Callie Beck and Dr. Ramona O. Hopkins, Psychology
White-matter hyperintensities (WMHs) are unidentified bright objects in the white matter regions of the brain and have been observed on magnetic resonance (MR) brain images since the mid-1980s. Numerous studies have been conducted to determine the relationship between WMHs and various pathologic conditions such as hypertension, stroke, dementia, Alzheimer’s disease, brain atrophy, bipolar disorder, mania, depression, hemophilia, and following carbon monoxide poisoning. However, the etiology and mechanisms of WMHs remain unclear. A majority of the information regarding the prevalence of WMHs in normal healthy individuals comes from the control data in studies that focus on various illnesses such as bipolar disorder, depression, or mania. There are a relatively few studies that focus on normal individuals and the majority of those are older individuals or individuals with comorbid disorders.
Methods
In an effort to determine the relationship between age and WMHs, we assessed 243 healthy individuals from 16 to 65 years of age in our archival brain imaging data base (Blatter et al., 1995) for prevalence of WMHs in the periventricular and centrum semiovale regions on brain MR imaging using a semi-quantitative rating scale. Although there were no formal neurologic or neuropsychiatric examinations, all subjects answered a demographic and medical questionnaire and were excluded from the study if they had a prior history of head injury with loss of consciousness, neurological disorder, or alcohol or drug abuse. Periventricular WMHs (PVWMHs) and centrum semi-ovale WMHs (CSWMHs) were rated by comparing the subject’s MR images to sets of PVWMHs and CSWMHs standard images (Victoroff, Mack, Grafton, Schreiber, & Chui, 1994). A rating of 0 was assigned to images with no hyperintensities; 0.5 for WMHs less than or equal to standard #1; 1 for WMHs definitely more than image #1 and less than or equal to standard #2; and 2 for WMHs definitely greater than standard #2. Interrater reliability was established with a series of 29 scans and then applied to all scans in the study. In all cases interrater reliability (Pearson product-moment correlations) exceeded 0.9.
Results
We enrolled 243 healthy normal control subjects from age 16 to 65 years with a mean age of 37.0 ± 13.5 years. The prevalence of WMHs was 5.3%, with 3.7% of subjects having PVWMHs and 3.7% CSWMHs (Figure 1). The WMHs were small, a rating of 0.5 for all subjects except one subject who was 60 years of age who had WMHs ratings of 2 for both PVWMHs and CSWMHs (Figure 2). The median age for the subjects with no WMHs was 34.5 years and the median age for the subjects with WMHs was 57.0 years. Subjects that were older than 55 years had a 10 times increased prevalence of WMHs compared to subjects < 55 years [odds ratio = 10.01; 95% confidence interval 3.11 to 32.25; p < 0.001].
Conclusions
The strengths of our study include a large sample that assessed WMHs over 5 decades of life. The large age range of our sample allows us to evaluate the effect of age by decade. Our subjects were very healthy, and few had comorbid disorders. For a young, normal population WMHs are uncommon and when present are generally small (rating of 0.5). Our findings suggest that WMHs in healthy subjects are uncommon but increase with older age.
References:
- Blatter, D. D., Bigler, E. D., Gale, S. D., Johnson, S. C., Anderson, C. V., Burnett, B. M., et al. (1995). Quantitative volumetric analysis of brain MR: normative database spanning 5 decades of life. American Journal of Neuroradiology, 16(2), 241-251.
- Victoroff, J., Mack, W. J., Grafton, S. T., Schreiber, S. S., & Chui, H. C. (1994). A method to improve interrater reliability of visual inspection of brain MRI scans in dementia. Neurology, 44, 2267-2276.