Abstract
BACKGROUND: Three variants of primary progressive aphasia (PPA), distinguished by language performance and supportive patterns of atrophy on imaging, have different clinical courses and the prognoses for specific functions. For example, semantic variant PPA alone is distinguished by impaired word comprehension. However, sometimes individuals with high education show normal performance on word comprehension tests early on, making classification difficult. Furthermore, as the condition progresses, individuals with other variants develop word comprehension deficits and other behavioral symptoms, making distinctions between variants less clear. Longitudinal brain imaging allows identification of specific areas of atrophy in individual patients, which identifies the location of disease in each patient. AIMS: We hypothesized that the areas of atrophy in individual PPA participants would be closely correlated with decline in word comprehension over time. We propose that areas where tissue volume is correlated with word comprehension are areas that: (1) are essential for word comprehension, (2) compensate for word comprehension in some individuals with semantic variant PPA early in the course; and (3) show atrophy in individuals with logopenic and nonfluent variant PPA only late in the course. METHODS AND PROCEDURES: Fifteen participants with PPA (5 logopenic variant PPA; 8 semantic variant PPA; 2 nonfluent/agrammatic variant PPA; mean age 67.8), underwent high resolution MRI and cognitive tests at least 9 months apart. The correlations between change in regional volumes and change in auditory word comprehension scores were investigated using Spearman test. OUTCOMES & RESULTS: While scores on auditory word comprehension at Time 1 were correlated with volume loss in right and left temporal pole and left inferior temporal cortex (areas of atrophy associated with semantic variant PPA), deterioration in auditory word comprehension from Time 1 to Time 2 was associated with individual atrophy in left middle temporal cortex, left angular gyrus, and right inferior and middle temporal cortex. CONCLUSIONS: Progressive atrophy in focal areas surrounding left temporal pole and left inferior temporal cortex, and right homologous area is closely related to progressive decline in auditory word comprehension. These correlations likely reflect areas that help support auditory word comprehension, effectively compensating for subtle deficits in some individuals early in the course of semantic variant PPA, as well as areas that are critical for auditory word comprehension that eventually atrophy in individuals with other variants of PPA. Individual patterns of atrophy also help us understand and predict the clinical course of individuals, such as associated behavioral or motor deficits.