In a large, national sample that was stroke-free and cognitively normal at baseline, followed for an average of 4 years, and culled of participants who developed clinical stroke in the interval, FSRP score, which is composed of vascular risk factors, was linearly related to rate of incident cognitive impairment. In the highest FSRP quartile (scores >11.99), almost 3 in 20 participants developed incident cognitive impairment during the follow-up.
All the elements of the FSRP are significant predictors of cognitive impairment individually, and the more individual risk factors a person has, the greater the risk of cognitive impairment. Age and presence of LVH were the only FSRP component factors independently associated with future development of cognitive impairment. The association between LVH and cognitive impairment remained after controlling for age, sex, race, region of residence, and education. Consistent with the notion that LVH is a late developing marker of long-term exposure to high blood pressure,27
we also found that high systolic blood pressure was related to incident cognitive impairment in persons without LVH. This suggests that hypertension may be a very important risk factor to address in order to prevent cognitive impairment. Overall, it appears that the total FSRP score and its components, while initially derived to predict stroke, are also useful in the prediction of cognitive impairment.
Other studies have shown that increased stroke risk as measured by total FSRP score is related to lowered cognitive performance cross-sectionally13,14
The longitudinal study28
consisted of 235 stroke- and dementia-free men at the baseline who were reassessed on a cognitive battery 3 years later. The FSRP was inversely related to verbal fluency but not word list learning, word list recall, pattern comparison, or digit span. Our study extends these findings by including a larger, more diverse population (23,752 participants, of whom 56% were female and 38% were African American), and longer follow-up (average of 4 and up to 6 years).
LVH is a pathologic reaction to cardiovascular disease including high blood pressure. Elevated blood pressure increases the load the heart contracts against and over time results in increased volume of heart muscle and functional degradation of the heart including heart failure. An earlier cross-sectional analysis of the Framingham Offspring Study cohort showed an inverse relation between left ventricular mass (as determined by heart wall thickness and chamber volume) and cognition.29
The relationship was attenuated when blood pressure was considered and eliminated when prevalent heart disease (coronary artery disease, claudication, and heart failure) and risk factors (diabetes, cholesterol, alcohol use, smoking, homocysteine, and depressed mood) were included in the modeling. Our study extends this finding by showing a longitudinal relationship between LVH and clinically significant incident cognitive impairment that is independent of other demographic and cardiovascular risk factors.
Our subgroup analysis suggested that elevations in systolic blood pressure were associated with incident cognitive impairment even in those without LVH. This is consistent with other studies of blood pressure and cognitive decline4,30,31
incident cognitive impairment,5–7
and incident dementia.9
Our data suggest an early role for elevated blood pressure in the relationship of LVH and longitudinal changes in cognition.
In contrast to other studies that reported a relationship of diabetes to cognitive decline,4,31–34
incident cognitive impairment,5,31–34
and incident dementia,8,10
diabetes was not independently associated with risk of incident cognitive impairment in this study (others have also failed to see an association35
). This may be due to a limitation of the SIS in assessing cognitive impairment as a recent systematic review of prospective observational studies on diabetes and cognitive decline indicated that the broad measure MMSE (from which the SIS is derived) was less sensitive than a psychomotor speed-based cognitive test for diabetes-associated cognitive decline.36
It is also possible that diabetes as reflected in the FSRP (present vs absent), while sensitive to stroke risk, requires additional elaboration and specification in order to be a marker of cognitive decline. For example, it may be necessary to capture the duration of exposure to diabetes or the quality of treatment and control of diabetes.
Subclinical cerebrovascular disease including white matter abnormalities, silent cerebral infarction, and brain atrophy may underlie the association we saw between stroke risk factors and cognition. Other studies with neuroimaging verification in stroke-free participants with FSRP risk have found that FSRP scores are correlated with silent cerebral infarctions37
and changes in cerebral brain volume over time.38
This study has strengths including a very large, diverse sample that was free of clinical stroke at the baseline, censoring subjects at the time of incident stroke during the follow-up interval, longitudinal analysis with moderate length of follow-up interval, and use of a robust marker of clinically important cognitive dysfunction. Limitations include attrition over the follow-up interval. The attrition rate in REGARDS is about 3% per year which is not atypical for a large study with high proportion of older adults. To the extent that less cognitively able subjects were over-represented among the dropouts, a likely situation,39
our findings would underestimate the relation between cardiovascular risk factors and cognition. Our use of a global cognitive marker focused on memory means that we are unable to examine the effects of stroke risk factors on other cognitive domains sensitive to cardiovascular dysfunction including executive, psychomotor, and visuospatial function. Our definition of cognitive impairment is based on a screening test and not a clinical diagnosis of mild cognitive impairment or dementia. While screening tests such as the SIS do have reasonable correspondence to clinical diagnosis,18,40
there is some loss of precision, which would make it less likely that correlates of cognitive impairment could be detected. We found that current smoking (as coded in the FSRP) was not related to cognitive status. Since relatively few people are current smokers and former smokers are common, future research could examine smoking in a more differentiated way, for example, current smoker, former smoker, or never smoked, or smoking could be scaled in terms of pack-years. Finally, 25% of our participants received a 7-lead ECG which requires calculation of Cornell voltage using S-wave amplitude in the midsternal lead (SV) instead of SV3 in the formula to calculate LVH. While this approach to LVH has demographic and clinical associations that are similar to that calculated from a standard 12-lead ECG (using SV3),26
some loss of precision in that portion of the sample is possible, which would lead to underestimation of the relationships between LVH and cognition.
Our findings suggest that the vascular risk factors measured by the FSRP, elevated blood pressure and its long-term consequence, left ventricular hypertrophy, may provide a simple and efficient means of identifying adults who are at risk for future cognitive impairment and lends support to the notion that increased attention to prevention and treatment of high blood pressure may be effective in preserving cognitive health.