CV risk factors early in life associated with worse midlife cognitive performance

21-6-2017 • Rovio SP et al, JACC 2017

Cardiovascular Risk Factors From Childhood and Midlife Cognitive Performance
The Young Finns Study

Rovio SP, Pahkala K, Nevalainen J, et al.
J Am Coll Cardiol 2017;69:227989

Introduction and methods

Epidemiological and experimental data suggest that midlife high BP, abnormal serum lipids, and smoking, are associated with cognitive decline later in life [1,2]. More recently, the CARDIA study showed that there is a link between cumulative burden of young adulthood CV risk factors and cognitive performance in young and middle-aged adults [3].
Potential pathophysiologic mechanisms have been examined in this context, like for example:
  • Damage of neuronal and vascular tissues of the brain by CV risk factors [4].
  • Influence of the expression of genes in the brain that are relevant for cellular mechanisms regarding learning memory [5].
In this analysis of the Young Finns Study, the associations between childhood and adolescence CV risk factors and midlife cognitive performance was evaluated, in a population-based cohort that was followed-up for 31 years in 3- to 9-year intervals. In all follow-up visits, BP, serum lipids, BMI, and smoking were assessed, and the cumulative exposure for each risk factor was determined in childhood (6 – 12 years), adolescence (12 – 18 years) and young adulthood (18 to 24 years).
Cognitive testing was performed in 2,026 participants aged 34 to 49 years, using a computerized cognitive testing battery focusing on cognitive domains that are mostly affected in the early stages of cognitive decline.

Main results

  • Elevated SBP, high total- or LDL-C, and cigarette smoking in childhood, adolescence, and young adulthood, were consistently associated with lower midlife visual and episodic memory and visuospatial associative learning (PAL test).
  • The results for the PAL test remained consistently unchanged after further adjustments for family income, blood-pressure and lipid-lowering medication, and history of CV diseases or DM.
  • There was a 0.42 SD difference between the extreme SBP quartiles, meaning that compared with the lowest quartile, individuals in the highest quartile of cumulative SBP exposure were 8.4 years older in terms of cognitive function.
  • Similarly, there was a 0.33 SD difference between the extreme serum total-C quartiles, corresponding to 6.6 years of premature aging of cognitive function in the highest quartile, compared with the lowest quartile.
  • In the unadjusted bivariate analyses, early life exposure to elevated SBP, serum total-C, and smoking were inversely related and independently associated with the PAL test performance.
  • In further multivariate analyses including childhood academic performance, adulthood education, apoEε4 genotype, and adulthood physical activity level, the results for BP and serum total-C remained essentially similar for visual and episodic memory and visuospatial associative learning (PAL test: n = 1,450; SBP: β = –0.065; SE = 0.031; P = 0.034; serum total-C: β = –0.076; SE = 0.028; P = 0.006).
  • The corresponding results for smoking were: 0.17 SD difference between smokers and non-smokers (3.4 years). Additional adjustments diluted the effects of smoking for visual and episodic memory and visuospatial associative learning (PAL test: n = 1,450; smoking: β = –0.032; SE = 0.060; P = 0.60) and for recognition, visual processing, and sustained attention (RVP test: n = 1,545; smoking: β = –0.033, SE = 0.057; P = 0.568). The covariate that was mainly responsible for the dilution of the effect of smoking was childhood academic performance, which was directly and highly significantly (P value always <0.008) associated with all midlife cognitive domains.
  • Persons with none or 1 risk factor during their early life (ages 6 to 24 years) performed better in the PAL test compared with participants with 2 to 3 early life CV risk factors. After adjustment, the association between the number of early life CV risk factors and midlife cognitive performance was highly significant (n = 1,733; β = –0.135, SE = 0.034; P < 0.0001).


In a population-based cohort that was followed-up for 31 years, the cumulative burden of BP, serum total- and LDL-C, and smoking from childhood and adolescence, were independently associated and combined with midlife cognitive performance. These findings support the implementation of primordial strategies to prevent CV risk factors from childhood, in order to promote cognitive health in adulthood.

Editorial comment [6]

In their editorial article, Lloyd-Jones and Allen start with a clear positioning of an unmet medical need: ‘It is increasingly being recognized that loss of ideal cardiovascular health and exposure to elevated cardiovascular risk factor levels at young ages, and the accumulated burden of these risk factors, is a major contributor to health outcomes in later life. In fact, the top global research priorities for the next decade in dementia research call for a focus on prevention; however, until recently, it has been unclear at what ages this accumulated burden starts to accrue and when prevention efforts should begin.’
In this context, they summarize the study of Rovio et al, and focus on one important weakness. A single measure of cognitive performance was used in the study, leaving open the chicken-or-egg question: Are CV risk factors leading to limited cognitive function, or was the limited cognitive function already there during childhood, leading to unhealthy behaviors? A longitudinal analysis in the future might answer this question. For the time being, the authors of the editorial conclude: ‘Rovio et al show compelling data on how influential very early life exposures are on long-term health. They highlight how crucial it is to focus our efforts on primordial prevention in childhood so we can help current and future generations remain in both ideal cardiovascular and cognitive health.’
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1. Knopman D, Boland LL, Mosley T, et al. Cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology 2001;56:42–8.
2. Tolppanen A-M, Solomon A, Soininen H, et al. Midlife vascular risk factors and Alzheimer’s disease: evidence from epidemiological studies. J Alzheimers Dis 2012;32:531–40.
3. Yaffe K, Vittinghoff E, Pletcher MJ, et al. Early adult to midlife cardiovascular risk factors and cognitive function. Circulation 2014;129:1560–7.
4. Ueno M, Sakamoto H, Tomimoto H, et al. Blood-brain barrier is impaired in the hippocampus of young adult spontaneously hypertensive rats. Acta Neuropathol 2004;107:532–8.
5. Mateos L, Akterin S, Gil-Bea F-J, et al. Activity regulated cytoskeleton-associated protein in rodent brain is down-regulated by high fat diet in vivo and by 27-hydroxycholesterol in vitro. Brain Pathol 2009;19:69–80.
6. Lloyd-Jones D, Allen NB. Childhood Cardiovascular Risk Factors and Midlife Cognitive Performance. Time to Act on Primordial Prevention. J Am Coll Cardiol 2017;69:2290-2.

adolescenceblood pressurechildhoodCognitivecognitive functionhypertensionLDLmidlifeSBPsmoking

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