The apolipoprotein E ϵ4 allele and incident Alzheimer’s disease in persons with mild cognitive impairment

Abstract

Possession of one or more copies of the apolipoprotein E (APOE) ϵ4 allele is a known risk factor for Alzheimer’s disease (AD), but it is uncertain whether the ϵ4 allele is associated with disease incidence among persons with mild cognitive impairment (MCI). We addressed this issue with data from the Religious Orders Study. Participants were 181 older Catholic clergy members who met criteria for MCI based on a uniform structured clinical evaluation; 56 (30.9%) had at least one ϵ4 allele. Clinical evaluations, which included clinical classification of dementia and AD, were repeated annually. During a mean of 5.7 years of observation, 79 persons (43.6%) developed AD. In a proportional hazards model that controlled for age, sex, and education, possession of an ϵ4 allele was associated with a 93% increase in the risk of developing Alzheimer’s disease (95% CI: 1.02, 2.63). There was a marginally significant reduction in the effect of ϵ4 in older compared to younger participants (p = .053). The results suggest that possession of an ϵ4 allele does increase risk of AD in persons with MCI.

The authors thank the hundreds of nuns, priests, and brothers from the following groups participating in the Religious Orders Study: archdiocesan priests, Chicago, IL, Dubuque, IA, and Milwaukee, WI, Benedictine monks, Lisle, IL, and Collegeville, MN, Benedictine Sisters, Erie, PA: Benedictine Sisters of the Sacred Heart, Lisle, IL, Capuchins, Appleton, WI, Christian Brothers, Chicago, IL, and Memphis TN, diocesan priests, Gary, IN, Dominicans, River Forest, IL, Felician Sisters, Chicago, IL, Franciscan Handmaids of Mary, New York NY; Franciscans Chicago, IL, Holy Spirit Missionary Sisters, Techny IL, Maryknolls, Los Altos, CA, and Maryknolls, NY, Norbertines, De Pere, WI, Oblate Sisters of Providence, Baltimore, MD, Passionists, Chicago, IL, Presentation Sisters, BVM, Dubuque, IA, Servites, Chicago, IL, Sinisinawa Dominican Sisters, Chicago, IL, and Sinsinawa WI, Sisters of Charity, BVM, Chicago, IL, and Dubuque IA, Sisters of the Holy Family, New Orleans, LA, Sisters of the Holy Family of Nazareth, Des Plaines, IL, Sisters of Mercy of the Americans, Chicago, IL, Aurora, IL, and Erie, PA, Sisters of St. Benedict, St. Cloud, MN and St. Joseph, MN, Sisters of St. Casimir Chicago, IL, Sisters of St. Francis of Mary Immaculate, Joliet, IL, Sisters of St. Joseph of La Grange, La Grange Park, IL, Society of Divine Word, Techny, IL, Trappists, Gethsemane, KY and Peosta, IA, and Wheaten Franciscan Sisters, Wheaten, IL. They also thank Julie Bach MSW, coordinator of the Religious Orders Study, Beth Howard, Coordinator of the Rush Alzheimer’s Disease Center Laboratory, and George Dombrowski MS and Greg Klein for data management.

This research was supported by National Institute on Aging grants R01 AG1589, P30 AG10161, P01AG09466, P01AG14449

Notes

The authors thank the hundreds of nuns, priests, and brothers from the following groups participating in the Religious Orders Study: archdiocesan priests, Chicago, IL, Dubuque, IA, and Milwaukee, WI, Benedictine monks, Lisle, IL, and Collegeville, MN, Benedictine Sisters, Erie, PA: Benedictine Sisters of the Sacred Heart, Lisle, IL, Capuchins, Appleton, WI, Christian Brothers, Chicago, IL, and Memphis TN, diocesan priests, Gary, IN, Dominicans, River Forest, IL, Felician Sisters, Chicago, IL, Franciscan Handmaids of Mary, New York NY; Franciscans Chicago, IL, Holy Spirit Missionary Sisters, Techny IL, Maryknolls, Los Altos, CA, and Maryknolls, NY, Norbertines, De Pere, WI, Oblate Sisters of Providence, Baltimore, MD, Passionists, Chicago, IL, Presentation Sisters, BVM, Dubuque, IA, Servites, Chicago, IL, Sinisinawa Dominican Sisters, Chicago, IL, and Sinsinawa WI, Sisters of Charity, BVM, Chicago, IL, and Dubuque IA, Sisters of the Holy Family, New Orleans, LA, Sisters of the Holy Family of Nazareth, Des Plaines, IL, Sisters of Mercy of the Americans, Chicago, IL, Aurora, IL, and Erie, PA, Sisters of St. Benedict, St. Cloud, MN and St. Joseph, MN, Sisters of St. Casimir Chicago, IL, Sisters of St. Francis of Mary Immaculate, Joliet, IL, Sisters of St. Joseph of La Grange, La Grange Park, IL, Society of Divine Word, Techny, IL, Trappists, Gethsemane, KY and Peosta, IA, and Wheaten Franciscan Sisters, Wheaten, IL. They also thank Julie Bach MSW, coordinator of the Religious Orders Study, Beth Howard, Coordinator of the Rush Alzheimer’s Disease Center Laboratory, and George Dombrowski MS and Greg Klein for data management.

This research was supported by National Institute on Aging grants R01 AG1589, P30 AG10161, P01AG09466, P01AG14449