Only one case of the corticobasal syndrome phenotype [33] has been reported in c9FTD/ALS [16]. Though rare, the amnestic presentation Sutent diagnosed clinically as probable Alzheimer’s disease has been observed across many in the series [20,21,25,26], including one analysis focused on late-onset Alzheimer’s disease [34]. The phenotype of dementia with Lewy bodies was reported in a few cases in one series [20]. These observations suggest that the C9ORF72 mutation can manifest as a variety of dementia phenotypes as well as pure ALS, but the vast majority have the core syndrome of bvFTD ?? parkinsonism ?? ALS. Cognitive features The classic bvFTD phenotype involves executive dysfunction and word retrieval difficulties with relative sparing of memory and visuospatial functioning [31,32], as exemplified by our illustrative case.

Degeneration of the dorsomedial and dorsolateral cortices and their afferent and efferent connections – two of the critical frontosubcortical neural networks involved in executive functioning, word retrieval, psychomotor speed, motivation, and so on – is the likely substrate underlying the typical bvFTD cognitive features. In some c9FTD/ALS cases, this classic phenotype is not always exhibited, owing mainly to memory being impaired [20,21,25-28]. Visuo-spatial dysfunction is present in a minority of cases [21,25-28]. In addition to bifrontal and cingulate cortex atrophy, parietal cortex atrophy is part of the signature pattern on MRI [35] and this likely explains visuospatial dysfunction, but memory impairment is harder to explain.

The determination of whether memory is impaired varies on the basis of clinical evaluation, neuropsychological testing, and which tests are used. For example, one can consider the older and more simplistic rubric that memory impairment is due to an encoding versus retrieval deficit. A deficit in encoding implicates the mesial temporal lobe structures with or without other structures in the limbic system such as the medial thalamus, whereas a retrieval deficit implicates the frontosubcortical neural networks. Most cases of c9FTD/ALS have clinical, neuropsychological, and neuroimaging features implicating the frontosubcortical neural networks, and thus a retrieval deficit would be expected, and in Cilengitide one study in which neuropsychological tests were performed in many c9FTD/ALS subjects, performance on delayed recall measures was usually normal [21].

Yet many cases exhibit selleck catalog poor performance on delayed recall measures as well as on recognition of stimuli [26-28], suggesting an encoding deficit, yet the medial temporal lobes tend to be relatively spared, according to neuroimaging studies conducted thus far [21,26,35]. However, pathologic studies show that hippocampal sclerosis is frequent and associated with those presenting with an amnestic disorder [20].