Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients

Dickson O Adedeji; Jasper Holleman; Robert-Paul Juster; Chinedu T Udeh-Momoh; Ingemar Kåreholt; Göran Hagman; Malin Aspö; Sofia Adagunodo; Krister Håkansson; Miia Kivipelto; Alina Solomon; Shireen Sindi

doi:10.1016/j.bbih.2023.100592

Longitudinal study of Alzheimer's disease biomarkers, allostatic load, and cognition among memory clinic patients

Brain Behav Immun Health. 2023 Feb 1:28:100592. doi: 10.1016/j.bbih.2023.100592. eCollection 2023 Mar.

Authors

Dickson O Adedeji^{1

2}, Jasper Holleman², Robert-Paul Juster³, Chinedu T Udeh-Momoh^{2

4}, Ingemar Kåreholt^{2

5

6}, Göran Hagman^{2

7}, Malin Aspö^{2

7}, Sofia Adagunodo⁸, Krister Håkansson², Miia Kivipelto^{2

4

7

9}, Alina Solomon^{2

4

7

10}, Shireen Sindi^{2

4}

Affiliations

¹ Psychiatric Clinic, Vrinnevi Hospital, Norrköping, Sweden.
² Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.
³ Department of Psychiatry and Addiction, University of Montreal, Canada.
⁴ Ageing Epidemiology Research Unit (AGE), School of Public Health, Faculty of Medicine, Imperial College London, UK.
⁵ Institute of Gerontology, School of Health and Welfare, Aging Research Network - Jönköping (ARN-J), Jönköping University, Jönköping, Sweden.
⁶ Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
⁷ Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden.
⁸ Memory Clinic Zentralschweiz, Luzerner Psychiatrie, Lucerne, Switzerland.
⁹ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
¹⁰ Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: AD biomarkers; Allostatic load; Chronic stress; Cognition; Memory clinic.