Shorter telomeres are associated with mortality in those with APOE epsilon4 and dementia.
OBJECTIVE
Reduced telomere length may be a marker of biological aging. We hypothesized that telomere length might thus relate to increased risk for dementia and mortality.


METHODS
This nested case-control study used stored leukocyte DNA from 257 individuals (mean age, 81.4 +/- 7.9 years; 64.6% female; 44.7% Hispanic, 33.5% non-Hispanic black, and 21.8% non-Hispanic white). Our assay used real-time polymerase chain reaction, with two separate reactions amplifying telomere sequence and reference single copy gene (ribosomal-protein-P0), providing a calculated telomere-to-single copy gene (T/S) ratio.


RESULTS
Mean telomere length was shorter among subjects dying during follow-up than in those surviving (0.453 +/- 0.211 vs 0.525 +/- 0.226 [+/- standard deviation]; p < 0.009). It was also shorter in those with Alzheimer's disease compared with control subjects (0.458 +/- 0.207 vs 0.516 +/- 0.229; p < 0.03). For participants with Alzheimer's disease, compared with those with the longest telomeres, the mortality odds ratio (OR) was 4.8 (95% confidence interval [CI], 1.7-13.8) in those with intermediate-length telomeres and 7.3 (95% CI, 2.4-22.0) in those with the shortest telomeres. The presence of an epsilon4 allele also increased the mortality OR, with an OR of 5.8 (95% CI, 1.3-26.4) for intermediate-length telomeres and an OR of 9.0 (95% CI, 1.9-41) for the shortest telomeres.


CONCLUSIONS
Our findings suggest that leukocyte telomere length is related to both dementia and mortality and may be a marker of biological aging.
Honig
Lawrence S
LS
Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H. Sergievsky Center, New York, NY, USA. lh456@columbia.edu
Schupf
Nicole
N
Lee
Joseph H
JH
Tang
Ming X
MX
Mayeux
Richard
R
D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D004247:DNA / Q000235:genetics; D003704:Dementia / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007962:Leukocytes / Q000473:pathology / Q000648:ultrastructure; D016015:Logistic Models; D008297:Male; D009519:New York City; D012306:Risk; D016615:Telomere / Q000473:pathology* / Q000648:ultrastructure*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D004247:DNA