Dissociation of neuropathologic findings and cognition -: Case report of an apolipoprotein e ε2/ε2 genotype

Background: The apolipoprotein E (APOE) epsilon 2 allele has been suggested as having a protective effect and delaying the age at onset of Alzheimer disease. Objective: To describe a dissociation between neuropathologic findings with normal cognition in a woman with severe Alzheimer disease with the APOE epsilon 2/epsilon 2 genotype. Design: Case report from a community-based prospective study of persons 90 years or older (The 90+ Study). Participant: A 92-year-old woman without dementia with the APOE epsilon 2/epsilon 2 genotype who lived independently without significant cognitive or functional loss and was a participant in The 90+ Study. She died in December 2004, and postmortem examination of her brain was performed. Intervention: Neurologic examination and a battery of neuropsychological tests were performed 6 months and 1 month before death. Neuropathologic examination included Braak and Braak staging for senile plaques and neurofibrillary tangles. Results: Neuropathologic examination of the brain revealed advanced senile plaque and neurofibrillary tangle disease consistent with a high likelihood of Alzheimer disease. At clinical evaluation, the participant demonstrated no dementia and only mild cognitive deficits. Conclusions: The APOE genotype may have contributed to maintenance of cognition despite advanced neuropathologic findings of Alzheimer disease. This case suggests that the APOE epsilon 2 isoform may have a protective effect against cognitive decline in Alzheimer disease that may be independent from senile plaques and neurofibrillary tangles.