There are distinct patterns of cognitive deficits differentiating the earlier and later disease stages in bvFTD, with the pattern of cognitive decline revealing in greater detail the natural history of the disease. These cognitive symptoms are readily apparent clinical markers of dysfunction in the principal brain networks known to undergo molecular and anatomical changes in bvFTD, thus are important indicators of the evolving pathology in individual patients.

Objective We investigated the viability of psychometrically robust executive function measures as markers for premanifest Huntington’s disease (HD). Methods Fifteen premanifest HD subjects and 42 controls were compared on the NIH EXAMINER executive function battery. This battery yields an overall Executive Composite score, plus Working Memory, Cognitive Control, and Fluency Scores that are measured on psychometrically matched scales. The scores were correlated with two disease markers, disease burden and striatal volumes, in the premanifest HD subjects. Results The premanifest HD subjects scored significantly lower on the Working Memory Score. The Executive Composite positively correlated with striatal volumes, and Working Memory Score negatively correlated with disease burden. The Cognitive Control and Fluency Scores did not differ between the groups or correlate significantly with the disease markers. Conclusions The NIH EXAMINER Executive Composite and Working Memory Score are sensitive markers of cognitive dysfunction, striatal volume, and disease burden in premanifest HD.