Background and Purpose- Patients with cardiovascular disease are at increased risk for cognitive decline. We studied the occurrence and profile of cognitive impairment in 3 patient groups as exemplar conditions of hemodynamic disturbances at different levels of the heart-brain axis, including patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (possible vascular cognitive impairment [VCI]). Methods- In 555 participants (160 HF, 107 COD, 160 possible VCI, 128 reference participants; 68±9 years; 36% F; Mini-Mental State Examination 28±2), we assessed cognitive functioning with a comprehensive test battery. Test scores were transformed into z-scores. Compound z-scores were constructed for: memory, language, attention/psychomotor speed, executive functioning, and global cognitive functioning. We rated cognitive domains as impaired when z-score≤-1.5. Based on the number of impaired domains, patients were classified as cognitively normal, minor, or major cognitive impairment. We used general linear models and χ2 tests to compare cognitive functioning between patient groups and the reference group. Results- Age, sex, and education adjusted global cognitive functioning z-score was lower in patients with COD (β [SE]=-0.46 [0.10], P<0.001) and possible VCI (β [SE]=-0.80 [0.09], P<0.001) compared with reference participants. On all domains, z-scores were lower in patients with COD and possible VCI compared with reference participants. Patients with HF had lower z-scores on attention/speed and language compared with reference participants. Cognitive impairment was observed in 18% of HF, 36% of COD, and 45% possible VCI. There was no difference in profile of impaired cognitive domains between patient groups. Memory and attention-psychomotor speed were most commonly affected, followed by executive functioning and language. Conclusions- A substantial part of patients with HF and COD had cognitive impairment, which warrants vigilance for the occurrence of cognitive impairment. These results underline the importance of an integrative approach in medicine in patients presenting with disorders in the heart-brain axis.