Psychological Medicine

Original Articles

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

A. E. van der Vliesa1 c1, E. L. G. E. Koedama1, Y. A. L. Pijnenburga1, J. W. R. Twiska2, P. Scheltensa1 and W. M. van der Fliera1

a1 Department of Neurology and Alzheimer Centre, VU University Medical Centre, Amsterdam, The Netherlands

a2 Department of Clinical Epidemiology and Statistics, VU University Medical Centre, Amsterdam, The Netherlands


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.

(Received February 22 2008)

(Revised February 09 2009)

(Accepted February 09 2009)

(Online publication April 01 2009)