Clinical, Neuroimaging, and Environmental Risk Differences in Monozygotic Female Twins Appearing Discordant for Dementia of the Alzheimer Type

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Abstract
• Objective. —The study of monozgotic twins can elucidate possible environmental causes for a disease in genetically identical subjects. To this end, we studied a pair of monozygotic female twins appearing discordant for dementia of the Alzheimer type (DAT). Design. —Clinical and neuroimaging findings were compared in terms of potential environmental risk factors. Setting. —University referral center. Participants. —An 81-year-old female monozygotic twin pair. Outcome Measures. —Clinical assessments, standardized rating scales, and brain imaging studies, including magnetic resonance imaging, positron emission tomography, and electroencephalography, were performed. Neuropsychological tests were performed initially and after 1 year. Results. —Although DAT was confirmed clinically in only one twin, neuropsychological and brain imaging studies suggested that the unaffected twin may be developing the prodrome of DAT. The twins' varied life histories suggest that environmental risk factors may contribute to apparent discordance for DAT and possible delay in disease onset for the currently nondemented twin. Conclusions. —These results suggest that both genetic and nongenetic factors influence disease onset and expression. Moreover, review of previous reports of monozygotic twin pairs concordant or discordant for Alzheimer's disease, with adequate family history data, suggest a pattern indicating interactions among age at dementia onset, sex, and familiality. Such patterns point to hypotheses regarding neurobiologically meaningful Alzheimer's disease subgroups.

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