Different Risks for Amyloid, Neurodegeneration

by Kristin Jenkins for MedPage Today:Different factors appear to protect against amyloid deposition and neurodegeneration, the two hallmarks of Alzheimer's disease, according to an analysis from the Mayo Clinic Study of Aging.Aside from the known risk factors of older age, female gender, and APOE status, only midlife dyslipidemia was associated with amyloid deposition -- while midlife obesity, smoking, diabetes, hypertension, and cardiac and metabolic conditions were tied to neurodegeneration, according to Prashanthi Vemuri, PhD, of the Mayo Clinic in Rochester, Minn., and colleagues.Intellectual enrichment, however, wasn't a significant predictor of amyloid deposition or neurodegeneration, they reported online in JAMA Neurology.These data "provide more insight into the complex picture of cognitive aging," Ronald Petersen, MD, PhD, of the Mayo Clinic and a co-author on the paper, told MedPage Today.Petersen added that the fact that the differences in amyloid deposition and neurodegeneration and how they influence development of Alzheimer's disease "is a hot topic of investigation. The more we learn about the biomarkers, the more we learn about risk and protective factors. The notion of exceptional brain aging is relevant here -- why some people have a lower degree of Alzheimer's disease-causing brain changes even at advanced ages and higher genetic risk of Alzheimer's disease."For the current study, the researchers analyzed prospective data from 942 individuals ages 70 to 90 from Olmsted County who were enrolled in the Mayo Clinic Study of Aging and had both magnetic resonance imaging (MRI) and Pittsburgh compound B-positron emission tomography (PET) scans. The average age was 80 and 45% of the cohort was female.Vemuri and colleagues looked at several factors that could potentially be tied to Alzheimer's pathology, including age, sex, APOE status, intellectual enrichment, and midlife risk factors -- physical inactivity, obesity, smoking, diabetes, hypertension, and dyslipidemia -- as well as the total number of late-life cardiac and metabolic conditions.The association between midlife dyslipidemia and amyloid deposition is consistent with other research, the authors said, suggesting that cholesterol plays an important role in Alzheimer's pathogenesis via amyloid but not neurodegeneration.Given that other midlife risk factors weren't associated with amyloid deposition, it could be that these are "catalysts for the neuronal processes but not amyloid deposition," they wrote.Although many midlife risk factors were associated with neurodegeneration, intellectual enrichment was not: "Our work previously showed that the effect of intellectual enrichment on AD biomarkers may be minimal, but that it has a larger effect on delaying the onset of cognitive impairment, suggesting that it is mainly protective against cognitive decline," the researchers wrote.Individuals age 85 and up who didn't have significant evidence of Alzheimer's pathology (either amyloid or neurodegeneration) were considered "exceptional agers." In this subgroup analysis, there were small-to-moderate effect sizes (Cohen's d >0.2) of several variables except job score and midlife hypertension in predicting exceptional aging without any Alzheimer's disease pathology.This suggests that protection against both amyloid deposition and neurodegeneration is important, the researchers wrote."'Exceptional aging' without ADP may be possible with a greater number of protective factors across the lifespan, but this warrants further investigation," they wrote, adding that study of the independent and combined protective factors for amyloid and neurodegeneration "will enable better prevention strategies to delay the onset and progression of Alzheimer['s] disease."The study was limited by the fact that it focused on a limited number of protective factors, the groups were not age-matched, and neurodegeneration was a surrogate for tau pathology; future studies should use tau PET imaging, they urged.Still, Vemuri said the findings reinforce the idea that "advanced age and greater genetic risk of Alzheimer's does not imply that individuals will go on to develop Alzheimer's disease. Therefore, management of overall health of an individual is important for healthier brain aging."Source: http://bit.ly/2pmQz30