Modelling Rates of Cognitive Decline in Patients with a Dementing Illness

Beaumont, Helen (2007). Modelling Rates of Cognitive Decline in Patients with a Dementing Illness. MPhil thesis The Open University.



Optima is an Oxford-based longitudinal study of people with dementia, and non-demented elderly. The results of cognitive tests of 123 Optima patients with dementia (age at first visit 44 - 89 years, mean 72.2; 76 females, 47 males; 2 - 2 1 visits, mean 7.9) are analysed. The test used was the cognitive component of the Cambridge Mental Disorders of the Elderly Examination (Camdex). The rate of decline varies markedly between patients; in their first year a few patients show an increased score; the mean decline is 14 Camcog points, and the maximum 61.

The decline of individual patients is modelled by fitting the test scores with the binomial or logistic variant of the general logistic model (as shown in figure 1.1), generally giving a good fit to the data. A method of centering the individual curves about the midpoint of the cognitive scale is developed, which puts patients on a common time-scale and allows all the data to be incorporated into a single fixed-effects model. This method has the power to look at many possible covariates and identify those which apparently have significant effects.

A random-effects model is then adopted (theoretically more plausible) to carry out a more rigorous analysis which confirms these results. Both models show the rate of decline is strongly affected by:

• Age at Camcog midpoint
• Initial homocysteine level
• APOE genotype
• Anti-cholinesterase drugs

In order to show the relative effects of these covariates the idea of the decline ratio, similar to the odds-ratio, is introduced. Its purpose is to quantify the effect of one variable on the progress of the disease, all other things being equal. Younger patients, those with the APOE44 allele and those without the APOE44 allele but with an initially high level of homocysteine, are more likely to have a rapidly progressing illness. Patients who take anticholinesterase drugs in the early stages of their illness are likely to show a slower decline.

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