26 Aug 2008

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.