Missing Data Analyses
880 of 2412 non-demented participants seen in 1999 had Aβ samples from baseline and second follow-up. See for demographic characteristics and mean Aβ values. Overall, these subjects were younger (76.04 versus 77.99; p < .01) and had higher composite cognitive scores (0.32 versus 0.19; p < .01) than subjects without complete Aβ data but education, sex, ethnic group, and APOEε4 status were comparable. Of the 880 with available Aβ samples, individuals with incident AD were significantly older (F = 67.20, p < .01) and had fewer years of formal education (F = 102.34, p < .01) than the healthy elders in the sample.
Baseline and Change Characteristics for Cognition and Aβ
Plasma Aβ and Cognition at Baseline
After adjusting for age, sex, and ethnic group, multivariate general linear models in the entire sample revealed no difference in any of the baseline cognitive scores(composite, memory, language, or visuospatial) by baseline Aβ42(F = 1.24, p = .27) or Aβ40 (F = 1.08, p = .37)quartiles. Partial correlations adjusting for age revealed no association between composite cognitive score and continuous Aβ values at baseline [Aβ42 (r = −.02, p = .56); Aβ40 (r = .01, p = .78)].
GEE: Rate of Global Cognitive Change by Baseline Aβ
details the predictive value of baseline Aβ for cognitive change in the entire sample and healthy elders only. Aβ quartiles were comparable for both samples. In the entire sample, individuals in the top three Aβ42 quartiles declined faster than those in the lowest quartile. Results were largely comparable in the healthy elders. Individuals in the top three Aβ40 quartiles also declined faster than those in the lowest quartile. In the healthy elders, only the highest quartile declined faster than those in the lowest. The Aβ42:40 ratio was not a significant predictor. Beta values and significance levels were essentially identical when the data was examined by tertile, such that individuals in the highest two tertiles of both baseline Aβ40 and Aβ42 declined more quickly than those in the reference group. It should be noted that the significance was marginal in healthy elders who had the highest levels of Aβ42, and this was true when grouping by quartile or tertile.
GEE Models of Composite Cognitive Decline as a function of Aβ
GEE: Rate of Global Cognitive Change by Aβ Change
In the entire sample and healthy elders only, those with relatively stable or decreasing Aβ42 had faster cognitive decline than those with increasing Aβ42 (Entire Sample: β = −.02; p = .01; Healthy Elders: β = −.01; p = .02). Removing baseline Aβ42 values from these models did not change the results. Change in Aβ40 was not associated with cognitive change in either sample. In individuals with high risk Aβ42 profiles (highest baseline quartile and decreasing or relatively stable over time), incident AD cases had less education than those who remained dementia free over follow-up (age and ethnicity adjusted means 7.99 versus 11.74; F = 49.34, p < .01).
GEE: Cognitive Change in Specific Domains by Aβ
and outline the results regarding specific cognitive domains. In the entire sample, baseline Aβ42 predicted cognitive change in all three domains, with individuals in the highest Aβ42 quartile consistently declining faster than those in the lowest. Cognitive change in the second and third Aβ42 quartiles was less consistently different from that of the lowest quartile. Baseline Aβ40 quartile predicted: 1) change in memory with individuals in the second and third quartiles declining faster than those in the lowest; and 2) change in language with individuals in the highest quartile declining faster than those in the lowest. Finally, change in Aβ42 predicted change in memory and visuospatial scores, with relatively stable or decreasing Aβ42 predicting faster decline.
GEE Models of Specific Cognitive Decline in Entire Sample as a function of Aβ
GEE Models of Specific Cognitive Decline in Healthy Elders as a function of Aβ
In healthy elders, baseline Aβ42 quartile predicted change primarily in memory, with higher Aβ42 at baseline generally predicting faster decline. Baseline Aβ40 was generally unrelated to cognitive change although individuals in the 2nd quartile had faster memory decline than those in the lowest. Change in Aβ42 was not associated with change in any domain, although there was a trend toward faster memory decline in individuals with relatively stable or decreasing Aβ42, and the magnitude of the effect was identical to that in the entire sample. Finally, change in Aβ40 over time was not related to cognitive change in the entire sample or healthy elders.
We ran additional exploratory analyses examining the association between plasma Aβ and global cognition in: 1) the group of 329 individuals with cognitive or functional change but no dementia, and 2) the 70 cases of incident AD. Indeed, the beta coefficients were in the same direction and largely comparable in the 329 individuals as in the entire sample, and even stronger in the AD sample (e.g., −.04 to −.09). This was true for both baseline and change analyses. While the results were not statistically significant in these two additional groups, this likely reflected a lack of power in these smaller samples.