Subcortical ischemic vascular cognitive impairment (SIVCI) is the most common form of vascular cognitive impairment. Exercise is a potentially effective intervention for SIVCI. However, the mechanisms through which exercise promotes brain health and cognitive function are not well understood. Telomere length restoration and an increased capacity for cellular proliferation may provide a putative mechanism. Therefore, in this exploratory study we aimed to 1) assess the effect of a resistance training program on leukocyte telomere length; and 2) determine whether telomere length and/or change in telomere length is related to intervention response (i.e., change in cognitive function and/or brain structure). The sample consists of a subset of participants from a 12-month single-blinded, randomized controlled trial (ClinicalTrials.gov Identifier: NCT02669394). Participants (N = 91) were randomized to twice-weekly resistance training (RT) or an active control group (balance and tone exercises; BAT). Study eligibility included: 1) age 55 years and older; 2) magnetic resonance imaging (MRI) evidence of cerebral small vessel disease; 3) mild cognitive impairment; and 4) the absence of dementia. We measured participants’ leukocyte (blood) telomere length at baseline, 6 months, and 12 months, using a qPCR-based method. The intervention outcomes include cognitive function measured by the Alzheimer’s Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-13 with additional cognitive tests) and structural brain magnetic resonance imaging (MRI) markers of SIVCI (e.g., white matter hyperintensities). We have generated telomere length data, demonstrating very good reproducibility with an intraclass correlation coefficient (ICC) of 0.853 [0.772, 0.907]. We will present findings that provide novel insights into the usefulness of telomere length as a predictive biomarker for intervention response. Furthermore, our work will contribute to the mechanistic understanding of exercise-induced benefits for cognitive and brain health in SIVCI. To our knowledge, this is the first study to investigate the role of telomere length in the efficacy of an exercise intervention for vascular cognitive impairment. This could inform the development of personalised interventions and aid the discovery of novel therapeutic targets.

BackgroundTelomere length (TL) has been linked to cognitive function, decline and dementia. This study aimed to explore whether both measured TL and genetic disposition for TL predict dimensions of cognitive performance in a longitudinal sample of older UK adults.MethodsWe analysed data from PROTECT study participants aged ≥50 years without a dementia diagnosis, who had completed longitudinal cognitive testing. We calculated polygenic scores for telomere length (PGS-TL) for 7,877 participants and measured relative telomere length (RTL) in a subgroup of 846 participants using DNA extracted from saliva samples collected within 6 months either side of their baseline cognitive testing. Latent growth models were used to examine whether RTL and PGS-TL predict both baseline and longitudinal changes in cognitive performance (4 time-points, annually).ResultsIn the whole sample, we did not observe significant associations between either measure of telomere length and initial or longitudinal changes in cognitive performance. Stratifying by median age, in older adults (≥ ∼62 years), longer baseline RTL showed a nominal association with poorer baseline verbal reasoning performance (n = 423, Mintercept = 47.58, B = −1.05, p = .011) and PGS-TL was associated with performance over time (n = 3,939; slope factor, Mslope = 3.23, B = −0.45, p = .001; slope2 factor, Mslope2 = 0.21, B = 0.13, p = .002).ConclusionOur findings suggest either the absence of a significant relationship between telomere length (RTL and PGS-TL) and cognitive performance (baseline and change over time), or possibly a weak age-dependent and domain-specific relationship, in older adults of European ancestry. More research is needed in representative and ancestrally diverse samples over a longer assessment period. Alternative biological ageing indicators may still provide utility in the early detection of individuals at risk for cognitive decline (e.g., pace-of ageing epigenetic clocks).

IntroductionPrevious studies have shown associations between cognitive function and C-reactive protein (CRP) levels in older adults. Few studies have considered the extent to which a genetic predisposition for higher CRP levels contributes to this association.MethodsData was analyzed from 7,817 UK participants aged >50 years as part of the PROTECT study, within which adults without dementia completed a comprehensive neuropsychological battery. We constructed a polygenic risk score (PRS-CRP) that explained 9.61% of the variance in serum CRP levels (p = 2.362 × 10−7) in an independent cohort. Regressions were used to explore the relationship between PRS-CRP and cognitive outcomes.ResultsWe found no significant associations between PRS-CRP and any cognitive measures in the sample overall. In older participants (>62 years), we observed a significant positive association between PRS-CRP and self-ordered search score (i.e., spatial working memory).ConclusionWhilst our results indicate a weak positive relationship between PRS-CRP and spatial working memory that is specific to older adults, overall, there appears to be no strong effects of PRS-CRP on cognitive function.

Background The COVID-19 pandemic has affected all our lives, not only through the infection itself but also through the measures taken to control the spread of the virus (e.g. lockdown). Aims Here, we investigated how the COVID-19 pandemic and unprecedented lockdown affected the mental health of young adults in England and Wales. Method We compared the mental health symptoms of up to 4773 twins in their mid-20s in 2018 prior to the COVID-19 pandemic (T1) and during four-wave longitudinal data collection during the pandemic in April, July and October 2020, and in March 2021 (T2–T5) using phenotypic and genetic longitudinal designs. Results The average changes in mental health were small to medium and mainly occurred from T1 to T2 (average Cohen d = 0.14). Despite the expectation of catastrophic effects of the pandemic on mental health, we did not observe trends in worsening mental health during the pandemic (T3–T5). Young people with pre-existing mental health problems were disproportionately affected at the beginning of the pandemic, but their increased problems largely subsided as the pandemic persisted. Twin analyses indicated that the aetiology of individual differences in mental health symptoms did not change during the lockdown (average heritability 33%); the average genetic correlation between T1 and T2–T5 was 0.95, indicating that genetic effects before the pandemic were substantially correlated with genetic effects up to a year later. Conclusions We conclude that on average the mental health of young adults in England and Wales has been remarkably resilient to the effects of the pandemic and associated lockdown.

Genome-wide association (GWA) studies have uncovered DNA variants associated with individual differences in general cognitive ability ( g ), but these are far from capturing heritability estimates obtained from twin studies. A major barrier to finding more of this ‘missing heritability’ is assessment––the use of diverse measures across GWA studies as well as time and the cost of assessment. In a series of four studies, we created a 15-min (40-item), online, gamified measure of g that is highly reliable (alpha = 0.78; two-week test-retest reliability = 0.88), psychometrically valid and scalable; we called this new measure Pathfinder. In a fifth study, we administered this measure to 4,751 young adults from the Twins Early Development Study. This novel g measure, which also yields reliable verbal and nonverbal scores, correlated substantially with standard measures of g collected at previous ages ( r ranging from 0.42 at age 7 to 0.57 at age 16). Pathfinder showed substantial twin heritability (0.57, 95% CIs = 0.43, 0.68) and SNP heritability (0.37, 95% CIs = 0.04, 0.70). A polygenic score computed from GWA studies of five cognitive and educational traits accounted for 12% of the variation in g , the strongest DNA-based prediction of g to date. Widespread use of this engaging new measure will advance research not only in genomics but throughout the biological, medical, and behavioural sciences.

In the 21 st century, emerging adulthood has stretched from the late teens through the twenties. Although this extended transition to adulthood can create stress, it can also offer opportunities to explore vocations and relationships that provide a better fit to individuals’ proclivities, including their genetic propensities. Here we report the results of the first systematic investigation of genetic and environmental influences on 57 psychological traits covering major issues in emerging adulthood such as aspirations, thoughts and attitudes, relationships and personality. We also investigate how these traits relate to physical and mental health, educational attainment and wellbeing using a sample of nearly 5000 pairs of UK twins aged 21-25 from the Twins Early Development Study. All 57 traits showed significant genetic influence, with an average heritability of 34% (SNP heritability ∼10%). Most of the variance (59% on average) was explained by non-shared environmental influences. These diverse traits were associated with mental health (average correlation .20), wellbeing (.16), physical health (.12) and educational attainment (.06). Shared genetic factors explained the majority of these correlations (∼50%). Together, these emerging adulthood traits explained on average 30% of the variance in the outcomes (range = 8 to 69%), suggesting that these traits relate to the outcomes additively. We conclude that the environmental uncertainties of emerging adulthood in the 21 st century do not diminish the importance of genetics. As adolescents travel down long and winding roads to adulthood, their trip is substantially influenced by genetic proclivities that nudge them down different paths leading to different destinations.

We investigated how the COVID-19 crisis and the extraordinary experience of lockdown affected young adults in England and Wales psychologically. One month after lockdown commenced (T2), we assessed 30 psychological and behavioural traits in 4,000 twins in their mid-twenties and compared their responses to the same traits assessed in 2018 (T1). Mean changes from T1 to T2 were modest and inconsistent: just as many changes were in a positive as negative direction. Twin analyses revealed that genetics accounted for about half of the reliable variance at T1 and T2. Genetic factors correlated on average .86 between T1 and T2 and accounted for over half of the phenotypic stability. Systematic environmental influences had negligible impact on T1, T2 or T2 change. Rather than the crisis fundamentally changing people psychologically, our results suggest that genetic differences between individuals play a fundamental role in shaping psychological and behavioural responses to the COVID-19 crisis.