Abstract

Introduction: The loss of total brain volume (TBV) due to aging is associated with increasing ischemic white matter lesion volume (WMH) and dementia. Lower TBV may be secondary to chronic ischemia and hypoperfusion throughout the periventricular white matter rather than the burden of focal ischemia in the deep white matter. We hypothesized lower TBV would be more closely correlated with increasing periventricular white matter lesion volume (PV) rather than deep white matter lesion volume (DWMH). Methods: We enrolled 593 asymptomatic family members of probands with premature coronary artery disease (<60 years). DWMH, PV, and TBV were measured with 3Tesla MRI. Multivariate regression was completed for DWMH, PV, and TBV using volume change per age decade controlling for sex, race, diabetes, smoking currently, hypertension, obesity , and intracranial volume (ICV) for TBV, and a spline incorporated at age 54. Results: Participants were 58% women, 37% African-American, 29-74 years old. TBV/ICV was more correlated to PV than DWMH (correlation coefficients -0.26 and -0.11, p=<0.001 and 0.006). The PV was greater with older age 9%/decade until age 54 (95% CI 4-15%) and 24%/decade after age 54 (95% CI 1.6-3.2%). TBV was reduced with older age: 1.1 % smaller/decade until age 54 (95% CI -0.6 to -1.6) and 2.4% smaller/decade after (95% CI -1.6 to -3.1). For PV and TBV their age association changed significantly after age 54 (p=0.012, and 0.014). DWMH age association remained constant regardless of age. Conclusions: PV is more strongly correlated to TBV than DWMH and the age associated changes in PV and TBV were more similar to one another than DWMH. The association of increasing PV with lower TBV may help to explain the association of cognitive and motor decline with increasing PV. Future longitudinal studies are needed to verify this association.

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