Apo E-4 and Memory Function in Non-Demented Middle-Aged Individuals
Abstract & Commentary
Synopsis: Having the gene for apolipoprotein E-4, an important biological marker for Alzheimer’s disease, is associated with subjective and objective mild memory difficulties in non-demented middle aged individuals.
Source: Small GW et al. Memory self-appraisal in middle-aged and older adults with the apolipoprotein E-4 allele. Am J Psychiatry 1999;156:1035-1038.
Alzheimer’s disease continues to be the leading cause of late-life dementia. Recent research has revealed that the gene for Apo E-4 is a powerful predictor of both hereditary and sporadic Alzheimer’s disease. Apolipoproteins are associated with B-A4 amyloid fibrils. Combining the Apo E-4 marker with clinical findings has improved diagnostic certainty in Alzheimer patients. The purpose of the present study was to examine whether the gene for apolipoprotein E-4 is associated with memory changes in younger patients with subjective memory complaints.
Small and colleagues recruited 39 subjects (22 women, 17 men; age range, 50-82) who responded to advertisements for a study of mild memory difficulties. They screened 180 subjects for treatable dementing illness, neurological or psychiatric disorders, and whether they were receiving psychotropic medications. Small et al excluded 141 subjects, leaving the study cohort of 39 subjects. Participating subjects then underwent neurocognitive testing and self-rating scales of memory function. Subjects with the Apo E-4 genotypes were identified through standard DNA screening methods.
Small et al then compared the findings for memory/cognitive functioning in the group with the allele for Apo E-4 vs. those without the allele. Statistically significant differences emerged for several measures of memory functioning, particularly in those 27 subjects between the ages of 55-74 (the association between Apo E-4 and Alzheimer’s disease is highest in this age group). Most of the significant differences were of low magnitude, except for marked differences in "retrospective functioning," a subjective measure of a person’s perceived loss of memory function over time. Small et al candidly described the several significant flaws in study design, and conclude their paper with the suggestion that combining measures of memory function with screening for Apo E-4 or other genetic predictors of Alzheimer’s disease may have merit in predicting who will subsequently develop Alzheimer’s disease.
Comment by Andrew L. Stoll, MD
Despite the considerable methodological limitations of the present study, the findings point to the potential value of combining clinical and even subjective measures of memory functioning with a simple genetic screening test. Longer term follow-up studies are underway by Small et al and other groups of investigators, and these studies may help pin down which aspect of neurocognitive functioning or subjective memory truly predicts which patients are at highest risk for developing Alzheimer’s disease. Combining these data with even more sensitive and specific measures of which genotype(s) or phenotype(s) are at highest risk will also surely improve diagnostic accuracy. In the near future, emerging prophylactic therapies against Alzheimer’s disease can target those individuals identified as a high risk for developing this devastating dementing illness.
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