18F-Flortaucipir in TDP-43 associated frontotemporal dementia.

Retention of 18F-Flortaucipir is reportedly increased in the semantic variant of primary progressive aphasia (svPPA), which is dominated by TDP-43 pathology. However, it is unclear if 18F-Flortaucipir is also increased in other TDP-43 diseases, such as bvFTD caused by a C9orf72 gene mutation. We therefore recruited six C9orf72 expansion carriers, six svPPA patients, and 54 healthy controls. All underwent 18F-Flortaucipir PET and MRI scanning. Data from 39 Alzheimer's Disease patients were used for comparison. PET tracer retention was assessed both at the region-of-interest (ROI) and at the voxel-level. Further, autoradiography using 3H-Flortaucipir was performed. SvPPA patients exhibited higher 18F-Flortaucipir retention in the lateral temporal cortex bilaterally according to ROI- and voxel-based analyses. In C9orf72 patients, 18F-Flortaucipir binding was slightly increased in the inferior frontal lobes in the ROI based analysis, but these results were not replicated in the voxel-based analysis. Autoradiography did not show specific binding in svPPA cases or in C9orf72-mutation carriers. In conclusion, temporal lobe 18F-Flortaucipir retention was observed in some cases of svPPA, but the uptake was of a lower magnitude compared to AD dementia. C9orf72-mutation carriers exhibited none or limited 18F-Flortaucipir retention, indicating that 18F-Flortaucipir binding in TDP-43 proteinopathies is not a general TDP-43 related phenomenon.

Subjective experience of memory deficits related to clinical and neuroimaging findings.

The aim of this study was to evaluate cognitive impairment, psychiatric symptoms and cerebral blood flow (CBF) patterns in middle-aged (35-64 years) and younger old patients (65-74 years) with subjective experience of memory deficits. The study group was heterogeneous with patients fulfilling criteria for dementia, as well as patients with mild cognitive impairment (MCI) and with non-verified cognitive impairment (non-MCI). Seventy per cent of the non-MCI patients reported long-lasting experiences of psychosocial stress tentatively causing the memory problems. The MCI patients were subdivided into two groups: MCI type 1 included patients with isolated memory impairment, while MCI type 2 included patients with memory impairment together with slight verbal and/or visuospatial impairments. CBF measurements comparing the two MCI groups with the non-MCI group were performed. The MCI type 2 showed reduced CBF in the left anterior medial temporal lobe as well as in parts of the posterior cingulate gyrus. The CBF pattern in MCI type 2 concurs with the pathophysiological process of Alzheimer's disease. The results indicate that it is important to make a subdivision of MCI patients regarding the presence of isolated memory impairments or memory impairments together with other slight cognitive deficits.