18 Sep 2017

Numerous studies have reported a dip in dementia incidence in the developed world. When did this trend begin? In the September 5 JAMA Neurology, researchers led by Carol Derby at Albert Einstein College of Medicine in New York help address this. The researchers analyzed birth cohort data from the Einstein Aging Study, which enrolls cognitively healthy older adults living in the Bronx. Surprisingly, people born after 1928 were 85 percent less likely to develop dementia than those born before that year. The reason for such a stark drop in incidence is unclear. Neither better education nor improved cardiovascular health accounted for the effect.

In one New York community, people born after 1929 were much less likely to develop dementia.

Neither cardiovascular health nor education explain the finding.

“The birth cohort effect is intriguing but will need replication in other populations,” Sudha Seshadri at Boston University wrote to Alzforum. Seshadri was not involved in the research. “This important insight compels us to search for novel social and environmental factors that may have impacted this birth cohort. Changes in nutrition, education, lead levels, other pollutants, and infections all occurred and would be worth examining in cohorts and in animal models,” Seshadri added (see full comment below).

Steady Decline. Within each age group, dementia rates are lower for people born later. [© 2017 American Medical Association. All rights reserved.]

A growing number of studies have reported a drop in dementia incidence in the U.S. and Europe over the last two or three decades (e.g., Feb 2016 news; Apr 2016 news; Nov 2016 news). Researchers have speculated that this may be due to better public health, particularly cardiovascular health (May 2013 news; Jul 2014 conference news). The finding is not uniform, however, with a handful of studies reporting higher dementia incidence that may be due to greater recognition of the disease or a larger number of people reaching old age (Mar 2017 news; May 2017 news; Abdulrahman 2014).

To try to clarify the picture, Derby and colleagues examined data from participants who enrolled in the Einstein Aging Study between 1993 and 2015. The cohort comprised 1,348 participants who had completed at least one annual follow-up visit, with an average follow-up time of four years. All participants were older than 70, and about two-thirds were non-Hispanic white. The researchers diagnosed dementia by a clinical exam, in accordance with DSM-IV criteria published in 1994. A subset of participants donated their brains after death, and 96 percent of those with a dementia diagnosis had some type of extensive brain pathology. For example, in a subgroup diagnosed with AD, 79 percent had plaques and tangles (Katz et al., 2012).

Within each age group, the researchers saw a steady drop in dementia incidence for those born in later years (see image above). Among people born before 1920 there were 5.09 cases per 100 person-years. This dropped to 3.11 for people born in the early 1920s, and 1.73 for those born in the late 1920s.

The most dramatic shift occurred right at the turn of that decade, when the rate fell to 0.23. Mathematical modeling pegged the best estimate for the change point to July 1929. While the model suggests an abrupt change in dementia rates, Derby noted that this might partly be the result of small sample size; the post-1929 cohorts totaled only 350 people, with just three cases of dementia among them. “If there were more people in the analysis, the trend might be smoother,” Derby wrote to Alzforum. Nonetheless, the findings were statistically significant, and Derby believes the data are picking up a real decline in dementia risk at around this time point.

The researchers adjusted the model for the potential confounding factors of age, sex, and education level, as well as race. Later birth cohorts were more ethnically diverse than earlier ones, but the changing demographics of the population did not explain the drop in dementia cases, since researchers saw the same decline among white participants as well.

What might explain it? The researchers found marked decreases in the rates of heart attack and stroke in later birth cohorts, but after adjusting the model to account for this, the drop in dementia incidence in those born after 1929 remained unchanged. However, cardiovascular health was assessed only by participants’ self-reported medical history, and thus the analysis might have missed more subtle signs of vascular disease, the authors noted. In particular, the researchers had no data on factors such as how well controlled a person’s hypertension or diabetes was. They suggested that cardiovascular health might still be a factor, but not the only one. Other possibilities, such as better nutrition, were not assessed in this study. A healthy diet has been shown to lower the risk of Alzheimer’s disease.

“Changes in diet, especially for the mother during pregnancy, may be a crucial factor,” agreed Walter Rocca at the Mayo Clinic in Rochester, Minnesota. In addition, Rocca pointed out that people born in 1929 or after would have been teenagers or younger at the end of World War II, and thus their developing brains may have particularly reaped the benefits of the societal and medical changes that occurred at that time (see full comment below).

While previous epidemiological studies did not specifically examine birth years, those older findings are roughly congruent with the Einstein Aging Study data, reporting the greatest drop in dementia cases after 1990, the authors noted. People born after 1929 would have entered their 60s in that decade. Most cases of late-onset dementia occur after age 60. The Rotterdam Study found a 25 percent decrease in dementia incidence in the 1990s, while the Framingham Heart Study recently reported that incidence dropped starting in the late 1980s and continued to decline into the 2010s (Schrijvers et al., 2012; Satizabal et al., 2016).

Meanwhile, although these lower rates of dementia are good news, researchers agree the case numbers will still soar as populations worldwide continue to get older (Oct 2016 news; Kosteniuk et al., 2016). The numbers of new cases also continue to climb in much of the developing world (May 2012 news; Jun 2013 news). In addition, rising rates of diabetes, a risk factor for Alzheimer’s, are expected to reverse some of the positive health trends.—Madolyn Bowman Rogers