Early Onset Alzheimer’s Disease Linked to Rapid Cognitive Decline

Psychol Med. 2009 Nov;39(11):1907-11. doi: 10.1017/S0033291709005492. Epub 2009 Apr 1.

Most rapid cognitive decline in APOE epsilon4 negative Alzheimer’s disease with early onset.

van der Vlies AE1, Koedam EL, Pijnenburg YA, Twisk JW, Scheltens P, van der Flier WM.



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.


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.


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 [beta (S.E.)=0.8 (0.5), p=0.14]. However, patients with early onset showed a faster decline on the MMSE [beta (S.E.)=2.4 (0.1) points/year] than those with late onset [beta (S.E.)=1.7 (0.1) points/year, p=0.00]. After stratification according to APOE genotype, APOE epsilon4 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 epsilon4 carriers, no difference in rate of cognitive decline was found between patients with early and late onset [beta (S.E.)=0.2 (0.2), p=0.47].


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 epsilon4 risk factor for AD.