Gade, A., Skibinski, G., & Gydesen, S. Preclinical signs of impairment in persons at high risk of frontotemporal dementia related to chromosome 3 (FTD3): Preliminary findings in neuropsychological tests. Neurobiology of Aging 25[suppl. 2], S453. 2004.

Adr.: Department of Psychology, Copenhagen University; Memory Disorders Research Unit, Copenhagen University Hospital, Copenhagen, Denmark; and Frontotemporal Research in Jutland Association(FReJA)

Background
. We have studied a large kindred in Jutland with autosomal dominant frontotemporal dementia linked to chromosome 3, the only such family yet known (Gydesen et al., Neurology 2002, 59:1585-94). The early phenotype is not yet known, and we studied well subjects at risk of developing the disease to detect early signs. Methods. At risk subjects between 40 and 70 years of age and spouses were invited to participate in neuropsychological assessment performed without knowledge of status. 38 family members and 20 spouses participated. Some participants have not yet been haplotyped, and we report preliminary results from comparisons of 20 test measures in 3 groups of well-matched subjects: 11 high risk subjects, 16 low risk subjects, and 19 spouses. Results. T-tests without corrections for multiple comparisons showed: 1) No significant differences between the two control groups. 2) A total of 8 significant differences (p<.05; two p<.01) between high risk subjects and controls, all with high risk subjects impaired. Trail Making B was impaired relative to both control groups, and significant differences between high risk subjects and one control group (but not both) were found in cognitive estimations, letter-number sequencing (a measure of working memory control), design fluency, immediate (but not delayed) story recall, and one further test. Conclusion. This pattern of subtle impairment is indeed compatible with predominantly frontal involvement. We want to confirm these preliminary results in the full data set and replicate them in further cross-sectional and longitudinal analyses in a planned follow-up. At present, our results indicate that overt symptoms may be preceded by many years of subclinical impairment.