Hereditary fronto-temporal dementia linked to chromosome 17q21-22 (FTDP-17) is caused in most, but not all, families by mutations in the tau gene. FTD patients with and without a positive family history (dementia in first-degree relatives) were investigated in a genetic-epidemiological study in the Netherlands by means of a neuropsychological evaluation and brain imaging. We have ascertained 245 patients in this study. Tau screening was carried out in 154 (63%) out of 245 patients. Thirty-one patients had mutations in the tau gene: P301L in 18, G272V in 4, R406W in 4, L315R in 5 patients, and S320F and DK280 in 1 patient both. Neuropsychological data became available in 30 patients. Wordfinding difficulties were mentioned in 15 (50%) patients, and forgetfulness in 6 (20%) patients. Spontaneous speech decreased progressively over time in all patients. Neuropsychological evalaution showed deficits in naming in 67%, and of comprehension in 24%. Impairment in proverbs was an early feature, and was present in 90 percent. Decreased verbal fluency, paraphasias and perseverations were often found (63, 45 and 56 percent). Patients had often mild deficits in verbal and visual memory tests (58 and 50 percent). Visuo-constructive functions remained intact in nearly all patients (84 percent).

Testing FTDP-17 patients in different stages of the disease revealed a characteristic pattern of progression, starting with deficits in naming and abstractive thinking, followed by impairment in attention and concentration, mild memory problems, perseverations and paraphasias. The pattern of cerebral atrophy was frontotemporal in 50 percent (20% asymmetric), and predominantly temporal in another 40 percent (17% asymmetric). Our conclusion is that FTDP-17 patients showed a characteristic profile in cognitive deterioration over time.