Carriers of the apolipoprotein E (APOE) ε 4 allele experience faster age-related memory decline than noncarriers before age 60, despite having an ongoing normal clinical status, according to a study published in the July 16 New England Journal of Medicine.
Dr. Richard J. Caselli, MD, of the Mayo Clinic in Scottsdale, Arizona, and colleagues, recruited 815 cognitively normal persons between ages 21 and 97, and grouped them according to APOE ε 4 status (317 APOE ε 4 carriers; 498 noncarriers). Subjects were followed up with longitudinal neuropsychologic testing. Those who showed mild cognitive impairment (MCI) or dementia during follow-up were excluded. Rates of decline in predetermined cognitive measures between carriers and noncarriers of the APOE ε 4 allele were compared with use of a mixed model for longitudinal change with age.
Overall, carriers (79 homozygous, 238 heterozygous) were younger than noncarriers (mean age, 58.0 vs 61.4). It was more common for carriers to have a first-degree relative with dementia than for noncarriers (73.5% vs 52.8%), but adjustment for this did not significantly alter the results for any measure.
A significantly greater quadratic longitudinal effect of aging on the Auditory-Verbal Learning Test (AVLT-LTM) score was observed among APOE ε 4 carriers.
“The mixed model for the AVLT-LTM predicted a decline in scores for APOE ε 4 carriers beginning in their 50s (on the basis of a comparison of a predicted annual increase at age 50 with a predicted annual decline at age 60) and a decline in noncarriers beginning in their 70s,” Dr. Caselli and researchers stated.
A significant linear APOE ε 4 allele dose effect with quadratic age on the AVLT-LTM was observed between homozygotes and noncarriers, but not between heterozygotes and noncarriers. Dr. Caselli and colleagues noted that caution should be used when interpreting the results, due to the small size of the homozygous group. “The mixed model for the AVLT-LTM predicts a decline in scores for APOE ε 4 homozygotes starting in their 50s, a decline in scores for APOE ε 4 heterozygotes starting in their 60s, and a decline in scores for noncarriers starting in their 70s,” Dr. Caselli and coauthors stated.
The findings suggest that the APOE ε 4 allele is a risk factor for age-related memory decline, independent of MCI and dementia. “They also suggest that accelerated memory decline among persons with the APOE ε 4 allele may be caused by subclinical Alzheimer’s disease, since age-related memory decline was increased and visuospatial function was decreased in carriers of the APOE ε 4 allele.”