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Most rapid cognitive decline in APOE ε4 negative Alzheimer's disease with early onset

Published online by Cambridge University Press:  01 April 2009

A. E. van der Vlies ,
E. L. G. E. Koedam ,
Y. A. L. Pijnenburg ,
J. W. R. Twisk ,
P. Scheltens  and
W. M. van der Flier
A. E. van der Vlies*
Affiliation:
Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands
E. L. G. E. Koedam
Affiliation:
Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands
Y. A. L. Pijnenburg
Affiliation:
Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands
J. W. R. Twisk
Affiliation:
Department of Clinical Epidemiology and Statistics, VU University Medical Centre, Amsterdam, The Netherlands
P. Scheltens
Affiliation:
Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands
W. M. van der Flier
Affiliation:
Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands
*
*Address for correspondence: A. E. van der Vlies, Department of Neurology and Alzheimer Centre, VU University Medical Centre, PO Box 7057, 1007 MBAmsterdam, The Netherlands. (Email: ae.vdvlies@vumc.nl)
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Abstract

Background

We aimed to compare the rate of cognitive decline in patients with early and late onset Alzheimer's disease (AD) and to investigate the potentially modifying influence of the apolipoprotein E (APOE) genotype.

Method

We included 99 patients with early onset AD (age ⩽65 years) and 192 patients with late onset AD (age >65 years) who had at least two scores on the Mini-Mental State Examination (MMSE) (range 2–14) obtained at least 1 year apart. Linear mixed models were performed to investigate the rate of cognitive decline dependent on age at onset (AAO) and APOE genotype.

Results

The mean (s.d.) age for patients with early onset AD was 57.7 (4.5) years, and 74.5 (5.1) years for patients with late onset AD. AAO was not associated with baseline MMSE [β (s.e.)=0.8 (0.5), p=0.14]. However, patients with early onset showed a faster decline on the MMSE [β (s.e.)=2.4 (0.1) points/year] than those with late onset [β (s.e.)=1.7 (0.1) points/year, p=0.00]. After stratification according to APOE genotype, APOE ε4 non-carriers with early onset showed faster cognitive decline than non-carriers with late onset [2.4 (0.3) v. 1.3 (0.3) points/year, p=0.01]. In APOE ε4 carriers, no difference in rate of cognitive decline was found between patients with early and late onset [β (s.e.)=0.2 (0.2), p=0.47].

Conclusion

Patients with early onset AD show more rapid cognitive decline than patients with late onset, suggesting that early onset AD follows a more aggressive course. Furthermore, this effect seems to be most prominent in patients with early onset who do not carry the genetic APOE ε4 risk factor for AD.

Keywords

AlzheimerAPOE genotypecognitionearly onsetpresenile
Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 11 , November 2009 , pp. 1907 - 1911
Copyright
Copyright © Cambridge University Press 2009

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