Activation of hemostasis and decline in cognitive function in older people.
OBJECTIVE
To determine whether activation of hemostatic function (thrombosis and fibrinolysis) is associated with cognitive decline in older people.


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.
Stott
David J
DJ
Academic Section of Geriatric Medicine, 3 Floor Queen Elizabeth Building, Royal Infirmary, Glasgow G31 2ER. d.j.stott@clinmed.gla.ac.uk
Robertson
Michele
M
Rumley
Ann
A
Welsh
Paul
P
Sattar
Naveed
N
Packard
Christopher J
CJ
Shepherd
James
J
Trompet
Stella
S
Westendorp
Rudi G J
RG
de Craen
Anton J M
AJ
Jukema
J Wouter
JW
Buckley
Brendan
B
Ford
Ian
I
Lowe
Gordon D O
GD
D000203:Activities of Daily Living; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000097:blood* / Q000453:epidemiology; D015140:Dementia, Vascular / Q000097:blood* / Q000453:epidemiology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005500:Follow-Up Studies; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D008297:Male; D011516:Prothrombin / Q000378:metabolism; D012307:Risk Factors
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D011516:Prothrombin; D005340:Fibrinogen