Leukoaraiosis Severity Predicts Rate of Decline in Primary Progressive Aphasia

Aphasiology. 2020;34(3):365-375. doi: 10.1080/02687038.2019.1594152. Epub 2019 Mar 23.

Abstract

Background: The rate of decline in language in Primary Progressive Aphasia (PPA) is highly variable and difficult to predict at baseline. The severity of diffuse white matter disease (leukoaraiosis), a marker of overall brain health, may substantially influence the rate of decline.

Aims: To test the hypothesis that leukoaraiosis is associated with a steeper decline in naming in PPA.

Methods and procedures: In this longitudinal, observational study, 29 individuals with PPA (all variants) were administered the Boston Naming Test (BNT) at baseline and 1 year later. Two raters evaluated leukoaraiosis on baseline MRI, using the Cardiovascular Health Study scale. We evaluated the effects of leukoaraiosis severity, age, education, and baseline BNT on decline measured by change in BNT accuracy with multivariable linear regression. We also evaluated the effects of these variables on the dichotomized outcome of faster decline in BNT (worst 50%) versus slower decline (best 50%) using logistic regression.

Results: Together, leukoaraiosis, age, education, and baseline BNT score predicted change in BNT score (F(3, 25) = 8.12; p=0.0006). Change in BNT score was predicted by severity of leukoaraiosis (t =-3.81; p=0.001) and education (t= -2.45; p=0.022), independently of the other variables. When we dichotomized outcome into upper 50th percentile versus lower 50th percentile (faster decline), faster decline was predicted by all variables together (chi squared = 13.91; p = 0.008). However, only leukoaraiosis independently predicted outcome (OR=2.80; 95%CI: 1.11 to 7.03). For every 1 point increase on the CHS rating scale, there was 2.8 times higher chance of showing faster decline in naming.

Conclusion: Severity of leukoaraiosis is associated with steeper decline in naming in PPA. This imaging marker can aide in prognosis and planning by caregivers and stratification of participants in clinical trials.

Keywords: leukoaraiosis; primary progressive aphasia; prognosis; white matter disease.