Daily Archives: January 12, 2009

APOE Status and Association to Learning and Memory

The featured paper is ‘APOE status and its association to learning and memory performance in middle aged and older Norwegians seeking assessments for memory deficits’ by Wehling and colleagues and freely available here.

The authors examined the hypothesis that in people with Mild Cognitive Impairment, the APOE e4 gene would predict performance on memory tasks. The researchers selected a sample from the Norwegian population as the allele is more prevalent in this population. People aged 50-75 who were referred by their ‘primary physician’ to ‘a clinical research project’ (presumably this group as there was no mention of sampling subjects from a larger research study). There were a number of exclusion criteria which included neurological and psychiatric illnesses which could ‘affect cerebral function’. There are nevertheless a number of non-neurological and non-psychiatric illnesses which may also affect cerebral function (e.g. endocrine disorders) whilst it is difficult to think of psychiatric illnesses which do not affect cerebral function. The principle however appears to be that of selecting out people where cognition is not obviously affected by clearly identified illness so as to have a better chance of elucidating the gene relationship with the neuropsychological function. There are many factors which can confound this relationship and thus the most convincing studies are those with large sample sizes. The APOE4 does have the advantage though of a large supporting evidence base using many different paradigms. The subjects were administered a large battery of neuropsychological tests including an assessment of IQ, California Verbal Learning Test, Rey Complex Figure Test, Digit Symbol Test, Trail Making Test and verbal fluency. The California Verbal Learning Test scores were used in the definition of Amnestic Mild Cognitive Impairment. The APOE e4 carriers were then compared with non-carriers.

There were found to be no differences in IQ between the two groups although there was a difference of just under 1 point in MMSE scores which reached significance (p=0.03). If this is considered in the context of being an average for a sample (with over 30 in each group) then this difference can be seen to be meaningful. However it is with the more detailed measurements of performance that there were more interesting results. Thus there were significant results on many subscores of the California Verbal Learning Test including the List A Trial 1 recall (p=0.04), Total Learning (trial 1-trial 5) (p=0.02), Intrusions Learning (p=0.03) and percentage consistency (0.01). An ANOVA was performed to look for the effects of age and gender on CVLT performance and there was found to be no significant interaction.

What about the APOE e4 homozygous group? This group should have a much lower performance on the memory tests as they have two copies of the gene. The data on this group would therefore have let us examine the null hypothesis from yet another perspective. However the results for this group were not presented separately! Perhaps the small number in this group didn’t allow for any significance results to emerge.

The study results are clearly and simply presented and this study contributes more evidence towards an important relationship between the APOE e4 gene and memory.



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