Abstract:

OBJECTIVES: To determine if plasma β-amyloid (Aβ) 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 Aβ measurements and were dementia free at the time of the first Aβ 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 Aβ (baseline and change in values) and cognitive change (composite score and memory, language, and visuospatial indices). RESULTS: High baseline plasma Aβ42 (P = .01) and Aβ40 (P = .01) and decreasing/relatively stable Aβ42 (P = .01) values were associated with faster decline in multiple cognitive domains. In those who remained cognitively healthy, high baseline plasma Aβ42 (P = .01) and decreasing/relatively stable plasma Aβ42 (P = .01) was associated with faster cognitive decline, primarily in memory. CONCLUSIONS: The association between plasma Aβ and multiple aspects of cognition more clearly specifies the previously documented downward trajectory of plasma Aβ with AD onset. The predominant association with memory seen only in healthy elderly individuals also suggests that plasma Aβ is linked with even earlier neurologic changes that may or may not culminate in dementia.