Abstract
Studies exploring the simultaneous influence of several physiological and environmental factors on domain-specific cognition in late middle-age remain scarce. Therefore, our objective was to determine the respective contribution of modifiable risk/protective factors (cognitive reserve and allostatic load) on specific cognitive domains (episodic memory, executive functions, and attention), taking into account non-modifiable factors [sex, age, and genetic risk for Alzheimer’s disease (AD)] and AD-related biomarker amount (amyloid-beta and tau/neuroinflammation) in a healthy late-middle-aged population. One hundred and one healthy participants (59.4 ± 5 years; 68 women) were evaluated for episodic memory, executive and attentional functioning via neuropsychological test battery. Cognitive reserve was determined by the National Adult Reading Test. The allostatic load consisted of measures of lipid metabolism and sympathetic nervous system functioning. The amyloid-beta level was assessed using positron emission tomography in all participants, whereas tau/neuroinflammation positron emission tomography scans and apolipoprotein E genotype were available for 58 participants. Higher cognitive reserve was the main correlate of better cognitive performance across all domains. Moreover, age was negatively associated with attentional functioning, whereas sex was a significant predictor for episodic memory, with women having better performance than men. Finally, our results did not show clear significant associations between performance over any cognitive domain and apolipoprotein E genotype and AD biomarkers. This suggests that domain-specific cognition in late healthy midlife is mainly determined by a combination of modifiable (cognitive reserve) and non-modifiable factors (sex and age) rather than by AD biomarkers and genetic risk for AD.
Highlights
The constant increase in life expectancy is associated with an increase in age-related physical and cognitive dysfunctions (WHO, 2011)
Based on previous findings showing that the interaction between Aβ and tau may be even more important for cognitive performance than their unilateral effect (Hanseeuw et al, 2019), we explored this type of interaction in models having apolipoprotein E (APOE) and both Alzheimer’s disease (AD) biomarkers (N = 58)
This study investigated whether performance assessed over episodic memory, executive and attentional domains in healthy late-middle-aged individuals is associated with a combination of risk/protective factors
Summary
The constant increase in life expectancy is associated with an increase in age-related physical and cognitive dysfunctions (WHO, 2011). Deposits of amyloid-beta (Aβ) and tau protein, two main biomarkers of AD pathophysiology, are observed decades before the first clinical signs of cognitive decline (Jack and Holtzman, 2013). The presence of these biomarkers does not, mean that people will necessarily develop clinical AD; they are only indicative of an increased risk for developing the disease (Dumurgier et al, 2017; Roe et al, 2018). Besides Aβ and tau proteins (Betthauser et al, 2019), several physiological and psychological environmental protective and risk factors were proposed to explain this variability (Norton et al, 2014; Livingston et al, 2017), such as cognitive reserve (Cabeza et al, 2018; Stern et al, 2018), allostatic load (Karlamangla et al, 2014), and genetics, with ε4 polymorphism in apolipoprotein E (APOE) gene (Greenwood et al, 2014)
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