• 400 million people are at risk of developing dementia
• The world faces a growing epidemic as the population ages:
• 20 million people worldwide are currently affected
• 60 million people will be affected by 2030
• This will place a significant burden on health care and social security

We need to find ways to reduce the incidence of dementia.  One approach is to identify modifiable risk factors.  One such factor, discovered by COBALZ, is an elevated blood level of homocysteine

COBALZ has developed new compositions to lower homocysteine and treat and prevent cognitive decline.  Potentially these will protect millions of people worldwide from developing dementia, eventually saving society large sums of money: about $10 billion annually in the USA and £1 billion annually in the UK

Dementia is a multifactorial disease; some risk factors are non-genetic.  One such factor - elevated blood levels of homocysteine - was discovered by the COBALZ research team in 1998.  Elevated homocysteine is a risk factor for vascular disease, including stroke.  Raised levels are now known to be associated with confirmed Alzheimer’s disease and vascular dementia and with a more rapid rate of disease progression.  Almost 16% of incident dementia may be due to raised homocysteine

There are biologically plausible mechanisms for a link between elevated plasma homocysteine levels and dementia:

• Homocysteine is neurotoxic and interacts with beta-amyloid
• Homocysteine is a vascular toxin and a risk factor for cerebrovascular disease
• Homocysteine elevation is associated with brain atrophy
• Oxidised forms of homocysteine are potent excitotoxins 

Blood levels of homocysteine are mainly determined by folate and vitamin B12 status; levels can usually be lowered by supplementation with these vitamins

It is not yet clear whether lowering homocysteine treats or prevents associated cognitive decline.  Although proper trials have not yet been performed the few small studies to date using currently available forms of B vitamins have yielded generally disappointing results

Dementia and aging are also associated with increased free radicals and decreased cellular defences.  This ‘oxidative stress’ contributes to nerve cell death and damages vascular endothelium

The relationship between homocysteine and dementia additionally reflects the effects of this stress on homocysteine metabolism

Oxidative stress impairs the ability of methionine synthase to lower homocysteine (See figure).  B12 activation is also impaired and folate is irreversibly oxidised.  These ‘functional’ deficiencies are restricted to neurovascular tissue.  In these situations it is not sufficient to simply lower homocysteine by B vitamin supplementation.  The adverse effects of oxidative stress on B12 and folate also have to be addressed

COBALZ has found that lowering homocysteine by conventional vitamin supplementation alone does not improve symptoms

However, the addition of glutathione precursors results in prompt, striking and sustained clinical improvement

COBALZ is now evaluating novel methods of treating and preventing dementia based upon these discoveries