Elderly cigarette smokers have an elevated risk of cognitive decline and neurological disease, however, the pathophysiological mechanisms are unclear. This study investigated which biological factors are responsible. 100 participants (age: 68±8 years, 69% male) with significant smoking history and range of respiratory and cardiovascular disease were recruited. Multiple linear regression showed that higher blood pressure, reduced respiratory function, hypoperfusion and biomarkers of cardiac (troponin T) damage and systemic inflammation (C-reactive protein) were associated with brain magnetic resonance markers of neurobiological damage and there may be complex interactions between them. Results support a vascular aetiology with contributions from systemic inflammation.