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Inverse relation between Braak stage and cerebrovascular pathology in Alzheimer predominant dementia
  1. Ludwig Boltzmann Institute of Clinical Neurobiology, PKH/B-Building; Baumgartner Hoehe 1; A-1140 Vienna, Austriakurt.jellinger{at}

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    Goulding et al 1 carried out a preliminary retrospective postmortem analysis of 25 patients (13 men, 12 women, mean age 80.7 years) with the clinical diagnosis of Alzheimer-type dementia (only one with suspected multi-infarct dementia) and a 36.4% frequency of the ApoEε4 allele. Eighteen brains (89%) with neuritic Braak stage ⩽4 had either additional cerebrovascular lesions (n=14), or Lewy bodies (n=l), or both (n=6), with a significant inverse correlation between cerebrovascular lesions and Braak stage. Forty eight per cent of the brains showed small focal infarcts, and only 20% disclosed “pure” Alzheimer's disease pathology. No association between the ε4 allele and any pathological variable was found. Based on these data, the authors emphasised the importance of screening for concomitant pathology in Alzheimer's disease, in which a cerebrovascular component has been suggested as an additional pathogenic factor. These data can only in part be confirmed by personal experience in a cohort of 27 necropsy cases (13 men, 14 women) aged 77 to 91 (mean 85.9) years with the clinical diagnosis of degenerative dementia (possible or probable Alzheimer's disease) in 24, of vascular dementia in two, and Parkinson's+ Alzheimer's disease in one, studied between 1989 and 1998. Mini mental stages (n=14) ranged from 0 to 15 (mean 8.0); ApoE genotyping performed from paraffin blocks using a polymerase chain reaction (PCR) method disclosed the ε4 allele in 33%. In addition to the neuropathological evaluation criteria by Goulding et al 1 the NIA2 and CERAD criteria for Alzheimer's disease3 were used. The following data were obtained.

    The NIA criteria for Alzheimer's disease were positive in all but three cases diagnosed as senile dementia of the tangle type,4 44% staged CERAD A and 28% staged each CERAD B and C. Only 16/27 brains (59%) showed additional cerebrovascular lesions, either white matter changes alone (n=3) or in combination with lacunar state or small focal infarcts in the basal ganglia (n=13), or an old infarct in the area of the left posterior cerebral artery (n=1). Six of 27 (22%) showed additional subcortical (n=4) or both subcortical and cortical Lewy bodies, thus fitting the diagnostic criteria of dementia with Lewy bodies5 in two. Neuritic Braak stages 5 or 6 were present in 12 brains (44%), stage 4 in 14 (52%), and stage 2 in one (3%). Association with cerebrovascular lesions was seen in eight cases staged Braak 4 and 5 (or 5 and 6). When looking at the severity of the associated cerebrovascular lesions, severe ones (combined cerebrovascular disease II or III 1) were seen in seven brains with Braak stage 4 and in six staged Braak 5 (or 6), mild ones (cerebrovascular diaease 1) in one brain staged Braak 4, and in two with Braak stages 5 or 6. Carriers of the ApoE ε4 allele staged Braak 4 in five cases and Braak 5 in three, with additional cerebrovascular lesions in three brains each. Although in our small necropsy cohort, similar to that of Goulding et al,1 “pure” Alzheimer's disease was seen only in 22% (three cases each with Braak stages 4 and 5), in view of our data, the inverse relation between cerebrovascular disease and Alzheimer's disease, suggested by these authors, requires further confirmation in larger and possibly prospective clinicopathological case series.