The newest potential protective factor for Alzheimer’s might be wrapped around your ring finger. So suggests a prospective, population-based study presented last month at the International Conference on Alzheimer’s Disease (ICAD) in Chicago. Having analyzed data on more than 1,400 people from eastern Finland, Krister Håkansson of Växjö University and Karolinska Institutet, Växjö, and Stockholm, Sweden, reported that those who were married or living with a significant other in mid-life had a 50 percent lower risk of developing late-life dementia compared to those living alone. Taking a closer look at subgroups who maintained their solo-dwelling status over at least two decades, Håkansson found that singles and divorcées had a two- to threefold higher risk of dementia relative to the marrieds, whereas widows were more than six times as likely to develop AD. Among widows carrying the AD genetic risk factor ApoE4, the frequency of AD cases shot up to roughly 14-fold relative to non-ApoE4 carriers living together. In providing hard numbers to suggest that getting hitched and staying together has long-term brain benefits, this study supports the general hypothesis that social engagement may help people compensate for neurodegeneration seen with AD and related diseases.

Twin studies have placed AD heritability estimates between 60 and 80 percent, with the remaining variance stemming from environmental influences (Gatz et al., 2006). Among such non-genetic risk factors is an active social life (see ARF related news story). This generally means higher participation in activities that involve physical or mental exercise, factors that protect against AD in people (Teri et al., 2003) and mice (see ARF related news story). In light of the broader claim that intellectual and social enrichment helps guard against age-related dementia, Håkansson had a hunch that these protective effects could be more specifically linked to mid-life marital status. “It’s hard to imagine any form of social and intellectual stimulation more intensive than couple relations,” he said.

The 1,449 participants in Håkansson’s analysis came from the population-based Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, which assessed middle-aged individuals between 1972 and 1987, and again about 21 years later, for signs of dementia. Owing to an unusually high number of male deaths from Finland’s world-leading cardiovascular mortality rate and its war with Russia during World War II, the sample included many early widows, most of whom (105/111) were still unmarried decades later.

At re-examination in 1998, 143 participants in Håkansson’s study were diagnosed with some form of cognitive impairment—among those, 82 with mild cognitive impairment (MCI) and 48 with AD. Compared to those living with a spouse or significant other at mid-life, singles had a doubled risk of late-life dementia. If those singles continued to live without a partner through follow-up 21 years later, their rate of developing cognitive impairment went up to nearly three times that of couples living together, Håkansson said. The study adjusted for other mid-life factors, including education, body mass index, cholesterol, blood pressure, occupation, physical activity, smoking habits, depression, ApoE status, gender, and age at follow-up.

A closer look at the circumstances behind singlehood yielded some intriguing findings as well. If living without a partner were regarded as a risk factor for late-life dementia, one might presume that all-life singles would be worse off than those who had been previously married. Yet Håkansson found the opposite. Middle-aged widows who remained alone into late-life were almost three times as likely as other singles—and more than six times as likely as people living with spouses or significant others—to develop Alzheimer disease. AD prevalence among widows carrying the ApoE4 allele was about 14 times higher than that of non-ApoE4 carriers living together. To Håkansson, these findings fit the socio-genetic disease model. He likened singlehood induced by losing one’s partner early in life to a traumatic event that, if sustained, seems to add to the AD risk conferred by the ApoE4 gene.—Esther Landhuis.

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  1. The demographic study of Krister Håkansson of Växjö University, Växjö, and Karolinska Institutet, Stockholm, Sweden, is very interesting. The effects of pair bonding and attachment have substantial effect on hormonal induction and neuroprotection.

    Oxytocin is a hormone that has been studied to a great extent in the recent years, from both a psychological stance—learning about attachment—and the steroidal effects oxytocin has on the brain (Carter et al., 2005, and Carter, 2007).

    Calza et al. (1997) showed that to a great extent corticotrophin-releasing hormone neurons of the paraventricular nucleus remain high in numbers in the elderly. However, the number of oxytocin neurons and vasopressin neurons decrease in the elderly. Thus, the induction of the hormone oxytocin with a rekindling of bonding and attachment is evident in the increase and maintenance of the number of oxytocin and vasopressin neurons, i.e., affecting both vascular circulation and neuroprotection from corticotrophin stress effects, which are excitotoxicity and cell death.

    The involvement of the hypothalamic-pituitary-adrenal axis in stress is greater when there is no marriage support in the widowed or bachelors. Love and attachment increase oxytocin levels and thus reduce neurodegeneration (Czlonkowska et al., 2003) given a cascade of neurohumoral protection.

    In an interdisciplinary conference, Carter (2007) delivered a talk about the effects of oxytocin, one of which was the "rewiring of the brain" after childbirth. Mother-child bonding and love affected the brain significantly. She also indicated that, generally, oxytocin reduces muscle mass. That seems to confound the mortality rate data; muscle mass is indicated in longevity and that was the finding with the Belgian Blue cow.

    There seems to be a paradox in mortality rate that is related to the effects of oxytocin's neuroprotection (increased brain mass) and that which affects muscles (reduced mass) in Alzheimer's patients or the elderly in general. These are important for demographical research.

    See also:

    Carter, C.S., Ahnert, L. Groosmann, K. E., Hardy, S. B., Lamb, M. E., Porges, S. W., et al. (Eds.).(2005). Attachment and bonding: A new synthesis. Cambridge, MA: MIT Press.

    Carter, C.A. (2007, March 30 - April 1). A Mother's Love. Presented at "Seven Dimensions of Emotion: Integrating Biological, Clinical, and Cultural Perspectives on Fear, Disgust, Empathy, Grief, Anger, Love and Hope." FPR-UCLA 3rd Interdisciplinary Conference. Korn Convovation Hall, UCLA.

    References:

    . Hormonal influences on brain ageing quality: focus on corticotropin releasing hormone-, vasopressin- and oxytocin-immunoreactive neurones in the human brain. J Neural Transm. 1997;104(10):1095-100. PubMed.

    . Sex differences in oxytocin and vasopressin: implications for autism spectrum disorders?. Behav Brain Res. 2007 Jan 10;176(1):170-86. PubMed.

    . Influence of estrogens on neurodegenerative processes. Med Sci Monit. 2003 Oct;9(10):RA247-56. PubMed.

References

News Citations

  1. Social Seniors: Strong Networks Build Cognitive Reserve
  2. Sorrento: More Fun, Less Amyloid for Transgenic Mice

Paper Citations

  1. . Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry. 2006 Feb;63(2):168-74. PubMed.
  2. . Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA. 2003 Oct 15;290(15):2015-22. PubMed.

External Citations

  1. ApoE4

Further Reading