Presymptomatic semantic impairment in a case of fronto–temporal lobar degeneration associated with the +16 mutation in MAPT

Abstract

We describe a patient who came to neurological attention because of his at-risk status for the +16 exon 10 splice mutation in the tau gene (microtubule associated protein tau, MAPT), which had given rise to progressive behavioural disturbances in two of his siblings. The patient began to exhibit early signs of behavioural disturbance at around the age of symptom onset in both of his siblings. Although he did not spontaneously complain of difficulties in the domain of language, he met clinical, radiological and neuropsychological criteria for semantic dementia. On the assumption that his illness is mediated by the same pathological process as those of his siblings, we propose that this clinical picture represents the earliest changes of a semantic impairment - a phase of the illness that is often retrospectively described by patients and their relations, but has never previously been documented at first hand. Although typical of semantic dementia in many respects, the illness had several interesting and atypical features that emerged on detailed testing: first, he exhibited no insight into his difficulties; secondly, progression over a twelve-month interval was unusually slow; thirdly, he evinced a striking and consistent advantage for nonliving over living concepts; fourthly, a differential impairment of distinctive over shared knowledge did not emerge except when items that he could still name were compared with those for which he was anomic. Finally, the availability of post mortem pathological analysis from the brains of both of his affected siblings allowed us to attribute his illness to a specific pathological process which is considered unusual for patients with this clinical phenotype.

Acknowledgments

The work reported here was funded by a Medical Research Council Clinician Scientist Fellowship award to PG. We are indebted to the subject and his wife for the time and effort they so generously devoted to the study.