## 4 Discussion  
Prior studies suggest that certain atrophy patterns accompany hypoperfusion for different kinds of dementia, e.g., the prefrontal cortex, precuneus and hippocampal lobes in AD [10], and the thalami and reasonably the frontotemporal lobes in FTD [11]. Consequently, further reviews indicate, for example, hippocampal atrophy as a risk factor for progression to dementia in patients suffering from mild cognitive impairment (MCI) [12]--a prod prodromal state of AD. Sets of atrophy patterns might help to differentiate between different kinds of dementias, which sometimes are not easily diagnosed due to overlapping symptoms. For example, AD accounts for \(\sim\)30% of cases presenting with a clinical diagnosis of primary progressive aphasia (PPA) or behavioral-variant frontotemporal dementia (bvFTD) [13]. Accuracy of discrimination at an early or even asymptomatic state of dementia could support appropriate initial target-oriented medical care, e.g., medication with acetylcholinesterase-iniberts. We found a good correlation of formerly described atrophy patterns for FTD, MCI, and AD compared to CO. Consistently with the pathophysiology of FTD, we found significant brain atrophy in the frontotemporal brain structures of patients with FTD (MFG-DPFC,  
Figure 4: A patient with diagnosed FTD and corresponding pASL perfusion maps showing reduced CBF in the frontotemporal regions. From left to right: FLAIR Sequence, T1w Sequence, pASL Sequence; perfusion data were visualized with OLEA SPHERE® 2.3 (Olea medical, La Ciotat, France)(white arrows indicating regions of atrophy and hypoperfusion). IFGO, MFOG, RG, and STG) since frontotemporal lobar degeneration involves the deterioration of neurons in the gray matter of the frontotemporal lobes [14]. Volume reduction in IFG and STG--being classic language areas ([PERSON]'s and [PERSON]'s area)--is of great significance for FTD, especially in non-fluent-variant primary progressive aphasia (nfvPPA) and semantic-variant primary progressive aphasia (svPPA). Atrophy in the mesial temporal lobe is commonly seen in FTD patients [15]; in more detail, we could confirm amygdalar atrophy, which has been neuropathologically identified before [16]. The amygdala executes primary roles in the accumulation and formation of memories related to emotional events [17]; therefore, volume reduction of the amygdala might interfere with memory recall that is strengthened by emotion. Hippocampal atrophy is not solely specific for FTD and is rather pathognononic for AD [18], which makes hippocampal atrophy per se an uncertain imaging biomarker for FTD. As stated in prior studies, we can verify significant atrophy of the thalamus, which is a well-examined characteristic for the whole FTD spectrum [11; 19]. Thalamic as well as amygdalar atrophy in turn suggest a loss of cortical projection fibers, which might explain the reduced volume of the caudate tail, putamen, and globus pallidus--all of them connected to the thalamus via axonal pathways. Striatal degeneration in patients with FTD has been well demonstrated [20], explicitly with the putamen being associated with reinforcement learning and motor control, including articulation and speech [21]. Complementing these results, we found significant volume loss of the substantia nigra as an integral component of the basal ganglia circuitry for motor and limbic functions. Degeneration of the basal ganglia is a well-known aspect of neurodegenerative diseases, which might explain the progressive development of motor deficits in FTD patients, including parkinsonism and motor neuron diseases [15]. A number of studies found subcortical involvement in FTD patients confirming these findings [22; 23]. Hence, it is not surprising that we also found significant white matter-atrophy in the corona radiatia, cerebral peduncles, ECs and frontal brain regions (IFWMO, IFO), which contain descending (motor) nerve tracts and association fibers among others, alluding to an axonal degeneration as a consequence or as a precursor of (sub)cortical atrophy.