In this study, we found that several MR infarct characteristics were important to cognitive function: cortical infarcts and multiple infarcts in multiple regions were associated with increased odds of dementia. Cortical, multiple, or large infarcts were associated with lower global cognitive function (particularly lower perceptual speed) and memory function. Finally, the effect of MR infarcts on dementia and cognitive function did not vary by race or ethnicity.
Over the last decade, several clinical radiological studies have shown that cerebral infarcts noted on MRI increase the odds of dementia and these associations may depend on specific infarct characteristics such as number [3
], size, side [4
], or region [2
]. However, whether these associations are similar in the general population is largely unknown. Only two previous studies have examined this issue [3
]. The first study [3
] found that the presence of one or more large infarcts noted on MRI was associated with increased risk of dementia. Other infarct characteristics, such as location or anatomical side, were not examined. In the second study [37
], infarcts were present in 21% of the sample and were characterized based on their presence or absence, anatomical location, and size. The presence of infarcts noted in the baseline evaluation more than doubled the risk of having dementia and was associated with poor global cognitive performance. The results of this current study suggest that infarcts are associated with an increased risk of dementia and lowered cognitive function but also extend these findings in several important ways.
We found that cortical infarcts and multiple infarcts in multiple regions increased the odds of having dementia. Cortical infarcts are more likely to impair cognitive function due to their large size and the involvement of multiple areas of gray matter [4
]. In contrast to findings from clinical pathological studies that have shown that persons with lacunar infarcts (typically subcortical) were more likely to have dementia, or needed fewer plaques and tangles for a clinical diagnosis of AD [42
], we did not find an association between subcortical infarcts and odds of dementia or lowered cognitive function. Several factors could account for the discrepancies in results. A significant proportion of the sample was not demented, which may have limited the amount of coexisting AD pathology. Second, there was overlap between persons with cortical and subcortical infarcts. For instance, in our sample, only 32 of the 122 persons with subcortical infarcts had two or more infarcts, and only 10 of the 122 persons had small and large infarcts. Small numbers in some groups may have limited the ability to detect an association, making interpretation difficult.
The presence and region of additional infarcts may also have influenced the effect of subcortical infarcts. As reported by others [11
], multiple infarcts from multiple regions were linked to an increase in dementia and lowered cognitive function. This may suggest that not all subcortical infarcts are deleterious, but that a subgroup of persons with subcortical infarcts and with infarcts specifically in the cortex, brainstem, or cerebellum is susceptible to dementia and lowered cognitive function. Indeed, this may reflect more widespread and severe vascular disease. Whether these and other factors play a role in the association of subcortical infarcts (and cortical infarcts) with dementia will need to be explored in further studies with larger numbers.
Although infarcts were associated with lower function in a spectrum of cognitive domains, perceptual speed had the strongest and most consistent association with infarcts – a finding consistent with several clinical radiologic study results [46
]. Disruption of the prefrontal-subcortical loops may be involved, which can lead to impaired prefrontal lobe functioning and impaired information processing [49
]. Infarcts have also been associated with poor performance in episodic, semantic, and working memory, consistent with previous studies, suggesting that though the pattern and severity of cognitive impairment may differ, infarcts can mimic and compound some of the primary effects of AD pathology [51
Although studies have suggested that cerebrovascular disease and cerebral infarcts are more prevalent among African Americans [53
] and may play a larger role in the etiology of dementia within this racial group, in our sample, the association of infarcts with risk of dementia and lower cognitive function was similar among African Americans and Caucasians, suggesting that race/ethnicity alone does not modify the association of infarcts with cognitive function. Longitudinal assessment of cognitive function in relation to infarcts is needed to further examine these preliminary observations.
This study's strengths include a large well-characterized cohort of older blacks and whites, inclusion of dementia and continuous measures of global cognitive function, and specific cognitive systems in our analytic models. We conducted analyses with multiple cerebral infarct characteristics. When we explored combined characteristics, the group numbers decreased; thus, further study with larger sample sizes is necessary. Other limitations include the cross-sectional design and losses for MRI participation. In addition, the association of infarcts with other neuroimaging and biological markers relevant to dementia and cognitive function (e.g. white matter hyperintensities, hippocampus, infarct lesion volumes, and vascular factors) was not assessed and requires future study.