brain at autopsy typically are the only definitive diagnosis of the disease. We did not observe an association between the ACE-ID polymorphism and DAT or ARCD in the elderly Arab population of Wadi Ara. Notably, inherited susceptibility for DAT in Wadi Ara is also not accounted for by the ApoE ε4 allele. Indeed, the frequency of ApoE ε4 among DAT, ARCD, and control was 0.027, 0.033, and 0.029, respectively (Bowirrat et al 2000). Nonetheless, the relationship between ACE and AD is controversial. Several studies have implicated the ID polymorphism and risk of AD (Narain et al 2000; Cheng et al 2002; Kehoe et al 2003; Elkins et al 2004; Tian et al 2004), while other studies failed to find an association (Myllykangas et al 2000; Taylor et al 2001; Buss et al 2002; Lendon et al 2002; Monastero et al 2002; Harrap et al 2003; Panza et al 2003). Moreover, the pattern of association has been confusing, with some studies showing an association with the I allele (Alvarez et al 1999; Yang et al 2000; Hu et al 2001), while others with the D allele (Amouyel et al 1996; Palumbo et al 1999; Crawford et al 2000; Farrer et al 2000; Richard et al 2001). The reasons for the disparity in results across studies may be due to differences in ethnic background, different environmental factors, or subject misclassification. To date, few studies have examined the frequency of the ACE genotypes in autopsy-confirmed cases of AD, or investigated the potential effect of these ACE genotypes on the pathology of the disorder. In one autopsy series, the ACE genotype was not associated with the amount of Aβ40, Aβ42, or pathological tau protein deposited within the frontal cortex, or in the extent of amyloid angiopathy in the brain, whether ApoE ε4 allele was present or not (Lendon et al 2002). The only other autopsy-based study of ACE (based on an elderly Finnish population) also failed to detect an association with ACE (Myllykangas et al 2000). In the Arab community, autopsy is prohibited for religious and traditional reasons. Other limitations of our study are the absence of biomarkers and complete biochemical examinations, and the low number of neuroimaging performed. These helpful clinical techniques are necessary to improve our clinical diagnosis of DAT and are required to differentiate it from similar clinical manifestation that mimic the presentation of dementia. A possible biological explanation for an association between ACE and AD is still unclear. The insertion allele appears to reduce ACE expression, and DD homozygotes and ID heterozygotes have more circulating ACE than II Neuropsychiatric Disease and Treatment 2005:1(1) ACE and dementia in Arab population homozygotes: 65%, and 31%, respectively (Rieder et al 1999). This increased activity of the D allele may alter Aβ deposition by a direct proteolytic mechanism (Kehoe et al 2003). Alternatively, ACE may have an indirect role in the progression of AD. The ID polymorphism has also been implicated in various conditions including hypertension (Zaman et al 2002; Hopkins and Hunt 2003), coronary heart disease (Arbustini et al 1995; Kauma et al 1996), cardiomyopathy (Pfohl et al 1998), stroke (de la Torre et al 2002), and juvenile rheumatoid arthritis (Alsaeid et al 2003). Other studies don’t confirm these associations (see Ueda et al 1995; Hung et al 1999; Harrap et al 2003). Several studies suggest that there may be a relationship between cardiovascular lesions and the severity and progression of AD (Snowdon et al 1997; Zuliani et al 2001; Bowirrat, Friedland, Korczyn 2002; de la Torre 2002; Korczyn 2002). In summary, in the present study, we found a lack of association between ACE and DAT. Our previous studies have not determined any gene that may explain the high prevalence of DAT in this community, but we have found high prevalence of vascular dementia (VaD) following stroke. Indeed, the prevalence of VaD constitutes 5.9% of the total elderly Arab population in Wadi Ara and about 22% of the total dementia population (Bowirrat, Friedland, Korczyn 2002). This prevalence of VaD (22%) is extremely high compared with VaD patients who accounted for only 6% of all dementia patients identified by Fillit and Hill (2002). Given the role of the ACE gene in vascular disease as well as in AD, the ability to detect association with AD may be complex. On the other hand, and in light of the high frequency of VaD in this population, a new study to evaluate the role of ACE in VaD is essential. Acknowledgments This work was supported in part by grants from the National Institute of Health (U01-AG17173), the Institute for the Study of Aging, NIAAA (R37-AA07112), and the US Department of Veterans Affairs. References Alsaeid K, Haider MZ, Ayoub EM. 2003. Angiotensin converting enzyme gene insertion-deletion polymorphism is associated with juvenile rheumatoid arthritis. J Rheumatol, 30:2705–9. Alvarez R, Alvarez V, Lahoz CH, et al. 1999. Angiotensin converting enzyme and endothelial nitric oxide synthase DNA polymorphisms and late onset Alzheimer’s disease. J Neurol Neurosurg Psychiatry, 67:733–6. Amouyel P, Richard F, Cottel D, et al. 1996. The deletion allele of the angiotensin I converting enzyme gene as a genetic susceptibility factor for cognitive impairment. Neurosci Lett, 217:203–5. 75