Different Demographic, Genetic, and Longitudinal Traits in Language versus Memory Alzheimer's Subgroups

Article type: Research Article

Authors: Mez, Jesse^{a; b; c; d; *} | Cosentino, Stephanie^{a; b; c} | Brickman, Adam M.^{a; b; c} | Huey, Edward D.^{a; b; c; f} | Mayeux, Richard^{a; b; c; e; f}

Affiliations: [a] Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA | [b] Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA | [c] Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA | [d] Department of Biostatistics, Joseph P. Mailman School of Public Health, Columbia University, New York, NY, USA | [e] Department of Epidemiology, Joseph P. Mailman School of Public Health, Columbia University, New York, NY, USA | [f] Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA

Correspondence: [*] Correspondence to: Jesse Mez, Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA. Tel.: +1 212 305 8621; Fax: +1 212 305 2526; E-mail: [email protected].

Abstract: The study's objective was to compare demographics, APOE genotypes, and rate of rise over time in functional impairment in neuropsychologically defined language, typical, and memory subgroups of clinical Alzheimer's disease (AD). 1,368 participants from the National Alzheimer's Coordinating Center database with a diagnosis of probable AD (CDR 0.5–1.0) were included. A language subgroup (n = 229) was defined as having language performance >1 SD worse than memory performance. A memory subgroup (n = 213) was defined as having memory performance >1 SD worse than language performance. A typical subgroup (n = 926) was defined as having a difference in language and memory performance of <1 SD. Compared with the memory subgroup, the language subgroup was 3.7 years older and more frequently self-identified as African American (OR = 3.69). Under a dominant genetic model, the language subgroup had smaller odds of carrying at least one APOEε4 allele relative to the memory subgroup. While this difference was present for all ages, it was more striking at a younger age (OR = 0.19 for youngest tertile; OR = 0.52 for oldest tertile). Compared with the memory subgroup, the language subgroup rose 35% faster on the Functional Assessment Questionnaire and 44% faster on CDR sum of boxes over time. Among a subset of participants who underwent autopsy (n = 98), the language, memory, and typical subgroups were equally likely to have an AD pathologic diagnosis, suggesting that variation in non-AD pathologies across subtypes did not lead to the observed differences. The study demonstrates that a language subgroup of AD has different demographics, genetic profile, and disease course in addition to cognitive phenotype.

Keywords: African Americans, age of onset, Alzheimer's disease, aphasia, apolipoprotein E4, focal onset Alzheimer's disease, demographic factors, language, longitudinal studies, memory

DOI: 10.3233/JAD-130320

Journal: Journal of Alzheimer's Disease, vol. 37, no. 1, pp. 137-146, 2013