we have developed a mitochondrial activation therapy for AD with Coenzyme Q 1 0 , iron and vitamin B 6 . and demonstrated the relief of dementia in geneticailly-confirmed AD patient. Recently I have treated clinically diagnosed (DSM-IV) AD patients and found that patients with 2 apoE ε 4 alleles deteriorate rapidly after the thrapy is discontinued. In 27 patients (69.6+/-8.7 years old; range 49-88), I examined the effect of discontinued therapy after their informed consent. Mental status of the subjects was evaluated with a mini-mental state examination (MMS) and a functional assessment staging (FAST). I restarted the therapy once the mental status of the patients become measurably worse (5 points-down in MMS and/or 1 stage-down in FAST), or there were complaints from the patients' family members. After finishing the drug holiday, I examined the apoE phenotype of the patients by the isoelectric focusing/immunoblot. Subjects were divided into 4 groups on the phenotype of apoE; 2/3 (3 cases, 67.0+/-7.1 years old), 313 (11 cases, 66.8+/-9.2), 3/4 (7 cases, 75.3+/-8.5), and 4/4 (6 cases, 69.2+/-4.7) the duration of drug holiday in the 4/4 group was significantly shorter than that Of the other groups (p<0.01,unpaired t-test). There was no significant difference between 3/4 and 3/3 groups. The age, MMS score and FAST stage before the drug holiday were not significantly different between 4/4 and the other groups. The effect of the therapy before the drug holiday was also not significantly different between these groups. Thus, we consider that the numbers of apoE ε 4 alleles influence the progression of dementia in AD.