Familial aggregation in frontotemporal dementia.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Stevens
M
M
Department of Neurology, University Hospital Rotterdam, The Netherlands.
van Duijn
C M
CM
Kamphorst
W
W
de Knijff
P
P
Heutink
P
P
van Gool
W A
WA
Scheltens
P
P
Ravid
R
R
Oostra
B A
BA
Niermeijer
M F
MF
van Swieten
J C
JC
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003704:Dementia / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D013702:Temporal Lobe / Q000503:physiopathology*
D001057:Apolipoproteins E