First, cases with other central nervous system disorders (i.e., tumors, inflammation, Parkinson’s disease, Lewy body disease) were excluded from the present study (n = 194). predominance of AD and vascular pathology in the right hemisphere was associated with significantly higher CDR scores. == Conclusions == Our data show that this cognitive impact of AD and vascular lesions in mixed cases may be assessed unilaterally without major information loss. However, interhemispheric differences and, in particular, increased vascular and AD burden in the right hemisphere may increase the risk for dementia in this group. Keywords:Alzheimer, cerebral infarct, cognition, white matter disease == Introduction == Several clinicopathological studies postulated that the presence of cortical microinfarcts or lacunar infarcts significantly increase the risk for dementia among individuals with AD lesions1-5. The vascular burden in brain aging may, however, influence the extent of AD pathology without having a cognitive impactper se6. We recently reported that cortical microinfarcts and lacunes explained 15% of the presence of dementia in mixed cases without macroinfarcts and with various degrees of AD pathology7. One main limitation of this latter study was related to the use of a global bilateral microvascular score and assessment of AD pathology limited to the right hemisphere. We assess here the interhemispheric differences in AD and vascular lesion severity, relationships between AD and vascular burden in each hemisphere as well as possible cognitive impact of asymmetric lesion distribution in an independent series of prospectively studied patients with mixed pathology. == Materials and Methods == == Patients == The initial autopsy series included 1875 patients who died and were autopsied at the Geriatric and BCIP Psychiatric Hospitals of the University of Geneva during the period 1993-2006 (mean death rates: 7.5% and 1% respectively). All of the patients were referred to the hospital from the Geneva area and were older than 65 years of age. Permission for autopsy was systematically requested as part of the routine clinical work in both hospitals. Four criteria were used to define our sample. First, cases with other central nervous system disorders (i.e., tumors, inflammation, Parkinson’s disease, Lewy body disease) were excluded from the present study (n = 194). Second, all cases with macroscopic infarcts or non AD-related pathology were also excluded from the present series (n = BCIP 421). Similarly, cases with past history of psychiatric illnesses were not considered (n = 44). From the remaining 1216 cases, the final series included 153 right-handed patients aged 73 to 101 years assessed with the Clinical Dementia Rating Scale (CDR) at most three months prior to death (excluding cases with agonal says)8.(Table 1). == Table 1. == Demographic data and CDR scores in the entire sample. W, women; M, men. CDR, Clinical Dementia Rating score (0: no dementia, 0.5, questionable dementia, BCIP 1: mild dementia, 2: moderate dementia, 3: severe dementia). == Tissue processing == Lacunes in the white matter or basal ganglia and thalamus, were identified on macroscopic examination and controlled on Luxol-van Gieson (LVG) stained coronal sections. To visualize cortical microinfarcts as well as focal cortical and white matter gliosis, 1-cm-thick tissue blocks from the anterior hippocampus, inferior temporal, frontal, and parietal cortex bilaterally Rabbit Polyclonal to RBM34 were cut into 20-m-thick serial sections and stained with Globus silver impregnation7. To assess diffuse white matter and periventricular demyelination, 20-m-thick sections at the level of anterior commissure were stained with LVG. Additional 12-m-thick sections were processed bilaterally with antibodies to BCIP the tau and core amyloid proteins, -synuclein and ubiquitin7. All cases were classified neuropathologically according to the Braak NFT staging system9and amyloid nomenclature10. Lacunes, cortical microinfarcts and focal cortical gliosis were assessed in 10 sections per area using the following score:.