Apolipoprotein E genotype does not moderate the associations of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive aging in the Lothian Birth Cohort 1936

Abstract

ObjectivesIn this replication-and-extension study, we tested whether depressive symptoms, neuroticism, and allostatic load (multisystem physiological dysregulation) were related to lower baseline cognitive ability and greater subsequent cognitive decline in older adults, and whether these relationships were moderated by the E4 allele of the apolipoprotein E (APOE) gene. We also tested whether allostatic load mediated the relationships between neuroticism and cognitive outcomes.MethodsWe used data from the Lothian Birth Cohort 1936 (n at Waves 1–3: 1,028 [M age = 69.5 y]; 820 [M duration since Wave 1 = 2.98 y]; 659 [M duration since Wave 1 = 6.74 y]). We fitted latent growth curve models of general cognitive ability (modeled using five cognitive tests) with groups of APOE E4 non-carriers and carriers. In separate models, depressive symptoms, neuroticism, and allostatic load predicted baseline cognitive ability and subsequent cognitive decline. In addition, models tested whether allostatic load mediated relationships between neuroticism and cognitive outcomes.ResultsBaseline cognitive ability had small-to-moderate negative associations with depressive symptoms (β range = -0.20 to -0.17), neuroticism (β range = -0.27 to -0.23), and allostatic load (β range = -0.11 to 0.09). Greater cognitive decline was linked to baseline allostatic load (β range = -0.98 to -0.83) and depressive symptoms (β range = -1.00 to -0.88). However, APOE E4 allele possession did not moderate the relationships of depressive symptoms, neuroticism and allostatic load with cognitive ability and cognitive decline. Additionally, the associations of neuroticism with cognitive ability and cognitive decline were not mediated through allostatic load.ConclusionsOur results suggest that APOE E4 status does not moderate the relationships of depressive symptoms, neuroticism, and allostatic load with cognitive ability and cognitive decline in healthy older adults. The most notable positive finding in the current research was the strong association between allostatic load and cognitive decline.

Cortisol hypersecretion and the risk of Alzheimer’s disease: A systematic review and meta-analysis

“…One proposed mechanism is that chronic hypercortisolism may trigger neuronal loss in the hippocampus (Lupien et al, 1998), which may in turn exacerbate cortisol hypersecretion via reduced inhibitory control of the HPA axis (Jacobson and Sapolsky., 1991;Vitale et al, 2013). In addition, cortisol levels are known to be elevated in chronic stress paradigms that have been implicated as a potential risk factor for AD (Lucassen et al, 2014); thus hypercortisolism may mediate the effects of stress and allostatic load on AD risk (Aznar and Knudsen, 2011;Crook et al, 2018). In fact, the moderate increase of cortisol in AD patients as synthesised in our study was lower than that was induced by acute stress or immunosuppression (Smith et al, 2012), and more similar to the chronic response to mild stress (Pan et al, 2018;Wust et al, 2000).…”

Allostatic Load and Its Impact on Health: A Systematic Review

“…Allostatic load was associated with a decline in cogni tive and physical functioning in older adults [16,17,130,[132][133][134][135], changes in brain structure with aging [136], brainpredicted age difference [137], and inversely relat ed to whitematter and brain volume [138]. A potential link between an immune risk phenotype and allostatic load in very old adults was identified [139].…”

The Big Five personality traits and allostatic load in middle to older adulthood: A systematic review and meta-analysis

“…This process left 12 published articles, one dissertation, and one conference proceeding that appeared to meet eligibility criteria for synthesis. However, nine of the reports used overlapping datasets: UK's Understanding Society (Barry et al, 2021;Gallagher et al, 2021); Copenhagen Aging and Midlife Biobank (CAMB; Christensen et al, 2019a;Christensen et al, 2019b);the Lothian Birth Cohort 1936 (LBC;Crook et al, 2018;Lewis et al, 2018); Midlife in the United States (MIDUS; Milad & Bogg, 2020;Turiano et al, 2015;Van Dyke et al, 2020). In four of these cases, priority was given to the report that focused on personality traits and AL, as opposed to simple adjustment for personality traits (Barry et al, 2021;Christensen et al, 2019a;Lewis et al, 2018;Van Dyke et al, 2020).…”

“…Prior to calculating z scores, some studies log transformed at least a portion of the included biomarkers to normalize their distributions. Specifically, Crook et al (2018) log transformed CRP, fibrinogen, HbA1c, triglycerides, BMI, SBP, and DBP. Milad and Bogg (2020) log transformed CRP, IL-6, glycosylated hemoglobin, fasting glucose, insulin resistance, and triglycerides.…”

“…Furthermore, some studies selected risk category cut-offs based on sex-specific z scores for some biomarkers (e.g., waist circumference; Gallagher et al, 2021;Hawkley et al, 2011;Kobrosly, 2012) or all biomarkers (Christensen et al, 2018). Half of the studies did not note whether risk cut-offs were based on sex-specific z scores (Christensen et al, 2019b;Crook et al, 2018;Luo et al, 2022;Milad & Bogg, 2020;Stephan et al, 2016).…”