Structural imaging measures of brain aging

Abstract

During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily "normal" or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer's disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer's disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between "Normal" and "Healthy" brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society.

Fig. 1

Age specific prevalance of vascular risk factors and disease among the Framingham Offspring during 2004–2009. HTN hypertension, CAD coronary artery disease, CVA clinical stroke or TIA, AD Alzheimer’d disease

Fig. 2

Cross-sectional estimates of yearly differences in lobar brain volumes as a percentage of head size for men and woman of the Framingham Heart Study. Significant differences are seen for Frontal and Temporal lobar brain volumes, but not Parietal or Occipital

Fig. 3

Yearly rates of brain change among individuals of the UCD ADC who are cognitively normal. Colored regions reflect areas of significant yearly change. Darker colors reflect atrophy whereas warmer colors reflect expansion (e.g. CSF space enlargement)

Fig. 4

One example of white matter hyperintensities as seen on FLAIR imaging

Fig. 5

One example of an MRI infarct as seen on FLAIR imaging. The infarct is outlined by the circle on the image. The increased intensity surrounding the infarct is believed to reflect gliotic injury

Fig. 6

Prevalence of MRI infarction by decade of life among subjects of the Framingham Heart Study

Fig. 7

One example of extensive cerebral microbleeds as seen on gradient echo imaging

Fig. 8

Graphic summary of the multi-factorial relationships between age, genetics, vascular risk factors and Alzheimer’s disease that result in cerebral amyloid angiopathy (CAA) or cerebrovascular disease (CVD) that lead to cerebral microbleeds (CMB), white matter hyperintensities (WMH), infarction and brain atrophy all of which contribute to reduced cognitive ability