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Thursday, November 06, 2014

Does Midlife Personality Increase AD Risk in Women?

Dear Readers,

There is an abundant amount of literature about stress and its relation to cognitive decline and Alzheimer’s Disease – with most results suggesting that perceived stress over time is detrimental to cognitive health. Knowing this, the next question often is –“Is stress and one’s reaction to stressful situations the determinant or is it “personality type” that leads to the cognitive decline and eventual dementia? A recent paper by Johansson and colleagues in the American Academy of Neurology sought to examine the role of personality in midlife to late life dementia examining data from a well established longitudinal study of women in Gothenburg, Sweden.

The Prospective Population Study of Women in Gothenburg, initiated in 1968 in Sweden, is a cohort study of 800 women who were born in 1914, 1918, 1922 and 1930. The cohort was made up of 111 women aged 38 years, 309 women aged 46 years and 290 women aged 50 years. A total of 677 (85%) participated in the first follow up cycle, with subsequent follow up rates ranging from 87% to 67% over the years (decreased rates were noted due to losses, mainly due to death. A screening phase occurred in 1968 with administration of two inventories: Eysenck Personality Inventory – an inventory that measures personality dimensions of neuroticism stability and extraversion/introversion traits that were assessed with yes /no (dichotomous) answers. The neuroticism scale assesses emotional reactivity, anxiety and psycho-somatic concerns, guilt proneness and ego strength, while the extraversion scales assessed the positive effect and sociability of the participants. Other types of assessments performed in this cohort during their study visits included a dementia assessment with the use of data from neuropsychiatric examinations, information interviews, medical records and the hospital discharge records(if available).

Self reported distress was assessed at the examinations conducted in 1968, 1974, 1980, 2000 and 2005. Typical questions asked were: “Have you experienced any period of stress (one month or longer) in relation to circumstances in everyday life, such as work, health or family situation?" Stress was defined as irritability, tension, nervousness, fear, anxiety or sleep disturbances. Ratings were based on a scale of 0 to 5, with 0 = have never experienced any period of stress to 5 = have experienced constant stress during the last five years.

The entire cohort of 800 people were followed from 1986 to 2006 and during that time, 19% of the women developed dementia, 104 developed AD, 35 developed vascular dementia and 14 developed other dementia. The mean time between baseline examinations in 1968 to dementia was 29 years and the mean age of dementia onset was 78 years. Higher scores of neuroticism were associated with increased risk of AD dementia, but not with all types of dementias or vascular dementia. Even after controlling for APOe4 allele status in a subsample of 306 women, these findings did not change.

Further AD dementia was two times higher for the women with the highest levels of neuroticism compared to those with lower levels. Longstanding distress appeared to weaken the association between neuroticism and AD dementia, whereas extraversion was not associated with risk of developing dementias. Women with high neuroticism / low extraversion had an increased risk of developing AD dementia, compared to women with low neuroticism and high extraversion in the aged adjusted models.

What do these findings mean for women? Two takeaways can be gleaned from this report. First, the association between neuroticism and AD dementias diminishes after adjusting for longstanding distress, suggesting that the association between AD dementia and neuroticism is at least partially mediated by a lifelong proneness to experience everyday life stressors in a negative way as well as stressor-related situations. Efforts to reduce stress could be beneficial to the cognitive health and prevention of the development of dementia and Alzheimer’s disease.

Second, the combination of low extraversion/high neuroticism had the highest risk of AD – as noted in other studies - and suggests that certain early and midlife personality traits could put one at risk of developing cognitive decline and dementia later in life. Some studies have shown that personality may influence the individual’s risk of dementia perhaps through poor behavioral and lifestyle choices. Other studies have suggested that people with low neuroticism more often have lifestyles with healthier metabolic, cardiovascular and inflammatory risk profiles. Biomarker studies are now reporting changes in structural imaging findings associated with neuroticism/stress, in that high levels of glucocorticoids (as seen in people who are stressed) have detrimental effects on hippocampal size, and increased numbers of tangles in the brain have been noted in people with high levels of neuroticism.

More research is needed to conduct intervention studies focusing on the role of modifying behaviors in women with these types of characteristics. Practically from a physician point of view - a discussion with women patients on how personality/behavior impacts health and wellness and how positive lifestyle changes can impact cognitive functioning in late life, is critically important.
Want to read more? Here are 3 articles you can refer to and learn more about personality and Alzheimer’s Disease in Women.

Johansson L, Guo X, Duberstein PR et al. Midlife Personality and Risk of Alzheimer’s Disease and Distress: 38 year follow up. Neurology 2014: 83: 1538-1544

Kendler KS, Gardner CO, Prescott CA. Personality and the experience of environmental adversity. Psychol Med 2003: 33: 1193-1202

Terracciano A, Iacono D, O’Brien RJ, et al Personality and resilience to Alzheimer’s Disease neuropathology: a prospective autopsy study. Neurobiol Aging 2013-:34: 1045-1050

Thanks for reading.

Neelum T. Aggarwal, MD
Steering Committee Member, ADCS
Site Principal Investigator ( RUSH) - ADCS
Rush Alzheimer’s Disease Center
Chicago, IL

Author: Neelum Aggarwal MD at 9:15 AM 0 Comments

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The Alzheimer's Disease Cooperative Study (ADCS) was formed in 1991 as a cooperative agreement between the National Institute on Aging (NIA) and the University of California, San Diego. The ADCS is a major initiative for Alzheimer's disease (AD) clinical studies in the Federal government, addressing treatments for both cognitive and behavioral symptoms. This is part of the NIA Division of Neuroscience's effort to facilitate the discovery, development and testing of new drugs for the treatment of AD and also is part of the Alzheimer's Disease Prevention Initiative.

The ADCS was developed in response to a perceived need to advance research in the development of drugs that might be useful for treating patients with Alzheimer's disease (AD), particularly drugs that might not be developed by industry.