LAUSR

We read with great interest the articles by Nedelska and colleagues showing significantly larger amounts of tau deposition in posterior cortical atrophy (PCA) than in dementia with Lewy bodies (DLB) as seen by AV-1451 PET. This finding could contribute tomore accurate differential diagnosis of PCA and DLB, as currently many biomarkers such as glucose metabolism and perfusion distribution in PCA and DLB have similar characteristics including the cingulate island sign (CIS), which is a term for the phenomenon seen in PCA and DLB in which metabolic capability in the posterior cingulate cortex (PCC) is spared relative to the precuneus plus cuneus. Moreover, these findings have implications in terms of the biological understanding of CIS, which is now a supportive biomarker of DLB, namely, what CIS reflects. Glucose metabolism/perfusion in PCC is preserved in DLB, whereas it decreases first in typical Alzheimer’s disease (AD). The proposed pathogenesis of CIS has been refined several times since it was first described. First, CIS was associated with the lower Braak neurofibrillary tangle (NFT) stage. We confirmed this in a previous study through the significant correlation between CIS ratio and medial temporal lobe (MTL) atrophy. Then, Whitwell et al suggested a revision of the origin of CIS to the “sparing of posterior limbic circuitry” based on our previous finding and the fact that PCA subjects often have an unusual distribution of NFT with relative sparing of the hippocampus. The preservation of posterior limbic circuitry in both PCA and DLB could be confirmed by tau PET if Whitwell’s hypothesis is correct. Nedelska et al showed that some patients with PCA and DLB seemed to show sparing of the MTL. However, almost all the regions in the brain including the MTL showed a significant difference in tau deposition. One possible explanation could be that not all PCA and DLB patients show CIS. Low prevalence of CIS-presenting patients in PCA may explain the high accumulation of tau tracer. Having considered these, we would like to further refine the interpretation of CIS to include preservation of the medial cholinergic pathway. This provides another potential cause for the diaschisis of the PCC other than MTL, although we believe that changes in the MTL invariably contribute to PCC hypometabolism/hypoperfusion. We demonstrated that an acetylcholine esterase inhibitor temporally restored the hypoperfusion in PCC of mild AD patients, suggesting that cholinergic neurons projecting from the nucleus basalis Meynert may play an important role in PCC hypoperfusion in AD. The straight gyrus, medial orbitofrontal cortex, and anterior cingulate cortex, which are located on the medial cholinergic pathway that runs from the nucleus basalis Meynert to the PCC, showed the least accumulation of tau in PCA.