Plasma β-Amyloid Linked to Cognitive Decline

Abstract

JAMA Association of Plasma β-Amyloid Level and Cognitive Reserve With Subsequent Cognitive Decline Kristine Yaffe, MD; Andrea Weston, MPH; Neill R. Graff-Radford, MBBCh; Suzanne Satterfield, MD, DrPh; Eleanor M. Simonsick, PhD; Steven G. Younkin, MD, PhD; Linda H. Younkin, PhD; Lewis Kuller, MD, DrPh; Hilsa N. Ayonayon, PhD; Jingzhong Ding, MD, PhD; Tamara B. Harris, MD, MS Context: Lower plasma β-amyloid 42 and 42/40 levels have been associated with incident dementia, but results are conflicting and few have investigated cognitive decline among elders without dementia. Objective: To determine if plasma β-amyloid is associated with cognitive decline and if this association is modified by measures of cognitive reserve. Design, Setting, and Participants: We studied 997 black and white community-dwelling older adults from Memphis, Tennessee, and Pittsburgh, Pennsylvania, who were enrolled in the Health ABC Study, a prospective observational study begun in 1997-1998 with 10-year follow-up in 2006-2007. Participant mean age was 74.0 (SD, 3.0) years; 55.2% (n = 550) were female; and 54.0% (n = 538) were black. Main Outcome Measures: Association of near-baseline plasma β-amyloid levels (42 and 42/40 measured in 2010) and repeatedly measured Modified Mini-Mental State Examination (3MS) results. Results: Low β-amyloid 42/40 level was associated with greater 9-year 3MS cognitive decline (lowest β-amyloid tertile: mean change in 3MS score, −6.59 [95% confidence interval [CI], −5.21 to −7.67] points; middle tertile: −6.16 [95% CI, −4.92 to −7.32] points; and highest tertile: −3.60 [95% CI, −2.27 to −4.73] points; P APOE ] e4 status and after excluding the 72 participants with incident dementia. Measures of cognitive reserve modified this association whereby among those with high reserve (at least a high school diploma, higher than sixth-grade literacy, or no APOE e4 allele), β-amyloid 42/40 was less associated with multivariate adjusted 9-year decline. For example, among participants with less than a high school diploma, the 3MS score decline was −8.94 (95% CI, −6.94 to −10.94) for the lowest tertile compared with −4.45 (95% CI, −2.31 to −6.59) for the highest tertile, but for those with at least a high school diploma, 3MS score decline was −4.60 (95% CI, −3.07 to −6.13) for the lowest tertile and −2.88 (95% CI, −1.41 to −4.35) for the highest tertile ( P = .004 for interaction). Interactions were also observed for literacy ( P = .005) and for APOE e4 allele ( P = .02). Conclusion: Lower plasma β-amyloid 42/40 is associated with greater cognitive decline among elderly persons without dementia over 9 years, and this association is stronger among those with low measures of cognitive reserve. JAMA. 2011;305(3):261-266.