Alzheimer's Protein Rises With Age, Tied to Cognition Deficits

by Michael Smith for MedPage TodayEven in cognitively healthy adults, too much of the protein linked to Alzheimer's disease appears to affect some aspects of cognition, researchers reported.In a cross-sectional analysis of adults ages 30 through 89, the protein beta-amyloid increased with age, and higher levels were associated with deterioration of some cognitive functions, according to Kristen Rodrigue, PhD, of the University of Texas Dallas, and colleagues.And about one in five of those over 60 had markedly elevated deposition of the protein based on PET imaging for beta-amyloid, with a corresponding decline in some functions, Rodrigue and colleagues reported online and in the Feb. 7 issue of Neurology.The researchers noted that beta-amyloid deposition in the brain is a hallmark of Alzheimer's and plays a key role in most theories about the origins of the disease.Beta-amyloid deposition begins before the clinical signs of Alzheimer's are apparent, they noted, but the effect of those early deposits on cognition are not well understood.To help clarify the issue, Rodrigue and colleagues enrolled volunteers who were taking part in a larger study, the Dallas Lifespan Brain Study, and asked them to have a PET scan for beta-amyloid and also take several tests of cognitive function.The researchers also tested for the apolipoprotein E4 gene, which is associated with an increased risk of Alzheimer's disease.The 137 participants who volunteered were well-educated (with an average of more than 16 years of schooling) and cognitively healthy (with an average score on the Mini-Mental State Examination of 29.3).The cognitive function tests – taken twice by each participant -- covered five domains: processing speed, working memory, episodic memory, crystallized abilities, and fluid reasoning.The researchers found that beta-amyloid levels increased in a linear fashion with age, but not with sex or the combination of age and sex. The age association was significant at P<0.001.The sample population included a subset – 18 people older than 60 -- whose beta-amyloid levels were higher than the upper limit of the 95% confidence interval for the age analysis.But even with those people removed, the researchers still found a significant effect (at P<0.001) of age. However, the effect became non-significant (at P=0.08) when those 60 and under were excluded.Analysis of cognitive function showed a dose-response effect – with higher levels linked to worse performance – on processing speed and fluid reasoning that was significant at P=0.04 and P<0.05, respectively.There was no effect on working memory, episodic memory, or crystallized abilities, Rodrigue and colleagues found.In the subgroup with elevated beta-amyloid, the researchers found a significant affect on three domains -- processing speed, working memory, and fluid reasoning.But in the full sample – excluding the elevated subgroup – the only domain affected was fluid reasoning, they reported.Interestingly, among the 18 people with elevated beta-amyloid, 38% had the ApoE4 gene, compared with 15% of the remaining volunteers.The researchers cautioned that the study group might not reflect the population as a whole. In particular, many 70-to-89-year-olds in the general population might not meet the cognitive and physical criteria for the study, and might be more likely to have elevated beta-amyloid.Source: http://www.medpagetoday.com/Neurology/AlzheimersDisease/30978