Stress weakens cognitive reserve's protective effects in Alzheimer's patients

A study of memory clinic patients in Sweden found that individuals with higher cognitive reserve tend to have better cognitive functioning. However, physiological stress, indicated by levels of the hormone cortisol, weakened this association. The research was published in the Alzheimer’s & Dementia.

Cognitive reserve refers to the brain’s ability to adapt and find alternative ways to complete tasks despite damage or aging. This concept suggests that individuals with a higher cognitive reserve can better cope with neurological challenges due to a more robust and adaptable neural network. Factors such as education, occupation, and engaging in stimulating activities throughout one’s lifetime contribute to building cognitive reserve.

Cognitive reserve is particularly important as individuals reach advanced age, when age-related cognitive decline becomes more apparent. In this situation, people with higher cognitive reserve tend to experience a delayed onset of cognitive decline and are better able to maintain their cognitive functioning as they age. Cognitive reserve might be especially crucial for individuals suffering from conditions that lead to accelerated cognitive decline, such as Alzheimer’s disease.

Study author Manasa Shanta Yerramalla and her colleagues aimed to explore the associations between cognitive reserve and biomarkers of Alzheimer’s disease in patients at a memory clinic. They also wanted to determine whether the strength of this association is affected by stress.

Study participants were 113 patients at the memory clinic at Karolinska University Hospital, Huddinge, Sweden. They were aged 45 years and above and had their first visit to the memory clinic between 2014 and 2017. These individuals agreed to participate in the Cortisol and Stress in Alzheimer’s Disease (Co-STAR) study. On average, researchers followed them for 32 months since their inclusion in the study. Of the initial group, 43-45 provided sufficient data on cognitive functioning at the end of the study period.

During their regular visits to the hospital memory clinic, participants completed neuropsychological tests assessing four cognitive domains (memory, processing speed, working memory, and perceptual reasoning) as well as global cognition. They also underwent magnetic resonance imaging and gave samples of blood and cerebrospinal fluid. From cerebrospinal fluid, study authors derived data on biomarkers of Alzheimer’s disease – Aβ42, phosphorylated tau 181 (p-tau181), and total tau (t-tau).

Additionally, study participants received saliva sampling kits for home use, allowing researchers to assess participants’ cortisol levels. Cortisol is a steroid hormone produced by the adrenal glands that plays a crucial role in regulating the body’s stress response. Its levels are used as an indicator of stress.

The study authors created an index of participants’ cognitive reserve by combining data on their education, complexity of their occupations, quality of social connections (marital status, contact with family, friends, relatives, social network size, and social support), and participation in leisure activities (from a list of 28).

Results showed that participants with higher cognitive reserve tended to have better cognitive functioning in all domains except memory. Their scores on memory functioning were better, but the average difference between individuals with high and low cognitive reserve in memory functioning was very small, making it uncertain whether the difference was truly associated with cognitive reserve or due to random variations.

Individuals with higher cognitive reserve also reported experiencing lower stress. They tended to have more pronounced differences between cortisol levels in the morning and evening. The two groups (high and low cognitive reserve) did not differ in levels of Alzheimer’s disease biomarkers.

Further analysis revealed that stress reduced the strength of the association between cognitive reserve and cognitive functioning.

“Our findings suggest that cognitive reserve might confer neurocognitive benefits for memory clinic patients. It also appears that markers of stress dysregulation may reduce the neurocognitive advantages accumulated via cognitively stimulating and enriching experiences and late-life lifestyles in individuals with cognitive impairments,” the study authors concluded.

The study contributes to the scientific understanding of the interplay between cognitive reserve, stress, and cognitive functioning among adults in advanced age. However, it should be noted that the study used a proxy measure of cognitive reserve and that many participants dropped out during the course of the study.

The paper, “Cognitive reserve, cortisol, and Alzheimer’s disease biomarkers: A memory clinic study”, was authored by Manasa Shanta Yerramalla, Alexander Darin-Mattsson, Chinedu T Udeh-Momoh, Jasper Holleman, Ingemar Kåreholt, Malin Aspö, Göran Hagman, Miia Kivipelto, Alina Solomon, Anna Marseglia, and Shireen Sindi.