Leukocyte Telomere Length Is Related to Brain Parenchymal Fraction and Attention/Speed in the Elderly: Results of the Austrian Stroke Prevention Study

Abstract

There are controversial results if leukocyte telomere length (LTL) is related to structural brain changes and cognitive decline in aging. Here, we investigated the association between LTL and 1) global MRI correlates of brain aging such as brain parenchymal fraction (BPF) and white matter hyperintensities (WMH) load and Fazekas score as well as 2) global (g-factor) and domain-specific cognition such as attention/speed, conceptualization, memory, and visuopractical skills. In total, 909 participants of the Austrian Stroke Prevention Study with LTL, MRI, and cognitive tests were included. There were 388 (42.7%) men, and the mean age was 65.9 years. Longer LTL was significantly associated with larger BPF (b = 0.43, p < 0.001), larger WMH load (b = 0.03, p = 0.04), and score (b = 0.05, p = 0.04) after adjusting for age, sex, vascular risk factors, and ApoE4 carrier status. The effect on BPF was more significant in the subgroups of women (b = 0.51, p = 0.001), age >65 years (b = 0.58, p = 0.002), BMI ≥ 25 (b = 0.40, p = 0.004), education ≤10 years (b = 0.42, p = 0.002), hypertensives (b = 0.51, p = 0.001), cardiovascular disease (CVD) (b = 0.58, p = 0.005), non-diabetics (b = 0.42, p < 0.001), and Apoe4 non-carriers (b = 0.49, p < 0.001). The effect on WMH was significant within the hypertensives (load: b = 0.04, p = 0.02), non-diabetics (load:b = 0.03, p = 0.01; score: b = 0.06, p = 0.02), in those with education ≤10 years (load: b = 0.03, p = 0.04; score: b = 0.07, p = 0.02), in ApoE4 non-carriers (load: b = 0.03, p = 0.02; score: b = 0.07, p = 0.01) and in subjects without CVD (score: b = 0.06, p = 0.05). We only observed a significant association between LTL and the cognitive domain of attention/speed, which was confined to the subgroups of BMI ≥ 25 (b = 0.04, p = 0.05) and education ≤10 years (b = 0.04, p = 0.05). The effect of LTL on attention/speed was partly mediated in both subgroups by BPF (b = 0.02, 95% CI = 0.01:0.03) when tested by bootstrapping. Our results support a strong protective role of longer LTL on global brain volume which in turn may contribute to better cognitive functions, especially in the attention/speed domain in the elderly.

Molecular and cellular pathways contributing to brain aging

“…They also provided evidence that suggests non-replicative neurons involved in the age-related telomere erosion procedure detected in the brain [ 158 ]. However, there are controversial reports describing leukocyte telomere length (LTL) associated with structural alterations to the brain and decreased cognitive capacity during aging [ 159 , 160 ].…”

“…Gampawar et al reported a highly unique link between LTL and brain parenchymal fraction (BPF) in the elderly. Also, they found that Longer LTL is connected with a larger brain and with better cognitive functioning in the attention/speed mediated by BPF [ 159 ]. In another study by Puhlmann et al, short-term LTL change was connected with structural brain alteration [ 160 ].…”

Investigating the Role of Leukocyte Telomere Length in Treatment-Resistant Depression and in Response to Electroconvulsive Therapy

“…The correlation between LTL and telomere dynamics in the central nervous system has been largely debated, but there is agreement in that TL in whole blood correlates with TL in most other tissues, including the brain [88]. While it is recognized that important differences exist in telomere biology and length in the different tissues of the human body, several studies suggest that LTL is significantly correlated with region-specific and total brain volume [89]. Interestingly, it has been suggested that shorter LTL is significantly associated with reduced size of the hippocampus [90].…”

Mid-life leukocyte telomere length and dementia risk: a prospective cohort study of 435,046 UK Biobank participants

“…11 Recent meta-analyses reported that longer TL was associated with better general cognition 12 and performance in several cognitive domains. 13,14 Few population-based studies have explored TL in relation to brain MRI imaging features. [14][15][16] A recent meta-analysis showed that longer leukocyte TL is associated with whole brain and hippocampus volumes but not with white matter hyperintensities (WMH).…”