Plasma β-Amyloid and Cognitive Decline

Objectives: To determine if plasma beta-amyloid (A beta) levels (1) can be linked to specific cognitive changes that constitute conversion to Alzheimer disease (AD) and (2) correspond to cognitive change independent of dementia. Design: Longitudinal study including 3 visits during approximately 41/2 years (2000-2006). Setting: Northern Manhattan community. Participants: Eight hundred eighty individuals from a population-based and ethnically diverse sample who had 2 plasma A beta measurements and were dementia free at the time of the first A beta sample; 481 remained cognitively healthy, 329 were cognitively or functionally impaired but not demented at any point, and 70 developed AD. Main Outcome Measures: General estimating equations tested the association between plasma A beta (baseline and change in values) and cognitive change (composite score and memory, language, and visuospatial indices). Results: High baseline plasma A beta 42 (P=.01) and A beta 40 (P=.01) and decreasing/relatively stable A beta 42 (P=.01) values were associated with faster decline in multiple cognitive domains. In those who remained cognitively healthy, high baseline plasma A beta 42 (P=.01) and decreasing/relatively stable plasma A beta 42 (P=.01) was associated with faster cognitive decline, primarily in memory. Conclusions: The association between plasma A beta and multiple aspects of cognition more clearly specifies the previously documented downward trajectory of plasma A beta with AD onset. The predominant association with memory seen only in healthy elderly individuals also suggests that plasma A beta is linked with even earlier neurologic changes that may or may not culminate in dementia.