Allostatic load (AL) is defined as the cumulative dysregulation of neuroendocrine, immunological, metabolic, and cardiovascular systems that increases the susceptibility to stress-related health ...problems. Several dementia and Alzheimer's disease (AD) risk factors have been identified, yet little is known about the role of AL and its associations with AD biomarkers (e.g., beta-amyloid (Aβ) or tau) and cognitive function among memory clinic patients. Hence, this study aims to assess the association between AL and AD biomarkers, cognitive performance, and cognitive decline after 3-years of follow-up.
Data from 188 memory clinic patients were derived from the Cortisol and Stress in AD (Co-STAR) study in Sweden. Participants underwent baseline assessments including blood tests for AL measures (including cortisol, thyroid stimulating hormone, cobalamin, homocysteine, leukocytes, glycated hemoglobin, albumin, high-density and low-density lipoprotein cholesterol, triglycerides, and creatinine), cerebrospinal fluid (CSF) sampling for AD biomarkers and neuropsychological tests including five cognitive domains. Linear regressions were conducted, adjusting for age, sex, and education.
Higher AL was associated with lower CSF Aβ1-42 levels (β = −0.175, p = 0.025), reflecting higher brain levels of Aβ1-42. Stratified analyses suggested a significant association among women but not men, although the AL-sex interaction was not statistically significant. AL was not significantly associated with T-tau level (β = −0.030, p = 0.682) and P-tau level (β = 0.091, p = 0.980). There were no significant associations between AL and cognition or cognitive decline after 3 years.
This study showed that higher AL was associated with increased brain amyloid accumulation. This suggests that AL may play a role in AD/dementia pathophysiology. Potential sex-related differences should be assessed in further larger studies.
ObjectiveThis study aims to investigate the relationship between diurnal cortisol patterns, cognition and Alzheimer’s disease (AD) biomarkers in memory clinic patients.MethodMemory clinic patients ...were recruited from Karolinska University Hospital in Sweden (n=155). Diurnal cortisol patterns were assessed using five measures: awakening levels, cortisol awakening response, bedtime levels, the ratio of awakening to bedtime levels (AM/PM ratio) and total daily output. Cognition was measured in five domains: memory, working memory, processing speed, perceptual reasoning and overall cognition. AD biomarkers Aβ42, total tau and phosphorylated tau were assessed from cerebrospinal fluid (CSF). Cognition was measured at follow-up (average 32 months) in a subsample of participants (n=57).ResultsIn assessing the associations between cortisol and cognition, higher awakening cortisol levels were associated with greater processing speed at baseline. No relationship was found between diurnal cortisol patterns and change in cognition over time or CSF AD biomarkers in the total sample. After stratification by CSF Aβ42 levels, higher awakening cortisol levels were associated with worse memory performance in amyloid-positive participants. In amyloid-negative participants, higher bedtime cortisol levels and a lower AM/PM ratio were associated with lower overall cognition, greater awakening cortisol levels were associated with better processing speed, and a higher AM/PM ratio was associated with better perceptual reasoning. Additionally, higher awakening cortisol levels were associated with lower CSF Aβ42 levels in amyloid-positive participants, while higher bedtime cortisol levels and a lower AM/PM ratio were associated with higher CSF total tau in amyloid-negative participants.ConclusionsOur findings suggest that diurnal cortisol patterns are associated with cognitive function and provide new insights into the association between diurnal cortisol patterns and AD-related CSF biomarkers. Further research is needed to examine the complex relationship between cortisol, cognition and brain pathology.
Background
Chronic stress has been studied as a potential lifestyle risk factor for Alzheimer's disease (AD). Prolonged stress can lead to alterations in diurnal patterns of cortisol. This study aims ...to investigate the relationship between diurnal cortisol patterns, cognition, and AD biomarkers in memory clinic patients.
Method
Participants diagnosed with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), or AD dementia were recruited from Karolinska University Hospital memory clinic in Sweden (n=155). Baseline cognition was measured using five cognitive domains (memory, working memory, processing speed, perceptual reasoning, overall cognition), operationalized as average z‐scores. Diurnal cortisol patterns were assessed using five salivary cortisol measures: awakening levels, cortisol awakening response, bedtime levels, the ratio of awakening to bedtime cortisol levels (AM/PM ratio), and total daily output. AD biomarkers Aβ42, total tau (T‐Tau), and phosphorylated tau (P‐Tau) were measured from cerebrospinal fluid. Cognition was measured at follow‐up (average 32 months) in a subsample of participants (n=57).
Result
Awakening cortisol levels were significantly higher in AD dementia compared with SCI. Greater cortisol awakening response was associated with better memory performance (OR= 1.57, 95% CI: 1.10 – 2.23), while a greater AM/PM ratio (OR= 2.21, 95% CI: 1.15 – 4.25) and lower bedtime cortisol levels (OR= .64, 95% CI: .40 – 1.01) were associated with better overall cognition. Cortisol measures were not associated with cognitive decline during follow‐up or with AD biomarkers in the full sample. However, in stratified analyses, higher awakening cortisol levels were associated with lower CSF Aβ42 in amyloid‐positive participants (b= ‐60.13; 95% CI ‐102.73 ‐ ‐17.52), while higher bedtime cortisol levels (b= .09; 95% CI .02 ‐ .17) and a lower AM/PM ratio (b= ‐.12; 95% CI ‐.23 ‐ ‐.02) were associated with higher CSF T‐Tau in amyloid‐negative participants.
Conclusion
This study shows that diurnal cortisol patterns are associated with cognitive performance in memory clinic patients. In people without amyloid pathology, cortisol may affect cognition through neurodegeneration‐related mechanisms, leading to the observed correlation with T‐Tau. Meanwhile, in amyloid‐positive participants, the greater pathology level may affect cortisol patterns. Further research should investigate the complex relationship between cortisol, cognition, and brain pathology.
