Although a variety of pathophysiological mechanisms have been postulated to account for the impact of CVD on cognitive function, investigations of these mechanisms have largely been cross-sectional and focused on individual mechanisms in isolation. Therefore, in this study, we undertook a concurrent examination of the contributions of several cardiac indices to longitudinal change in Attention-Executive-Psychomotor function among a cohort of geriatric patients with CVD. We found that lower CO, reduced variability in systolic BP, and increased variability in diastolic BP were the only predictors of prospective decline in Attention-Executive-Psychomotor function.
Our finding that patients with lower CO experienced a faster rate of decline in Attention-Executive-Psychomotor function than those with higher CO is consistent with prior cross-sectional studies that showed that circulatory insufficiency is associated with poorer cognitive function. For example, in a previous cross-sectional study, we found that ambulatory CVD patients with low CO exhibited selective impairments in cognitive measures of processing speed, cognitive flexibility, and problem solving.,9
It is possible that systemic hypoperfusion affects cognitive function because it engenders inadequate cerebral perfusion, cerebral hypoxia, and the disruption of vital white matter tracts.26–29
Indeed, there is indication that subcortical brain structures are particularly vulnerable to systemic and cerebral hypoperfusion, hence the characteristic “subcortical” cognitive profile seen in vascular disorders.30
Historically, studies of the relationship between BP and cognitive function in CVD have focused on mean BP perhaps because of the known association between hypertension and impaired cognition.31
However, there is growing evidence that while mean resting BP is an important factor, failure to consider other BP indices such as variability is a critical knowledge gap.17
Rothwell et al12
showed that measures of variability in systolic BP were strong predictors of stroke in large epidemiological cohorts independent of mean systolic BP, which was itself a weak predictor. Other studies by our research group have also shown that greater variability in systolic BP is associated with better cognitive function.8,20
. Although the finding of an association between reduced variability in systolic BP and decline in Attention-Executive-Psychomotor function might appear counterintuitive, it has plausible conceptual underpinnings.
There is an extensive literature suggesting that the capacity for autonomic reactivity is conducive to brain function. For instance, Cohen and Waters32
demonstrated that heart rate and skin conductance response during a levels-of-processing memory task was associated with the allocation of attentional effort during the tasks and also subsequent incidental recall. Other studies have shown that greater heart rate variability is indicative of greater vagal tone and is associated with better performance on measures of attention and working memory.33,34
Similar findings have been reported using measures of pupil dilation and skin conductance.35,36
Other studies have shown that older adults with restricted diurnal variation in BP exhibit cognitive deficits.37,38
Taken together, these findings suggest that variability in systolic BP might be beneficial, just as brachial artery reactivity to mechanical ischemia indicates healthy vascular endothelium. It is noteworthy that Rothwell et al12
showed that increased systolic BP variability was deleterious whereas we found it to be protective. Although the reasons for this discrepancy are not entirely clear, a few possibilities exist. For instance, their cohort was composed of hypertensive patients with a history of transient ischemic attack (TIA) or stroke, but no history of coronary artery disease. In contrast, our cohort consisted of older adults with a heterogeneous mix of CVD, including coronary artery disease. Furthermore, we explicitly excluded persons with history of stroke or TIA. It is plausible that the effect of systolic BP variability varies across patient populations, and outcome measures (eg, cognition, stroke, white matter lesions).12,19,20
In contrast to our finding with respect to variability in systolic BP, we found that increased variability in diastolic BP was predictive of decline in Attention-Executive-Psychomotor function. To our knowledge, this is the first time such a finding has been reported. While interesting, and perhaps in line with those studies that suggest that higher variability in BP is detrimental,12
we do not fully understand this finding. Nor is it clear why the effect of variability in diastolic BP is in the reverse direction of the effect of variability in systolic BP. Clearly, there is need for additional well-designed studies in this area.
It is worth noting that the participants in our study were all under the active care of a cardiologist, especially with respect to hypertension. It is plausible that a different pattern of findings might have emerged in a cohort with poorly controlled CVD. In addition, as already noted, our cohort consisted of a heterogeneous mix of older adults with various CVD. Although this makes our study more ecological valid (and, thus, potentially more generalizable) as cardiac patients rarely have isolated vascular diseases, it also limits the ability to understand how the effects of the cardiac indices we studied might differ across specific patient populations.
In summary, this prospective study examined the multivariable effects of several pathophysiological mechanisms on rate of decline in Attention-Executive-Psychomotor function among a cohort of ambulatory geriatric cardiac patients. We found that lower CO, reduced systolic BP variability, and increased diastolic BP variability at baseline were significant predictors of decline in Attention-Executive-Psychomotor function, pointing to the potential importance of cardiac function and systemic perfusion as determinants of CVD-associated cognitive dysfunction. Further studies would be needed to elucidate certain aspects of our findings, especially with respect to variability in diastolic BP.