December 18, 2012

OPTIMA:The Early Studies

The OPTIMA Study (Oxford Project To Investigate Memory and Aging):

The observation of elevated serum homocysteine levels in patients with clinically diagnosed Alzheimer's Disease (initially reported by Regland et al (Dementia 1990: 1:272-7) and later by McCaddon et al (Int.J.Ger.Psych 1998:13:235-9), was confirmed in patients with histopathologically confirmed Alzheimers Disease by the Oxford Project to Investigate Memory and Aging (OPTIMA) (Clarke et al. Arch.Neurol. 1998 55:1449-1455). This is a key study and worthy of further discussion here.

Why was OPTIMA important?

The OPTIMA team measured serum homocysteine levels in 164 patients aged 55 years or older with a clinical diagnosis of dementia of Alzheimer type and 108 healthy control subjects.  One of the key features of OPTIMA's work was that the patient group included 76 patients with histopathologically confirmed Alzheimer's Disease.

What did OPTIMA find?

OPTIMA found that blood homocysteine levels were significantly higher, and blood folic acid and vitamin B12 levels significantly lower, in patients with confirmed Alzheimer's Disease.  The odds ratio (or "risk") of confirmed Alzheimer's Disease for individuals with a homocysteine level greater than 14 micromol/L compared with those with a homocysteine less than 11 micromol/L was 4.5 (..that is, they were nearly 5 times more likely to have Alzheimer's Disease!)

Cause or Effect?

Homocysteine levels were unaltered by duration of symptoms, and were stable for several years afterwards.  Also, in a 3-year follow-up of patients with X ray evidence, disease progression was greater among those with higher homocysteine levels.  The OPTIMA team concluded that low blood levels of folate and vitamin B12 and elevated homocysteine levels were associated with Alzheimer's Disease.

Notably, individuals with higher homocysteine at presentation showed a much more rapid progression of Alzheimer's disease over a three-year period.

In later Blog Updates we will look at confirmatory evidence that high homocysteine is a strong causative risk factor for Alzheimer's Disease.

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