Aortic Stiffness and Age With Cognitive Performance Decline in the ELSA‐Brasil Cohort

Abstract

Background Increased aortic stiffness has been associated with cognitive decline and dementia, but the results are inconsistent. This study investigated the longitudinal association of aortic stiffness and age with decreased cognitive performance in 3 cognitive tests. Methods and Results This study included 6927 participants, with a mean age of 58.8 years at baseline (2008–2010), who participated in the second wave (2012–2014) of the ELSA ‐Brasil (Brazilian Longitudinal Study of Adult Health) (interval between visits ranging from 2–6 years). Cognitive performance was evaluated by Memory, Phonemic, and Semantic Verbal Fluency and Trail B Tests, applied at both cohort visits. Associations with the carotid‐femoral pulse wave velocity and age at baseline were investigated using linear models with mixed effects after adjusting for confounders. After all the adjustments, including for systolic blood pressure, the interaction term carotid‐femoral pulse wave velocity×time proved to be statistically significant for Memory and Verbal Fluency Tests, indicating that the higher carotid‐femoral pulse wave velocity at baseline was associated with a faster decline in cognitive performance in these tests between waves. The interaction term age×time was statistically significant for all cognitive tests, suggesting that increasing age at baseline was also associated with a faster decline in cognitive performance between waves. Conclusions In this relatively young cohort, and after a relatively short interval, an increased aortic stiffness at baseline was associated with a sharper decline in cognitive performances in memory and verbal fluency, regardless of systolic blood pressure levels. This study also showed that the decline in cognitive performance was faster among older individuals than among younger ones at baseline.

Association of Aortic Stiffness and Cognitive Decline: A Systematic Review and Meta-Analysis

“…Finally, we did not pool the correlation of aortic PWV and domains of cognitive function in longitudinal studies due to the limited available data. Since there were studies that showed a faster decline in several domains of cognitive function with higher aortic stiffness (Hajjar et al, 2016;Menezes et al, 2019), it would be more convincing if we further confirmed this longitudinal association in our quantitative analysis.…”

“…We also calculated the pooled ORs of continuous aortic PWV (m/s) to cognitive impairment or dementia. It showed that the cognitive impairment risk increased 3.9% (OR 1.039; 95% CI 1.005–1.073) per 1 m/s of aortic PWV increase from six studies (15,711 participants) reporting risk of cognitive impairment (Poels et al, 2007 ; Watson et al, 2011 ; Watfa et al, 2015 ; Pase et al, 2016a ; Araghi et al, 2019 ; Menezes et al, 2019 ). There were moderate heterogeneity and no publication bias ( Figure 4 , Supplementary Figure 6 ).…”

“…As shown in the diagram of the selection process ( Figure 1 ), among 2,869 records, 65 articles were evaluated based on full text. Finally, 39 studies were summarized for detailed review, including 28 studies with 29,955 participants from 14 different countries in the cross-sectional analysis (Hanon et al, 2005 ; Scuteri et al, 2005 ; Poels et al, 2007 ; Elias et al, 2009 ; Kearney-Schwartz et al, 2009 ; Triantafyllidi et al, 2010 ; Watson et al, 2011 ; Singer et al, 2013 ; Nilsson et al, 2014 , 2017 ; Zhong et al, 2014 ; Cooper et al, 2016 ; Geijselaers et al, 2016 ; Lim et al, 2016 ; Pase et al, 2016b ; Riba-Llena et al, 2016 ; Tasmoc et al, 2016 ; Kim et al, 2017 ; Meyer et al, 2017 ; Suleman et al, 2017 ; Karasavvidou et al, 2018 ; Kennedy et al, 2018 ; Muela et al, 2018 ; Araghi et al, 2019 ; DuBose et al, 2019 ; Palta et al, 2019 ; Dixon et al, 2020 ; Zijlstra et al, 2020 ) and 16 studies with 23,448 participants from seven different countries in the longitudinal analysis (Poels et al, 2007 ; Scuteri et al, 2007 , 2013 ; Waldstein et al, 2008 ; Watson et al, 2011 ; Zeki Al Hazzouri et al, 2013 ; Watfa et al, 2015 ; Hajjar et al, 2016 ; Pase et al, 2016a ; Tsao et al, 2016 ; Kim et al, 2017 ; Nilsson et al, 2017 ; Cui et al, 2018 ; Rouch et al, 2018 ; Araghi et al, 2019 ; Menezes et al, 2019 ) ( Supplementary Tables 1 , 2 ). Only the study of Zijlstra et al measured aortic PWV using MRI and showed median PWV of 9.6 m/s (interquartile range: 7.8–13.0) (Zijlstra et al, 2020 ).…”

“…Six studies with 13,648 participants were included in synthesizing adjusted ORs of the highest vs. lowest category of aortic PWV to cognitive impairment (Scuteri et al, 2013 ; Zeki Al Hazzouri et al, 2013 ; Pase et al, 2016a ; Cui et al, 2018 ; Araghi et al, 2019 ; Menezes et al, 2019 ), and three studies with 4,532 participants were synthesized for adjusted ORs for dementia (Pase et al, 2016a ; Nilsson et al, 2017 ; Rouch et al, 2018 ). The pooled results showed that the highest category of aortic PWV independently increased risk of cognitive impairment (OR 1.44, 95% CI 1.124–1.845) and dementia (OR 2.1; 95% CI 1.159–3.804) than the lowest group of aortic PWV, though with moderate heterogeneity ( Figure 3 ), but no significant publication bias ( Supplementary Figure 6 ).…”

“…In longitudinal studies, 13 studies with 17,727 participants (followed up 1-15 years) suggested significant associations between aortic PWV and cognitive decline or dementia (Scuteri et al, 2007(Scuteri et al, , 2013Waldstein et al, 2008;Watson et al, 2011;Zeki Al Hazzouri et al, 2013;Watfa et al, 2015;Hajjar et al, 2016; FIGURE 1 | Flow diagram of study selection for systematic review and meta-analysis. Pase et al, 2016a;Tsao et al, 2016;Cui et al, 2018;Rouch et al, 2018;Araghi et al, 2019;Menezes et al, 2019), in which three studies included participants with complaints of memory loss (Scuteri et al, 2007(Scuteri et al, , 2013Rouch et al, 2018), whereas two studies with 5,721 participants (followed up about 4 years) (Poels et al, 2007;Nilsson et al, 2017) and one study with 135 hemodialysis participants (followed up 1 year) (Kim et al, 2017) did not find association between aortic PWV and cognitive impairment (Supplementary Table 2).…”