Leukocyte Telomere Length is Linked to Vascular Risk Factors Not to Alzheimer's Disease in the VITA Study

Association of telomere shortening with overall dementia or Alzheimer's disease is described controversially and the pathophysiologic relevance is unclear. Whether patients, suffering from pure probable Alzheimer's disease or pure vascular dementia, have shorter leukocyte telomeres than cognitively healthy controls was determined. Leukocyte telomere lengths (LTLs) of 597 participants of the VITA study (longitudinal community-based age-cohort [mean 75.7 (±0.45) years] study: 243 male; 578 non-demented at baseline) were compared with different aspects of cognition, risk factors of dementia and survival. LTLs of 264 persons cognitively healthy at baseline (mild cognitive impaired excluded) and all follow-ups (mean = 5643 bp, SD = 736) did not show any difference to LTLs of 43 incident pure possible (mean = 5548 bp; SD = 666) or 34 incident pure probable Alzheimer's diseases (mean = 5712 bp; SD = 695; post hoc Dunnett test: MD = -95; SE = 119; p = 0.67 and MD =+68.3; SE = 132; p = 0.84, res.). 264 stably cognitively healthy showed a trend to longer telomeres than 6 incident vascular dementias (mean = 5643 bp, SD = 736 vs mean = 5101 bp, SD = 510; t test: T = 1.8; df = 268; p = 0.07). Males (n = 243; mean = 5470 bp; SD = 684) had significantly shorter telomeres than females (n = 354; mean = 5686 bp; SD = 714; t test: T = -3.7; df = 595; p = 0.0001) and died significantly earlier (113.7 vs 130.1 months: Log Rank Chi square = 12.2; p = 0.0001). Shorter telomeres were associated with prevalence of more than one vascular risk factor (n = 587; mean = 5728; SD = 723 vs mean = 5533; SD = 691; t test: T = 3.1; df = 576; p = 0.002) and, as a trend, with poorer survival (Cox Regression: Wald = 4.9; p = 0.026; OR = 0.98; 95% CI 0.96-0.99). In 75.7 years old persons, no association of LTL with incident pure Alzheimer's disease was found. Significantly shorter telomeres were associated with sum of vascular risk factors, males and early mortality in males. Exclusion of mixed dementias may improve the search for risk factors more specific for Alzheimer's disease.