Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia behind Alzheimer's disease (AD).It is estimated that 40% of AD patients also have some form of VCID. One promising therapeutic for AD is anti-A␤ immunotherapy, which uses antibodies against A␤ to clear it from the brain. While successful in clearing A␤ and improving cognition in mice, anti-A␤ immunotherapy failed to reach primary cognitive outcomes in several different clinical trials. We hypothesized that one potential reason the anti-A␤ immunotherapy clinical trials were unsuccessful was due to this high percentage of VCID comorbidity in the AD population. We used our unique model of VCID-amyloid comorbidity to test this hypothesis. We placed 9-month-old wild-type and APP/PS1 mice on either a control diet or a diet that induces hyperhomocysteinemia (HHcy). After being placed on the diet for 3 months, the mice then received intraperotineal injections of either IgG2a control or 3D6 for another 3 months. While we found that treatment of our comorbidity model with 3D6 resulted in decreased total A␤ levels, there was no cognitive benefit of the anti-A␤ immunotherapy in our AD/VCID mice. Further, microhemorrhages were increased by 3D6 in the APP/PS1/control but further increased in an additive fashion when 3D6 was administered to the APP/PS1/HHcy mice. This suggests that the use of anti-A␤ immunotherapy in patients with both AD and VCID would be ineffective on cognitive outcomes.

Since the rate of adverse gastrointestinal events was lower (23% versus 38%, p = 0.02) in the group receiving the lower dose, we recommend it.

Treatment with a dose of 75 mg diclofenac once daily-if necessary with the additional use of paracetamol-is a favourable option for the postoperative care of THA.

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