Olivia I Okereke1, Weiming Xia, Dennis J Selkoe, Francine Grodstein. 1. Division of Aging and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Third Floor, Boston, MA 02115, USA. olivia.okereke@channing.harvard.edu
Abstract
BACKGROUND: Plasma levels of amyloid beta peptide (Abeta) are potential biomarkers of early cognitive impairment and decline and of Alzheimer disease risk. OBJECTIVE: To relate midlife plasma Abeta measures and 10-year change in plasma Abeta measures since midlife to late-life cognitive decline. DESIGN: Prospective study of a population-based sample. SETTING: Academic research. PARTICIPANTS: Plasma Abeta40 and Abeta42 levels were measured in 481 Nurses' Health Study participants in late midlife (mean age, 63.6 years) and again 10 years later (mean age, 74.6 years). Cognitive testing also began 10 years after the initial blood draw. Participants completed 3 repeated telephone-based assessments (mean span, 4.1 years). Multivariable linear mixed-effects models were used to estimate relations of midlife plasma Abeta40 to Abeta42 ratios and Abeta42 levels to late-life cognitive decline, as well as relations of 10-year change in Abeta40 to Abeta42 ratios and Abeta42 levels to cognitive decline. MAIN OUTCOME MEASURES: The 3 primary outcomes were the Telephone Interview for Cognitive Status (TICS) findings, a global score averaging the results of all tests (TICS, immediate and delayed verbal recall, category fluency, and attention), and a verbal memory score averaging the results of 4 tests of verbal recall. RESULTS: Higher midlife plasma Abeta40 to Abeta42 ratios were associated with worse late-life decline on the global score (P = .04 for trend). Furthermore, increase in Abeta40 to Abeta42 ratios since midlife predicted greater decline in the global score (P = .03 for trend) and in the TICS (P = .02 for trend). There was no association of cognitive decline with midlife plasma Abeta42 levels alone or with change in Abeta42 levels since midlife. CONCLUSION: In this large community-dwelling sample, higher plasma Abeta40 to Abeta42 ratios in late midlife and increases in Abeta40 to Abeta42 ratios 10 years later were significantly associated with greater decline in global cognition at late life.
BACKGROUND: Plasma levels of amyloid beta peptide (Abeta) are potential biomarkers of early cognitive impairment and decline and of Alzheimer disease risk. OBJECTIVE: To relate midlife plasma Abeta measures and 10-year change in plasma Abeta measures since midlife to late-life cognitive decline. DESIGN: Prospective study of a population-based sample. SETTING: Academic research. PARTICIPANTS: Plasma Abeta40 and Abeta42 levels were measured in 481 Nurses' Health Study participants in late midlife (mean age, 63.6 years) and again 10 years later (mean age, 74.6 years). Cognitive testing also began 10 years after the initial blood draw. Participants completed 3 repeated telephone-based assessments (mean span, 4.1 years). Multivariable linear mixed-effects models were used to estimate relations of midlife plasma Abeta40 to Abeta42 ratios and Abeta42 levels to late-life cognitive decline, as well as relations of 10-year change in Abeta40 to Abeta42 ratios and Abeta42 levels to cognitive decline. MAIN OUTCOME MEASURES: The 3 primary outcomes were the Telephone Interview for Cognitive Status (TICS) findings, a global score averaging the results of all tests (TICS, immediate and delayed verbal recall, category fluency, and attention), and a verbal memory score averaging the results of 4 tests of verbal recall. RESULTS: Higher midlife plasma Abeta40 to Abeta42 ratios were associated with worse late-life decline on the global score (P = .04 for trend). Furthermore, increase in Abeta40 to Abeta42 ratios since midlife predicted greater decline in the global score (P = .03 for trend) and in the TICS (P = .02 for trend). There was no association of cognitive decline with midlife plasma Abeta42 levels alone or with change in Abeta42 levels since midlife. CONCLUSION: In this large community-dwelling sample, higher plasma Abeta40 to Abeta42 ratios in late midlife and increases in Abeta40 to Abeta42 ratios 10 years later were significantly associated with greater decline in global cognition at late life.
Authors: Sarah E Vermeer; Niels D Prins; Tom den Heijer; Albert Hofman; Peter J Koudstaal; Monique M B Breteler Journal: N Engl J Med Date: 2003-03-27 Impact factor: 91.245
Authors: Robert S Wilson; Julie A Schneider; Lisa L Barnes; Laurel A Beckett; Neelum T Aggarwal; Elizabeth J Cochran; Elizabeth Berry-Kravis; Julie Bach; Jacob H Fox; Denis A Evans; David A Bennett Journal: Arch Neurol Date: 2002-07
Authors: Jian-Ming Li; Zhi-Qin Xue; Si-Hao Deng; Xue-Gang Luo; Peter R Patrylo; Gregory W Rose; Huaibin Cai; Yan Cai; Xiao-Xin Yan Journal: Neurotox Res Date: 2012-10-05 Impact factor: 3.911
Authors: Fei Song; Anne Poljak; Michael Valenzuela; Richard Mayeux; George A Smythe; Perminder S Sachdev Journal: J Alzheimers Dis Date: 2011 Impact factor: 4.472
Authors: Laura D Baker; Sanjay Asthana; Brenna A Cholerton; Charles W Wilkinson; Stephen R Plymate; Pattie S Green; George R Merriam; Mark A Fishel; G Stennis Watson; Monique M Cherrier; Monica L Kletke; Pankaj D Mehta; Suzanne Craft Journal: Neurobiol Aging Date: 2011-08-19 Impact factor: 4.673
Authors: Michael C Donohue; Setareh H Moghadam; Allyson D Roe; Chung-Kai Sun; Steven D Edland; Ronald G Thomas; Ronald C Petersen; Mary Sano; Douglas Galasko; Paul S Aisen; Robert A Rissman Journal: Alzheimers Dement Date: 2014-10-07 Impact factor: 21.566