Aging in Neurofibromatotis 1 (NF1): Survival and Comorbidity According to US Death Certificates. B.A. Carnes, J.J. Mulvihill, T.A. Teasdale, M.A. Grim, J.L. Mester Geriatric Medicine, Oklahoma University Helath Sciences Center, Oklahoma City, OK.
To gain insight into issues of aging in neurofibromatosis 1 (NF1), US multiple cause of death files for 1988-1998 (24.2 million death certificates) were examined in order to compare survival and morbidity characteristics between young and old NF1 decedents and between these groups and their age-matched non-NF1 counterparts. Median age at death for NF1 decedents was 54 for males and 60 for females. Although males with NF1 as a concomitant disorder died 7 years earlier than their female counterparts, the gender gap was eliminated for those dying from NF1 as the cause of death. Recursive partitioning revealed that decedents dying with NF1 at older ages had less cancer (connective tissue tumor and brain neoplasm) and congestive heart failure than those dying at younger ages; whereas those dying because of NF1 at older ages had less cardiovascular (cerebrovascular, chronic ischemic and congestive heart) disease and pulmonary disease (COPD). Logistic regression analyses, stratified by sex, confirmed that young and old NF1 decedents can be distinguished (area under the ROC = 0.77) purely on the basis of their comorbidity profiles (array of ICD codes). Conditional logistic regression and standardized death rate ratios revealed that younger NF1 decedents have a greater risk of intrinsic (non-accidental) death than older NF1 decedents, relative to their age- and sex-matched non-NF1 counterparts. These findings suggest that younger NF1 decedents may have a more severe form of the comorbidities associated with this single gene disorder. Parallel analyses are underway for Canadian and Danish death certificates, as part of a large project to identify geriatric issues in this common Mendelian disorder. (Funded in part with DOD-US Army Neurofibromatosis Program grant W81XWH-06-1-0465).