VItamin K Inhibition and NeurocoGnition (VIKING)

Use of Vitamin K Antagonist and Neurocognitive Disorders in Older Adults : a Retrospective Study With Exposed and Non-exposed Groups

The primary objective of this study is to determine whether patients usually taking Vitamin K Antagonists (VKAs) exhibit a poorer global cognitive performance than control patients (matched on age, gender and indication for anticoagulation) taking direct oral anticoagulants (DOACs).

The secondary objectives are:

• to determine whether patients usually taking VKAs are more likely to have moderate to severe cognitive disorders than matched controls taking DOACs.
• to determine whether VKAs intake is associated with poorer executive functions.
• to determine on CT scans whether the VKAs intake is associated with a greater volume of vascular calcifications in the brain compared to the use of DOACs.

VKAs are the most common drugs in the treatment and prophylaxis of thromboembolic events in older adults. Their action is mediated by decrease in the bioavailability of the active form of vitamin K. However, vitamin K participates in brain health and function by regulating the synthesis of sphingolipids, a constituent of the myelin sheath and the neurons membrane, and through the biological activation of vitamin K-dependent proteins (VKDPs) involved in neuron survival. Epidemiological studies have reported a positive association between higher serum vitamin K concentration and better verbal episodic memory performance in older adults, and an inverse association between dietary vitamin K intakes and cognitive complaint/cognitive disorders/behavioral disorders. VKAs, which deplete the active form of vitamin K, may thus be responsible for neurological disorders. CNS abnormalities were observed in newborns exposed in utero to VKA. Similarly, in two cross-sectional studies, the use of VKAs was directly associated with cognitive disorders in older adults, and with a lower volume of gray matter in the hippocampus.

However, the main limitation of these previous studies was that the different associations reported may actually be explained by the thromboembolic pathology justifying the use of VKA such as atrial fibrillation with potential adverse consequences on the brain.

Thus, the use of DOACs could serve as an ideal comparator, as their indications are similar to those of VKAs but which mechanism does not interfere with vitamin K.

The investigators hypothesize that 1) geriatric patients usually taking VKAs may have lower cognitive performance than those usually taking DOACs; 2) there is an association between VKA intake and cognitive performance in geriatric patients, including after adjustment on the indication for anticoagulation; and 3) that geriatric patients usually taking VKAs exhibit brain changes compared to those usually taking DOACs, including greater calcification burden.

Inclusion Criteria:

• Age 70 years and over

• To be seen in consultation or day hospital in the department of geriatrics from 01/01/2015 to 31/12/2016

• Exposed :

  • Patients who have been taking VKA for at least 3 months for atrial fibrillation or pulmonary embolism, with INR between 2 and 3

• Non-exposed:

  • Patients who have been taking DOAC for at least 3 months for atrial fibrillation or pulmonary embolism
  • Matched on age (± 5 years), gender and indication for anticoagulation

Exclusion Criteria:

• Severe kidney failure (creatinine clearance < 30 mL/min)
• Language other than French