To evaluate the differential diagnostic role of apolipoprotein E (apoE) genotype in dementia, we carried out a meta- analysis of 78 case-control series, including our own new data. The dementia subjects were grouped into Alzheimer's disease (AD) and non-AD. AD patients were subgrouped according to their subtypes, and non-AD patients into vascular dementia (VD), mixed dementia (MD), and non-AD non-VD dementia (NAVD). The apoE allele frequencies and apoE genotype-specific odds ratio (OR) of each group were estimated. The (4 allele frequency was higher in all of the dementia subgroups than in the elderly controls, and the associations with (4 allele were lower in the non-AD (OR 1.8) patients than in the AD (OR 4.2) patients. However, the apoE-related risk alsovaried as a function of the subgroup, in both the AD and non-AD groups; for AD, it was dependent on the subtype of AD (OR 2.3 - 11.3), and higher in late- onset and familial cases than in early-onset and sporadic cases, respectively; among non-AD patients, it was higher in MD (OR 2.6) than in VD (OR 1.3), and intermediate in NAVD (OR 1.9), in which a significant difference was also found between Lewy body dementia (LBD) type (OR 5.1) and non-LBD type (OR 1.3). In conclusion, variability in the apoE-related risk was found in both the AD and non-AD cases, depending on the subgroup. Therefore, precise subgrouping of both AD and non-AD patients should be performed, and this information should taken into consideration when interpreting the results of apoE genotyping.