## 4 Discussion
Contrary to former studies, we found that the right hemisphere seems to be more affected by the disease than the left one in our AD cohort, although left-right asymmetry, especially of the hippocampus, receives less research attention [40]. A strength of this study is the fine segmentation for pASL perfusion data into 286 brain regions. FTD naturally shows frontotemporal patterns of hypoperfusion, which we could reproduce by a good positive correlation of volume and cerebral blood flow (STG, IFWMO) [41]. To the best of our knowledge, there are no other studies confirming reduced perfusion rates in atrophied thalami and the right EC in FTD patients so far. Thalamic atrophy, as discussed above, is a well-examined subject matter for FTD patients, so it is not surprising that we found reduced pASL perfusion rates. Loss of white matter microstructural integrity of the EC in FTD has been measured via DTI previously [42]. The clinical benefit of this particular finding, however, remains doubtful. On the one hand, our findings of a rather low correlation between volume and perfusion overall supports studies which have doubted the beneficial use of ASL in comparison to FDG-PET in the diagnosis of FTD [43; 44]. On the other hand, there are studies confirming a good correlation of ASL perfusion with FDG-PET [41; 45]. These conflicting findings could be best explained by the heterogeneity of relatively small sample populations and differing ASL techniques [46]. Our finding of a good correlation for volume loss in the IFO in MCI patients has not yet been discussed. Again, the clinical importance of this finding remains unclear, although degeneration or defects in the IFO (as described above) could produce severe symptoms. The fact that we did not find good correlation in the AD spectrum could be due to the lower sample size in that subgroup, as well as their mild clinical symptoms. Lastly, there is discussion around if atrophied brain regions may demonstrate paradox hypermetabolism and hyperperfusion as a last \"distress call\", especially in patients with MCI and AD [47]. As stated, our present study may be limited due to its small sample of participants, which might explain why we only found relatively few correlations of reduced CBF/rCBF with volume loss. Furthermore, there was no differentiation between subtypes of the FTD, MCI, and AD spectrum. Most of our AD patients were mildly affected (MMSE > 21) [48; 49; 50], which could explain the lack of a good correlation of hypoperfusion with atrophied brain regions, as well as the lack of atrophy in the parietal lobes. However, our results are in line with the formerly described atrophy patterns of other brain regions, the hippocampus being one of the earliest sites of pathological involvement, even in mild AD [34]. Image acquisition of pASL data in the elderly is sometimes difficult, as lacking cooperation and compliance during an MRI examination of cognitively impaired patients might lead to reduced image quality by motion artifacts. Yet, motion artifacts can be ruled out for structural MRI. There are hints that cerebral hypoperfusion precedes neurodegeneration in large population-based studies [51]. It has been suggested that lower perfusion is often attributed to neurodegeneration and can indicate neuronal dysfunction and synaptic failure. The first signs of neurodegeneration are likely to occur years before the diagnosis of dementia, and cerebral perfusion may consequently fall well before clinical symptoms of dementia arise. Unfortunately, we cannot deliver any answers to the question of whether reduced blood flow in certain brain regions leads to a decline in brain volume, or vice versa, volume loss and reduced metabolism leading to a downgrading of the need for blood supply. This would need longitudinal studies and was not the main subject matter of this study. The aim of our study was to compare brain perfusion patterns regarding hypoperfusion with sophisticated brain volumetric data regarding atrophy.