Dissociation of Neuropathologic Findings and Cognition

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Abstract
Background The apolipoprotein E (APOE) ε2 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 theAPOEε2/ε2 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 theAPOEε2/ε2 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 TheAPOEgenotype may have contributed to maintenance of cognition despite advanced neuropathologic findings of Alzheimer disease. This case suggests that theAPOEε2 isoform may have a protective effect against cognitive decline in Alzheimer disease that may be independent from senile plaques and neurofibrillary tangles.