Simple Interventions in Middle Age May Lower Alzheimer's Risk

Alzheimer's disease has a strong genetic component. For example, twin studies have implied that at least 60 percent of the risk of developing Alzheimer's is under genetic control. So what can middle-aged people with a parental history of Alzheimer's do to ward off the disease?

Bringing high blood pressure and inflammatory markers called cytokines to heel might be one way, a new study suggests.

The study was headed by Eric van Exel, M.D., Ph.D., a geriatric psychiatrist affiliated with the VU University Medical Center in Amsterdam, the Netherlands, and published in the November Archives of General Psychiatry.

The researchers conducted their study on some 400 middle-aged subjects (average age 50). Half had a parental history of Alzheimer's. Each of the subjects was evaluated for the APOE-e4 gene variant that has been strongly linked to Alzheimer's; for high blood pressure, which has also been strongly linked with Alzheimer's; and for inflammatory markers in the blood called cytokines. Cytokines have been found in abundance in and around amyloid plaques in the brain, implying that they participate in the Alzheimer's neurodegenerative process. The researchers then compared the APOE-e4, blood pressure, and cytokine results for the two study groups.

The APOE-e4 gene variant was present significantly more often in subjects with a parental history of Alzheimer's than in the control group—that is, in 47 percent of the former and in 21 percent of the latter. So was high blood pressure; it was present in 40 percent of subjects with a parental history of Alzheimer's, but in only 29 percent of subjects without. And significantly higher levels of inflammatory cytokines were found in the blood of the group with a parental history of Alzheimer's than in the control group. Furthermore, these results remained firm even when some possibly confounding factors such as education, stress, smoking, fat intake, and physical activity were considered.

Thus, the researchers concluded that in addition to the APOE-e4 gene variant, high blood pressure and inflammatory cytokines “in middle age are early risk factors for Alzheimer's in old age.”

This news may disturb middle-aged individuals with a parental history of Alzheimer's. But it could also have a silver lining—helping them avoid Alzheimer's themselves.

For instance, if these individuals find that they have high blood pressure and then bring it under control, it might help keep them from developing Alzheimer's, van Exel suggested to Psychiatric News. “We feel that it is important that both doctors/psychiatrists and middle-aged first-degree relatives of subjects diagnosed with Alzheimer's should realize that prevention of high blood pressure is the first step to reduce the incidence of Alzheimer's.”

Support for this position comes not just from the results that he and his group obtained but also from findings reported by French researchers in the October 24, 1998, Lancet, van Exel pointed out. The study included more than 2,000 individuals aged 60 or older with high blood pressure and no dementia. Over a two-year period, half the subjects got treatment for their high blood pressure, whereas the other half got a placebo. At the end of that time, the two groups were compared regarding the development of dementia. The group that had received medication for high blood pressure had a 50 percent lower incidence of dementia than the control group.

If middle-aged persons with a parental history of Alzheimer's took a nonsteroidal anti-inflammatory drug (NSAID) to counter inflammatory cytokines in their bodies, that too might possibly help prevent or delay the development of Alzheimer's, van Exel said, although the evidence in that domain is somewhat conflicting. For example, a study reported in the May 6, 2008, Neurology suggested that the NSAID ibuprofen could protect against Alzheimer's. But a study reported in the July 2008 Archives of Neurology implied that two other NSAIDs—naproxen and celecoxib—did not possess this capability (Psychiatric News, July 4, 2008).

Provided they get the funding, van Exel and his team will be following their cohort to see whether lowering high blood pressure or inflammatory cytokines can prevent Alzheimer's.

The study was funded by the European Union, the International Foundation for Alzheimer Research in the Netherlands, and the U.S. National Institute on Aging.

An abstract of “Vascular Factors and Markers of Inflammation in Offspring With a Parental History of Late-Onset Alzheimer Disease” is posted at <http://archpsyc.ama-assn.org/cgi/content/abstract/66/11/1263>.