Abstract

There are at least 30 different mutations in the prion gene that cause clinical disease. Two of the most frequent in the UK are six octapeptide repeat insertion (6-OPRI) and P102L point mutation. We studied the neuropsychological profile of 18 symptomatic patients with the 6-OPRI and eight patients with the P102L mutations and in a subset correlated the deficits with cortical thickness estimates on brain MRI. We also recorded their premorbid the social functional, educational and occupational status. The 6-OPRI patients had marked premorbid social dysfunction, lower estimated premorbid IQ, and significantly lower educational attainment reflected in their adult occupations. In the symptomatic phase of the illness VIQ and PIQ were significantly lower in the 6-OPRI group. The 6-OPRI patients were significantly impaired in virtually all areas of cognition most apparent in executive function. In contrast executive function deficits were less common in the P102L group and function in other domains largely spared. Cortical thickness correlated with these deficits. It was significantly reduced in the posterior parietal, and parts of the occipital and frontal regions in the 6-|OPRI patients but not in the P102L patients. Significance of these findings will be discussed.