Direct Relationship Seen Between Plasma Aβ Levels and Cognitive Decline (part 2)

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Pam Harrison (Medscape Today)

Aging Project

The amyloid cascade hypothesis suggests that Alzheimer's disease develops subsequent to aberrant metabolism of glycoproteins, the precursors to amyloid, the authors write. Aβ40 and Aβ42 then accumulate, and this accumulation is considered the primary trigger for the development of Alzheimer's disease. Previous research indicates that plasma Aβ levels decrease as brain levels increase, suggesting that plasma Aβ level may be used as a biomarker of disease risk.

In this study, participants were drawn from the Washington Heights and Inwood Columbia Aging Project and represented 3 broadly defined ethnic groups: Caribbean Hispanic, black, and white. All participants were free of dementia at the time of the first Aβ sample; at follow-up, 481 patients remained cognitively healthy, 329 were cognitively or functionally impaired but not demented at any point, and 70 developed Alzheimer's disease.

Investigators then determined whether Aβ levels could be linked to either specific cognitive changes that constitute conversion to Alzheimer's disease or whether they corresponded to cognitive change independent of dementia. Cognitive change consisted of a composite score and memory, language, and visuospatial indices.

When researchers examined cognitive change in specific domains by Aβ, they determined that baseline Aβ42 predicted cognitive change in all 3 domains in the overall sample, with those in the highest Aβ quartile "consistently declining faster" than those in the lowest. "Baseline Aβ40 quartile predicted change in memory," the authors add, with those in the second and third quartiles declining faster than those in the lowest quartile.

Baseline Aβ40 quartiles also predicted 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," the researchers add. Among the group who remained cognitively healthy during the study interval, baseline Aβ42 predicted change primarily in memory, with higher baseline levels generally predicting faster decline.

In contrast, baseline Aβ40 was generally unrelated to cognitive change in the same healthy elderly group, and change in Aβ42 was not associated with change in any domain. Finally, change in Aβ40 over time was not related to cognitive change in either the overall sample or the cognitively healthy.

Relatively Rapid Decline

As the authors point out, the relatively rapid cognitive decline seen as