Neuroticism Linked to Higher Dementia Risk

Pauline Anderson

October 01, 2014

A high degree of neuroticism—being easily worried, anxious and stressed, and developing psychosomatic symptoms such as headache and sleep problems—in midlife is associated with an increased incidence of late-life Alzheimer's disease (AD), a new study suggests.

This association was diminished after adjustment for long-standing distress, suggesting that being prone to everyday life stressors at least partly explains the relationship between AD and neuroticism.

What sets this new study apart from previous work linking AD with neuroticism is that it followed a group of women for almost 40 years, the researchers say.

"Before, we knew that Alzheimer's disease patients had a higher degree of neuroticism, but that could have been a symptom of the disease; when you're diagnosed with Alzheimer's, it's normal to become worried and easily stressed," said lead author Lena Johansson, PhD, Neuropsychiatric Epidemiology Unit, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden.

But this new study showed that rather than being a result of dementia, neuroticism "is more of a risk factor" for AD, said Dr Johansson.

Dr. Lena Johansson

Their results are published online October 1 in Neurology.

Personality Dimensions

The study included 800 women, mean age 46 years at study outset (1968), who were followed until 2006. At baseline, researchers measured personality dimensions of participants using the Eysenck Personality Inventory. The neuroticism scale assesses emotional reactivity, anxiety and psychosomatic concerns, ego strength, and guilt proneness. The extroversion scale assesses sociability and positive affect.

Also at baseline, and then at various time points, participants were asked about distress related to circumstances of everyday life, such as work, health, or family situations. Responses were categorized on a scale ranging from 0 to 5, from never experiencing stress to experiencing constant stress, over the last 5 years.

Diagnoses of dementia were based on neuropsychiatric evaluations, interviews, medical records, and the Swedish Hospital Discharge Register, and were compatible with Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria.

During the study, 19% of the women were diagnosed with dementia, most (104 of 153) with AD. The mean age at dementia onset was 78 years.

The mean value for neuroticism was 8.1 and the mean value for extraversion was 11.3. Scores for these two personality traits were significantly correlated (P = .001).

Higher scores for neuroticism were associated with increased risk for AD dementia (hazard ratio [HR] per point increase in score, 1.04; 95% confidence interval [CI], 1.00 - 1.08; P = .046), after adjustment for age, education, hypertension, coronary heart disease, smoking, body mass index, and depression), but not for all-type dementia or vascular dementia.

This association was similar after exclusion of AD dementia diagnosed before 1992 and remained after controlling for APOE status in a subsample of 306 women.

In terms of quartiles, the risk for AD dementia was two-fold higher for the highest vs lowest scorers for neuroticism (HR, 1.99; 95% CI, 1.00 - 4.00; P = .050).

When researchers also adjusted for long-standing distress, the association was no longer significant, but distress was significantly associated with increased risk for AD dementia.

These results, said Dr Johansson, imply that women with a high degree of neuroticism have more risk of developing AD if they also have a high level of distress.

"That can mean that it's the stress that's the main risk," she said. "We don't get the whole picture from this study and so it's difficult to say, but that's our hypothesis."

If that's the case, some women who learn ways to cope with stress could lessen their risk for AD dementia. While it may not be possible to change personality, research shows that some interventions — for example, yoga and meditation — may ease stress.

"We need more intervention studies" to determine exactly what approaches work best to mitigate the AD risk, said Dr Johansson.

In general, women under significant and long-standing stress (eg, if they have trouble sleeping and suffer daily headaches) should get advice from their doctor on changing their lifestyle, said Dr Johansson.

Extraversion Role

Although extraversion alone had no effect on AD risk, when researchers combined both personality scales, the women with high neuroticism and low extraversion had the highest risk for AD dementia (HR of 2.50 after adjustment for age) compared with those who had low neuroticism and high extraversion.

However, after further adjustment for social and medical covariates, the association was no longer significant.

Women with high neuroticism and high extraversion or low neuroticism and low extraversion had no increased risk for AD dementia in any of the models.

Although the study enrolled only women, Dr Johansson said she has no reason to believe that the results would be different in men.

According to the authors, both neuroticism and stress have been linked to functional and structural changes in the hippocampus. Neuroticism has also been associated with an increased amount of neurofibrillary tangles in the brain.

People with a high degree of neuroticism may also have unhealthy metabolic, cardiovascular, and inflammatory risk profiles. The fact that neuroticism has been associated with cardiovascular disease might help explain the association between this personality trait and AD, said the authors.

Because of the study's length, the findings are probably not due to early AD pathology and also are not likely caused by selective survival because stress and early cognitive decline both probably predict mortality and so obscure the association between neuroticism and AD, according to an accompanying editorial.

Robert Stewart, MD, King's College, Institute of Psychiatry, London, United Kingdom, points out in his editorial that the findings of this and other studies "are consistent with a broader truth that people who are more exposed (or more vulnerable) to the vicissitudes of life may also be less likely to age 'well,' whether this is measured by mortality, cardiovascular disease, AD, or other aging-related outcomes."

A deficiency of such research into age-related disorders, Dr Stewart writes, is a tendency to focus on individual risk factors and outcomes.

"The substrates for accelerated aging remain tantalizingly elusive but worth pursuing. In particular, they may usefully take AD beyond the single-disorder paradigm, which is proving less than useful for intervention development."

Pieces of Evidence

Approached for comment, Dean M. Hartley, PhD, director, Science Initiatives, Alzheimer's Association, said the study provides "one of the many pieces" of new evidence suggesting that personality may have something to do with the development of AD.

The study has several strengths, including its large cohort, longitudinal nature, and lengthy follow-up, but it also has some "issues," said Dr Hartley.

For one thing, distress was measured with a single question and was self-reported. "It's difficult to say if a person is reporting distress over the past 5 years or if it's reflective of what that person remembers a couple of weeks ago," said Dr Hartley.

As well as focusing just on women, the study included only Swedish participants, who are from a fairly homogenous population in terms of lifestyle and genetics, noted Dr Hartley.

He would like to see trials use more objective measures of stress, such as biochemical tests and structural brain imaging. "There are ways to measure stressors biochemically, so not just in terms of what you think is a stressor but actual changes, for example, oxidation, in the body."

He would also like to see investigations into the contribution of potential AD risk factors over the whole life span, not just from middle age.

He stressed that AD is a now considered "a continuum," with new evidence suggesting that the disease may start 20 years before the onset of clinical symptoms. If that's the case, whether personality is driving the disease "is still a little bit of a question," said Dr Hartley. "Neuroticism and AD may go hand in hand."

It's possible, he added, that genes drive both neuroticism and AD. "They may run parallel as opposed to one causing the other."

The Alzheimer's Association has funded some researchers involved in the study. Dr Johansson has disclosed no relevant financial relationships. Dr Stewart has received research funding from Pfizer, Lundbeck, J&J, and Roche.

Neurology. Published online October 1, 2014. Abstract Editorial

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