OBJECTIVE: To determine whether activation of hemostatic function (thrombosis and fibrinolysis) is associated with cognitive decline in older people. METHODS AND RESULTS: We studied 5804 people (age, 70-82 years) in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Mean follow-up was 3.2 years, including annual measurement of speed of information processing (letter, digit coding, and Stroop), verbal memory (picture-word naming), and basic and instrumental activities of daily living. Raised levels of markers of thrombin generation (d-dimer and prothrombin fragment 1+2) were associated independently with increased rate of cognitive decline (eg, Stroop increased by 4.44 s [SEM, 0.68] in bottom tertile of d-dimer compared to 5.46 [SEM, 0.71] in highest tertile; P<0.05) and deterioration in activities of daily living. This increased rate of decline was attenuated but not removed when subjects with incident nonfatal stroke were omitted from the analysis. It also persisted when adjustments were made for inflammation (C-reactive protein and IL-6). CONCLUSIONS: Older patients with increased markers of thrombin generation (d-dimer and prothrombin fragment 1+2) are at increased risk for cognitive decline and deterioration in ability to perform activities of daily living. This is likely attributable to increased risk of cerebral ischemic damage (including covert disease) associated with prothrombotic states.
OBJECTIVE: To determine whether activation of hemostatic function (thrombosis and fibrinolysis) is associated with cognitive decline in older people. METHODS AND RESULTS: We studied 5804 people (age, 70-82 years) in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Mean follow-up was 3.2 years, including annual measurement of speed of information processing (letter, digit coding, and Stroop), verbal memory (picture-word naming), and basic and instrumental activities of daily living. Raised levels of markers of thrombin generation (d-dimer and prothrombin fragment 1+2) were associated independently with increased rate of cognitive decline (eg, Stroop increased by 4.44 s [SEM, 0.68] in bottom tertile of d-dimer compared to 5.46 [SEM, 0.71] in highest tertile; P<0.05) and deterioration in activities of daily living. This increased rate of decline was attenuated but not removed when subjects with incident nonfatal stroke were omitted from the analysis. It also persisted when adjustments were made for inflammation (C-reactive protein and IL-6). CONCLUSIONS: Older patients with increased markers of thrombin generation (d-dimer and prothrombin fragment 1+2) are at increased risk for cognitive decline and deterioration in ability to perform activities of daily living. This is likely attributable to increased risk of cerebral ischemic damage (including covert disease) associated with prothrombotic states.
Authors: S R Gillett; L A McClure; P W Callas; E L Thacker; F W Unverzagt; V G Wadley; A J Letter; M Cushman Journal: J Thromb Haemost Date: 2018-06-06 Impact factor: 5.824
Authors: Mitchel A Kling; John Q Trojanowski; David A Wolk; Virginia M Y Lee; Steven E Arnold Journal: Alzheimers Dement Date: 2012-11-22 Impact factor: 21.566
Authors: Terence J Quinn; Jahad Alghamdi; Sandosh Padmanabhan; David J Porteous; Blair H Smith; Lynne Hocking; Ian J Deary; John Gallacher; Martina Messow; David J Stott Journal: Age (Dordr) Date: 2015-08-01
Authors: Cláudia N Ferreira; Maria G Carvalho; Karina B Gomes; Helton J Reis; Ana-Paula Fernandes; András Palotás; Marinez O Sousa Journal: Exp Biol Med (Maywood) Date: 2014-07-29
Authors: Senthil K Vasan; Klaus Rostgaard; Henrik Ullum; Mads Melbye; Henrik Hjalgrim; Gustaf Edgren Journal: PLoS One Date: 2015-06-04 Impact factor: 3.240
Authors: Nicholas L Smith; Jennifer E Huffman; David P Strachan; Jie Huang; Abbas Dehghan; Stella Trompet; Lorna M Lopez; So-Youn Shin; Jens Baumert; Veronique Vitart; Joshua C Bis; Sarah H Wild; Ann Rumley; Qiong Yang; Andre G Uitterlinden; David J Stott; Gail Davies; Angela M Carter; Barbara Thorand; Ozren Polašek; Barbara McKnight; Harry Campbell; Alicja R Rudnicka; Ming-Huei Chen; Brendan M Buckley; Sarah E Harris; Annette Peters; Drazen Pulanic; Thomas Lumley; Anton J M de Craen; David C Liewald; Christian Gieger; Susan Campbell; Ian Ford; Alan J Gow; Michelle Luciano; David J Porteous; Xiuqing Guo; Naveed Sattar; Albert Tenesa; Mary Cushman; P Eline Slagboom; Peter M Visscher; Tim D Spector; Thomas Illig; Igor Rudan; Edwin G Bovill; Alan F Wright; Wendy L McArdle; Geoffrey Tofler; Albert Hofman; Rudi G J Westendorp; John M Starr; Peter J Grant; Mahir Karakas; Nicholas D Hastie; Bruce M Psaty; James F Wilson; Gordon D O Lowe; Christopher J O'Donnell; Jacqueline C M Witteman; J Wouter Jukema; Ian J Deary; Nicole Soranzo; Wolfgang Koenig; Caroline Hayward Journal: Circulation Date: 2011-04-18 Impact factor: 29.690