Short and long telomeres increase risk of amnestic mild cognitive impairment

Abstract

Peripheral blood telomere length has been associated with age-related conditions including Alzheimer’s disease (AD). This suggests that telomere length may identify subjects at increased risk of AD. Thus, we investigated the associations of peripheral blood telomere length with amnestic mild cognitive impairment (aMCI), a putative precursor of AD, among Mayo Clinic Study of Aging participants who were prospectively followed for incident aMCI. We matched 137 incident aMCI cases (mean age 81.1 years, [range 70.9–90.8]; 49.6% men) by age and sex to 137 cognitively normal controls. We measured telomere length (T/S ratio) at baseline and follow-up using quantitative PCR. Compared to the middle T/S quintile (Q3), the risk of aMCI was elevated for subjects with the shortest (Q1: HR, 2.85, 95% Confidence interval [CI] 0.98, 8.25; p = 0.05) and the longest telomere lengths (Q5: HR, 5.58, 95%CI, 2.21, 14.11; p = 0.0003). In this elderly cohort, short and long telomeres were associated with increased risk of aMCI. Our findings suggest that both long and short telomere lengths may play a role in the pathogenesis of aMCI, and may be markers of increased risk of aMCI.

Telomere Length, Long-Term Black Carbon Exposure, and Cognitive Function in a Cohort of Older Men: The VA Normative Aging Study

“…This pattern of associations, which we also observed for the interaction between BC and CRP in this study, suggests the existence of an activation threshold, which is typical in inflammatory responses, particularly if they—such as those elicited by traffic air pollution—are induced through the NF-κB pathway (Nam et al 2009). Of note, a previous study described an L-shaped association of TL with mild cognitive impairment; in particular, TL in the top quintile, but not in other quintiles, was associated with relative odds of both prevalent and incident mild cognitive impairment (Roberts et al 2014). Alternatively, our finding might reflect a saturation effect among individuals with shorter TL.…”

“…Telomere length (TL) has been shown to decrease non-linearly with age across different tissues, including blood leukocytes, in living organisms (Saretzki and Von Zglinicki 2002; Young 2010). Shorter leukocyte TL has been associated with age-related diseases, such as cardiovascular disease (Fyhrquist et al 2011), cancer (Artandi and DePinho 2010), and cognitive impairment (Roberts et al 2014), as well as with mortality (Svenson et al 2009), although one study reported opposing associations (Sanchez-Espiridion et al 2014). …”

Telomere Length and the Risk of Alzheimer’s Disease: The Rotterdam Study

“…Conversely, there is evidence that over-elongated telomeres represent pathological cell function with decreased DNA repair and increased cancer risk [9], which has also been shown in human embryonic stem cells [10], while "normally" long telomeres are protective, including against DNA damage. With respect to Alzheimer's disease, there is also evidence suggesting an increased risk of mild cognitive impairment related to both short and long telomeres [11]. Additionally, hippocampal cells of Alzheimer's disease brains are shown to have longer telomeres compared to control samples [12].…”

Evaluation of oxidative stress mechanisms and the effects of phytotherapic extracts on Parkinson's diseaseDrosophila PINK1B9model

“…Another study showed that both short and long telomeres increase risk of amnestic mild cognitive impairment (41). Furthermore, longer telomeres are often associated with an increased risk for different cancer types (42).…”