be forthcoming in the near future. The identification of key risk factors and in particular, potentially modifiable factors has thus become a health imperative. Over the past two to three decades, high total plasma homocysteine (tHcy; a non-essential amino acid) has been proposed as a risk factor for the development of cognitive impairment and dementia. This is important, as tHcy can be reliably lowered through simple supplementation with vitamin B12, B6 and folic acid, making it a potentially easily modifiable risk factor for dementia. Hypotheses: The studies of this thesis were designed to test the hypotheses that high tHcy and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism increase the risk of cognitive impairment, grey matter atrophy and dementia in older adults and that lowering tHcy through daily supplementation with vitamin B12, B6 and folic acid reduces this risk and improves cognitive performance.