Scientists from the Karolinska Institute published a study “Stress, depression, and risk of dementia–a cohort study in the total population between 18 and 65 years old in Region Stockholm” in Alzheimer’s Research & Therapy that addresses possible associations between chronic stress, mild cognitive impairment, and Alzheimer’s disease. The study shows how people aged between 18 and 65 with a previous diagnosis of chronic stress and depression were more likely than other people to be diagnosed with mild cognitive impairment or Alzheimer’s disease.

About 160,000 people have some form of dementia in Sweden, Alzheimer’s disease being the most common, a figure that is rising with our life expectancy. At the same time, many new diagnostic methods and early-intervention therapies have been developed in recent years, which foregrounds the need to identify more risk factors for the disease.

Previous studies have demonstrated a possible association between chronic stress, depression, and dementia. This present study now shows that people who have been diagnosed with chronic stress or depression are more likely to be diagnosed with Alzheimer’s disease.

Alzheimer’s risk more than twice as high

This study shows that the risk of Alzheimer’s disease was more than twice as high in patients with chronic stress and in patients with depression as it was in patients without either condition; in patients with both chronic stress and depression it was up to four times as high.

The risk of developing cognitive impairment was elevated about as much. A patient is deemed to be suffering chronic stress when he or she has been under stress with no opportunity for recuperation for at least six months.

“Chronic stress and depression are potential risk factors for mild cognitive impairment and dementia, including Alzheimer disease. The aim was to investigate whether any such risk is additive,” write the investigators.

“Cohort study including 1 362 548 people (665 997 women, 696 551 men) with records in the Region Stockholm administrative healthcare database (VAL).

Exposure was a recorded ICD-10 diagnosis of chronic stress, depression, or both, recorded in 2012 or 2013. Outcome was a diagnosis of Alzheimer disease, other dementia, or mild cognitive impairment recorded from 2014 through 2022. Odds ratios with 99% confidence intervals (CI) adjusted for age, sex, neighborhood socioeconomic status, diabetes, and cardiovascular disorders were calculated.

“During the exposure period, 4 346 patients were diagnosed with chronic stress, 40 101 with depression, and 1 898 with both. The average age at baseline was around 40 years in all groups. In the fully adjusted model, the odds ratio of Alzheimer disease was 2.45 (99% CI 1.22–4.91) in patients with chronic stress, 2.32 (99% CI 1.85–2.90) in patients with depression, and 4.00 (99% CI 1.67–9.58) in patients with chronic stress and depression.

“The odds ratio of mild cognitive impairment was 1.87 (99% CI 1.20–2.91) in patients with chronic stress, 2.85 (99% CI 2.53–3.22) in patients with depression, and 3.87 (99% CI 2.39–6.27) in patients with both. When other dementia was analyzed, the odds ratio was significant only in patients with depression, 2.39 (99% CI 1.92–2.96).

“Documented chronic stress increased the risk of mild cognitive impairment and Alzheimer disease. The same was seen with depression. The novel finding is the potential additive effect of chronic stress to depression, on risk of MCI and AD.”

Causality is still unknown

“The risk is still small, and the causality is unknown,” says the study’s last author Axel C. Carlsson, PhD, docent at the department of neurobiology, care sciences, and society. “That said, the finding is important in that it enables us to improve preventative efforts and understand links with the other risk factors for dementia.”

The study was conducted using Region Stockholm’s administrative healthcare database, which contains all healthcare contacts compensated by the region. The researchers focused on patients between the ages of 18 and 65 and between 2012 and 2013. They identified 44,447 people with a diagnosis of chronic stress and/or depression and followed them for eight years to see how many of them were later diagnosed with mild cognitive impairment or Alzheimer’s disease.

A comparison with all other 1,362,548 individuals in the age bracket showed that more people with chronic stress or depression had also been diagnosed with mild cognitive impairment or Alzheimer’s disease.

“It’s uncommon for people in this age group to develop dementia, so we need to identify all possible risk factors for the disease,” says Carlsson. “We show here that the diagnosis is more common in people who have suffered chronic stress or depression, but more studies will be required if we’re to demonstrate any causality there.”

The researchers will now be continuing their work and developing questionnaires and cognitive tests to aid the early identification of people at risk of dementia.



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