Stevens M, van Duijn C M, Kamphorst W, de Knijff P, Heutink P, van Gool W A, Scheltens P, Ravid R, Oostra B A, Niermeijer M F, van Swieten J C
Department of Neurology, University Hospital Rotterdam, The Netherlands.
Neurology. 1998 Jun;50(6):1541-5. doi: 10.1212/wnl.50.6.1541.
Frontotemporal dementia (FTD) is a common, non-Alzheimer's dementia. Its familial occurrence has been reported, but the frequency of positive family history is unknown.
We carried out a nationwide genetic-epidemiologic study of FTD in the Dutch population of 15 million people. The family history of dementia was analyzed in 74 FTD patients and 561 age- and gender-matched control subjects.
We found one or more first-degree relatives with dementia before age 80 in 38% (28 of 74) of FTD patients, but only in 15% (84 of 561) of control subjects. Ten percent of FTD patients had two or more first-degree relatives with dementia compared with 0.9% of the control subjects. Seven percent of FTD patients showed the ApoE4E4 genotype versus 2.3% of the control subjects. The first-degree relatives of FTD had a risk of 22% for dementia before age 80 compared with 11% in relatives of control subjects. The age of onset of dementia in affected first-degree relatives of FTD patients (60.9+/-10.6 years) was significantly lower than among affected relatives of control subjects (72.3+/-8.5 years). The first-degree relatives of FTD patients were 3.5 times (95% CI, 2.4 to 5.2) more at risk for developing dementia before age 80 than relatives of control subjects. The hazard ratio in the subgroup with unknown linkage to chromosome 17 was 2.4 (95% CI, 1.5 to 3.7).
This study documents the importance of genetic factors in a proportion of FTD patients with the age at onset of dementia in first-degree relatives being 11 years earlier than in the general population.
额颞叶痴呆（FTD）是一种常见的非阿尔茨海默病性痴呆。已有其家族性发病的报道，但阳性家族史的频率尚不清楚。
我们在荷兰1500万人口中开展了一项关于FTD的全国性遗传流行病学研究。对74例FTD患者和561例年龄及性别匹配的对照者的痴呆家族史进行了分析。
我们发现，38%（74例中的28例）的FTD患者有一名或多名80岁前患痴呆的一级亲属，而对照者中只有15%（561例中的84例）有。10%的FTD患者有两名或更多患痴呆的一级亲属，而对照者中这一比例为0.9%。7%的FTD患者表现为ApoE4E4基因型，而对照者中这一比例为2.3%。FTD患者的一级亲属在80岁前患痴呆的风险为22%，而对照者亲属的这一风险为11%。FTD患者受影响的一级亲属中痴呆的发病年龄（60.9±10.6岁）显著低于对照者受影响的亲属（72.3±8.5岁）。FTD患者的一级亲属在80岁前患痴呆的风险是对照者亲属的3.5倍（95%CI，2.4至5.2）。在与17号染色体连锁关系不明的亚组中，风险比为2.4（95%CI，1.5至3.7）。
本研究证明了遗传因素在一部分FTD患者中的重要性，其一级亲属中痴呆的发病年龄比一般人群早11年。
