The aim of this work is to examine the association of probable Alzheimer and vascular dementias with blood levels of homocysteine, and its biological determinants folate and vitamin B12, in addition to its impact on the severity of neurocognitive impairment and radiological brain atrophic changes in these dementing disorders.The current study included eighteen right handed patients; including ten females and eight males of mean age ± SD 70.4± 3.65 years, 13 illiterates; with clinically probable DAT diagnosed according to the criteria of National Institute of Neurological and Communicative Disorders and Alzheimer Disease and Related Disorders Association (NINCDS ADARDA), with Hachniski Ischemic Score (HIS) < 4 and dementia duration ranging from 1 to 5 years; and twenty two right handed patients; including ten females, twelve males with mean age ± SD 71.1± 3.2 years, 16 illiterates; with clinically probable VaD diagnosed according to the criteria of National Institute of Neurological Disorders and Stroke and Association Internationale Pour la Recherche et l’Enseignement en Neurosciences (NINCD-AIREN) with HIS > 7 and dementia duration ranging from 1 to 5 years in addition to 20 age, sex and educationally matched right handed healthy normal controls; including ten females and ten males of mean age ± SD 70.7 ± 3.1 years and 15 illiterates. They were subjected to thorough history taking; routine general and neurological examination; neuropsychiatric assessment (MMSE, HIS and GDS), brain CT scan, MRI and MRA in addition to laboratory investigation especially for serum tHcy, folate and vitamin B12 levels. The results were tabulated, statistically analyzed and summarized as follows:There was no significant difference regarding age, gender and education among VaD, DAT patients and the controls. A positive family history of dementia was significantly higher in DAT patients compared with those of VaD (P = 0.046). Although there was no significant difference in the level of education among all groups, the incidence of illiteracy was relatively high (72.7% & 72.2% and 75% respectively).It could be noticed that vascular risk factors were commonly reported in VaD and DAT patients (diabetes mellitus 22.7% & 22.2%, cardio-vascular disease 31.8% & 27.8%, smoking 27.3% & 16.7%, hypertension 100% & 44.4%, hyprcholesterolaemia 22.7% & 22.2%). There was no significant difference between the two groups regarding these vascular risk factors except hypertension and history of major stroke and transient ischemic attacks which were significantly higher in VaD patients compared with DAT patients (P < 0.001 & = 0.002 & = 0.016 respectively).No significant difference between VaD and DAT patients regarding the disturbance of their memory (P = 1.0), attention (P = 1.0), abstract thinking (P = 0.6) and judgment abilities (P = 0.5) was observed. However, the mood and calculation abilities were more significantly affected in VaD patients (P = 0.04 & 0.03 respectively).The duration of dementia was significantly correlated with the severity of cognitive impairment judged by lower MMSE score (P < 0.01) however the relation did not reach a significant value with the GDS score (P > 0.05).There was no significant difference in the mean minimum thickness of MTL, FI or V3 between the DAT and VaD patients (P = 0.55, 0.93 & 0.89 respectively).The mean minimum thickness of MTL in patients with VaD (mean 8.8 ± 2.38 mm, range “5-13” mm) and in those with DAT (mean 8.2 ± 2.36 mm, range “4-12” mm) was significantly less than the controls (mean 15.15 ± 1.98, range “11-18” mm) (P < 0.001). In addition, the CT scan measured indicies of ventricular volume (FI & V3) were significantly higher in VaD and DAT patients compared with the controls (P < 0.001 & < 0.001 respectively).There was a highly significant statistical difference between the total patients group and the control regarding MTL, FI, V3 (P < 0.001 & < 0.001 & <0.001 respectively).MRI measured mean hippocompal volume was significantly higher in VaD patients (1.76 ± 0.23) compared with DAT patients (1.47 ± 0.24) (P < 0.001). However, the difference in the MRI measured mean ventricular volume in VaD patients (62.4 ± 6.5) did not reach a significant level in comparison with those of DAT patients (59.8 ± 5.8) (P = 0.18).The control group had significantly larger mean hippocompal volume (2.44 ± 0.53) compared with VaD (1.76 ± 0.23) & DAT (1.47 ± 0.24) Pts (P < 0.001). Also the control group had significantly smaller mean MRI measured ventricular volume (29.2 ± 4.7) compared with VaD (62.4 ± 6.5) and DAT (59.8 ± 5.8) patients (P < 0.001).There was a highly significant statistical difference between the total patients groups and the control regarding HV & VV (P < 0.001 & < 0.001 respectively).The radiological evidence of extensive (grade 3 & 4) leukoaraiosis was significantly higher in patients with VaD compared with DAT (P = 0.02). Furthermore DAT patients with leukoaraiosis (55.6%) had only (grade 1 & 2) severity.The duration of dementia was significantly correlated with CT scan global indices of brain atrophy (FI & V3) (P < 0.05 & < 0.05).In VaD patients the severity of cognitive impairment judged by lower MMSE score and higher GDS score was significantly correlated with multiplicity of the lesions (P = 0.013 & P = 0.005) and side of the lesion (bilateral “P = 0.007 & P = 0.01”). However, no significant correlation could be detected between the severity of cognitive impairment and the site of the lesion (P = 0.28 & P = 0.6) and location of the lesion (P = 0.3 & P = 0.59).The severity of brain atrophic changes was significantly correlated with the severity of cognitive impairment judged by lower MMSE score (P < 0.001 & P < 0.05) and higher GDS score (P < 0.001 & < 0.05 VaD and DAT patients respectively).The severity of leukoaraosis was significantly correlated with the severity of cognitive impairment judged by lower MMSE score (P < 0.05) and higher GDS score (P < 0.05). Also, the severity of leukoararosis was highly significantly correlated with both MRI measured larger ventricular volume (P < 0.001) and smaller hipocampal volume (P < 0.01).There was a highly significant statistical difference between VaD patients and the controls & DAT patients and the controls regarding serum tHcy, folate and vitamin B12 (P < 0.001 & < 0.001 respectively) in the mentioned groups.Serum tHcy level was found to be significantly higher in VaD and DAT patients compared with the control (P < 0.001) while serum folate and vitamin B12 level were significantly lower in VaD and DAT patients compared with the controls (P < 0.001).There was a highly significant statistical difference between total patients group and the controls regarding serum tHyc, folate and vitamin B12 (P <0.001).There was no significant statistical difference between VaD and DAT patients regarding serum tHcy, folate and vitamin B12 (P = 0.91 & 0.2 & 0.9 respectively).The duration of dementia was significantly correlated positively with high serum tHcy and negatively with lower B12 levels (P < 0.05 & < 0.05) but the relation did not reach a significant level with serum folate (P > 0.05).A highly significant correlation was found between lower MMSE score & higher GDS score and higher serum tHcy levels (P < 0.001) & lower serum folate and B12 levels (P < 0.001 & < 0.01) in patients groups.The statistical relation between serum tHcy level and the severity of cerebral atherosclerosis as detected in the MRA brain in both VaD and DAT patients revealed a highly significant association between the elevated serum tHcy level and the angiographic evidence of positive cerebral atherosclerosis (MRA with 2 or more stenotic sites) in patients with VaD and DAT (P < 0.005 & < 0.001 respectively).The severity of radiological global brain atrophic changes was persistently significantly correlated with the elevation of serum tHcy in VaD and DAT patients (P < 0.05 & < 0.001) respectively rather than the reduction of serum folate (which shows significant correlation in VaD patients “P < 0.05” but not in DAT patients “P > 0.05”) and the reduction of vitamin B12 level (which shows non significant correlation in VaD patients “P > 0.05” and a significant correlation in DAT patients “P < 0.01”).The severity of leukoaraiosis was significantly correlated with higher serum tHcy level (P < 0.001) and lower folate (P < 0.001) and vit. B12 level (P < 0.001) in VaD and DAT patients.CONCLUSIONS:* Dementia is a common and devastating major public health problem.* The vascular risk factors, traditionally regarded as a distinguishing criteria between VaD and DAT, have been shown to be also associated with DAT.* Vascular dementia and dementia of Alzheimer type “the two most common types of dementia” are both associated with elevation of blood homocysteine level and reduction of its biological determinant folate and vitamin B12 levels.* Hyperhomocysteinaemia in these dementing disorders (VaD & DAT) is correlated with the severity of both cognitive impairment as well as radiological brain atrophic changes.* Brain MRI with its better regional anatomical resolution than CT scan, is of value not only in the diagnosis of dementia but also in the differential diagnosis of its types, however, CT scan is easier, cheaper, more widely available and most importantly, is much less distressing to dementia patients.* Vascular dementia is commonly associated with bilateral lesions, multiple and larger lesions as well as extensive white matter lesions, however, the usefulness of “heterogenous” VaD as a diagnostic category is questionable.* The radiological findings of leukoaraiosis is not only assiociated with VaD but also with DAT, however, it is more severe in VaD than DAT patients.* The demonstration of vascular risk factors, hyperhomocysteinaemia, radiological global brain atrophic changes and leukoaraiosis in both VaD and DAT patients, points to a substantial overlap between these dementing disorders which suggest that “vascular pathology”, the traditional cornerstone of the differential diagnosis, may not represent a clear line of demarcation as originally thought.RECOMMENDATIONS:* Homocysteine is an intriguing amino-acid that will continue to excite neuropsychological researches.* Homocysteine as a functional marker of B vitamin status in the tissues, represents growing area of interest in the neurochemical evaluation of VaD and DAT patients with its possible application in the early diagnosis of dementia even at a preclinical stage. Furthermore, future determination of the correlation between blood homocysteine level with oxidative stress and immune activation markers during different stages of progression of these dementing disorders, could provide further insight to the role of homocysteine in their pathogenesis.* Large scale double blind and placebo controlled clinical trials in high risk population are needed to determine whether lowering blood homocysteine level would reduce the risk of VaD and DAT.* Modified criteria are required to specify the etiology of heterogenous “VaD” as a part of the diagnostic formulation.* Future longitudinal large scale studies are needed to compare the evolution of VaD and DAT during different stages of disease progression.* With the hope to minimize the burden of dementia, one challenge is to develop major public health strategies affecting large populations for the modification of the vascular and demographic risk factors in the early and midlife. Another challenge, is the need to move toward identifying the cognitive impairment at an earlier stage before the development of dementia.* The convergence of VaD and DAT (neurochemically, epidemiologically, clinically and radiologically) provides a potential framework for an improved understanding of the pathogenesis of such dementing disorders and offers some promise toward the search for preventive and therapeutic strategies.