Does CRP Protect Families from Dementia?

by Michael Smith for MedPage Today:Healthy aging -- and cognitive health in particular -- may run in families and may be linked to high levels of an important marker for cardiovascular disease, researchers reported.In a cohort of men 75 and older without dementia, high levels C-reactive protein (CRP) were associated with a low likelihood that relatives would have dementia, according to Jeremy Silverman, PhD, of Mount Sinai School of Medicine in New York City, and colleagues.In a separate cohort -- men and women 85 and older -- the same relationship held true but was even stronger, Silverman and colleagues reported online in Neurology.The finding implies that high levels of C-reactive protein in such older people "may constitute a phenotype for familial -- and thus possibly genetic -- successful cognitive aging," the researchers argued."In very elderly people with good cognition, higher levels of C-reactive protein, which is related to inflammation, are associated with better memory," Silverman said in a statement. In the current study, the researchers found "that the higher the level of this protein in the study participant, the lower the risk for dementia in their parents and siblings."The finding is to some degree counter-intuitive, he and his colleagues noted, since CRP is a marker for systemic inflammation and in younger people is associated with an increased risk of cardiovascular disease.In addition, the protein is associated with worse cognition in "younger" elderly people, he said. "Thus, for very old people who remain cognitively healthy, those with a high protein level may be more resistant to dementia," he added.One implication may be that there is a "resilient" genetic make-up that allows people to age without dementia, despite the presence of such risk factors as C-reactive protein, commented Aron Buchman, MD, and David Bennett, MD, both of Rush University Medical Center in Chicago."The idea of resilience is conceptually attractive," they argued in an accompanying editorial in the journal, and there is increasing interest in finding patterns of healthy aging that could in turn lead to the identification of the genes involved.One of the important aspects of the study by Silverman and colleagues, they argued, is that it switches the focus from "disease and deterioration to ... resilience and healthy cognitive aging."Other outside experts said the finding is interesting but preliminary."It may show us who can resist dementia and this could lead to treatments," according to Constantine Lyketsos, MD, of Johns Hopkins University in Baltimore.But, in an email to MedPage Today and ABC News, Lyketsos added: "It needs to be replicated. I would not make too big a deal of it at this stage."And Richard Caselli, MD, of the Mayo Clinic in Scottsdale, Ariz., cautioned: "As is always the case in science, this observation should be replicated before being accepted as fact."But, he added, if it were confirmed, that would imply that people with high C-reactive protein have some protection against dementia."It seems unlikely that high CRP itself is good for longevity and remaining dementia-free," Caselli said in an email to MedPage Today and ABC News, "but rather some other undiscovered factor protecting these unusual high CRP older folks."Silverman and colleagues first studied a convenience sample of 277 cognitively intact male veterans at least 75 years old and 1,329 of their parents and siblings, who were assessed for dementia by interviewing the vets.They followed the same procedure in a replication sample of 202 relatives of 51 cognitively intact men and women in the community at large who were at least 85.Both cohorts were divided into thirds based on levels of C- reactive protein, and their relatives' risk for dementia was assessed as a function of the proband's log-transformed C-reactive protein level.In the first cohort, Silverman and colleagues found, the veterans reported a total of 40 relatives from 37 families with dementia. In a proportional hazards analysis, that yielded a hazard ratio for dementia of 0.55 (95% CI 0.41 to 0.74, P<0.02).In the replication sample, the men and women reported a total of nine cases of dementia among their 202 relatives, yielding a hazard ratio for dementia of 0.15 (95% CI 0.06 to 0.37, P<0.0001).One possible explanation of the findings might be an increased rate of mortality among relatives of those with the highest levels of CRP, but an analysis showed that the link between the protein and mortality in relatives was not significant.The researchers cautioned that the number of cases of dementia was small and logistical difficulties and expense precluded direct assessment of relatives.Nonetheless, they concluded, "relatively high levels of (CRP) may be a useful biological phenotype for familial successful cognitive aging (that) may help identify relevant genes, leading to development of interventions for maintaining cognitive function."Source: http://www.medpagetoday.com/Neurology/Dementia/34216