New insights into the cognitive profile of FTD mutation carriers

Can we identify individuals who carry a genetic mutation for FTD using simple clinical tests? With the advent of genetic testing, it is now possible to screen for genetic mutations in individuals and families who are at risk of developing FTD.

Approximately a third of people with FTD have a positive family history and the progranulin (GRN) gene has been identified as one of the most common causes of familial FTD. The changes in brain function in people with GRN, however, are highly variable. As such, it remains difficult to reliably predict how an individual with the GRN mutation will present on a clinical level.

A new study from FTD researchers in Canada, suggests that distinctive changes in thinking and brain function occur in individuals who carry the GRN genetic mutation, even before signs of dementia have emerged.

In this study, researchers explored changes in brain function using a large array of neuropsychological tests covering many aspects of cognition. Eight subjects in the study were carriers of the GRN mutation and their performance on the tasks was compared with 16 non-carriers, all of whom came from 6 different families with a known GRN mutation.

The researchers found that changes in visuospatial functioning (analyzing and understanding spatial relationships) and working memory (the ability to hold and manipulate information in mind) were present in GRN mutation carriers versus non-carriers.

This finding is important as it points to the presence of early changes in brain functioning in GRN mutation carriers, long before signs of frank dementia are present. The specific domains affected suggest that regions in the right hemisphere of the brain may be affected even in the presymptomatic stage of the disease.

Identifying potential changes in brain structure and function before an individual shows the hallmark symptoms of FTD represents an important avenue of research. By charting the disease course in more detail, it may be possible to refine the timing and delivery of disease-modifying therapeutics, which ultimately will prove beneficial for the individual and their family.


Hallam BJ, Jacova C, Hsiung GY, Wittenberg D, Sengdy P, Bouchard-Kerr P, Slack P, Rademakers R, Baker M, Chow TW, Levine B, Feldman HH, Mackenzie IR. Early Neuropsychological Characteristics of Progranulin Mutation Carriers. Journal of the International Neuropsychological Society. 2014 Jul 4. [Epub ahead of print]

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