Background and purpose
Most of the neuropathological studies in brain aging were based on the assumption of a symmetric right-left hemisphere distribution of both Alzheimer's disease (AD) and vascular pathology. To explore the impact of asymmetric lesion formation on cognition, we performed a clinicopathological analysis of 153 cases with mixed pathology except macroinfarcts.
Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included assessment of Braak neurofibrillary tangle (NFT) and Aß-deposition staging, microvascular pathology and lacunes. The right-left hemisphere differences in neuropathological scores were evaluated using the Wilcoxon signed rank test. The relationship between the interhemispheric distribution of lesions and CDR scores was assessed using ordered logistic regression.
Unlike Braak NFT and Aß deposition staging, vascular scores were significantly higher in the left hemisphere for all CDR scores. A negative relationship was found between Braak NFT, but not Aß, staging and vascular scores in cases with moderate to severe dementia. In both hemispheres, Braak NFT staging was the main determinant of cognitive decline followed by vascular scores and Aß deposition staging. The concomitant predominance of AD and vascular pathology in the right hemisphere was associated with significantly higher CDR scores.
Our data show that the 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.