. The behavioural/dysexecutive variant of Alzheimer's disease: clinical, neuroimaging and pathological features. Brain. 2015 Sep;138(Pt 9):2732-49. Epub 2015 Jul 2 PubMed.


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  1. In the new framework for the diagnosis of Alzheimer’s disease (AD) that the International Working Group has proposed since 2007, we introduced the concept that AD is a “clinical-biological entity”. This means that AD should be identified in patients first on the basis of a specific clinical phenotype. The most frequent phenotype is the “amnestic syndrome of the hippocampal type” (that we have described and defined as “typical AD”).

    Other additional clinical presentations can be encountered: they were described in 2010 as atypical forms of AD, which include the posterior variant of AD, the logopenic variant of AD and the frontal variant of AD (Dubois et al., 2010). These clinical phenotypes are related to AD on the positivity of biomarker of AD pathology (specific changes in the CSF or positive amyloid PET). In our mind, the role of biomarkers is mainly to confirm the clinical evidence for AD.

    Therefore, it is mostly important to better describe the clinical phenotypes of AD. This is the aim of this paper and this is, no doubt, a significant contribution to the field.

    View all comments by Bruno Dubois
  2. This timely paper illustrates two important principles relevant to dementia research in general. The first is that the same neuropathologic entity can give rise to multiple clinical syndromes, some more typical than others. The second is that Alzheimer’s disease has subtypes. They include not only the typical amnestic variant but also variants that predominantly undermine language (as in the primary progressive aphasia [PPA] syndrome), visuospatial function (as in the posterior cortical atrophy syndrome), and, as shown in this paper, executive/behavioral domains. These principles were illustrated by PPA, which can be caused by at least eight different pathological entities, including Alzheimer’s. Furthermore, the Alzheimer pathology that causes PPA displays an atypical asymmetry of neurofibrillary tangles, is not linked to ApoE4 as a risk factor, and does not display the relatively high frequency of TDP-43 precipitates detected in typical forms of AD (Bigio et al., 2010Gefen et al., 2012; Mesulam et al., 2014). The careful clinicopathologic analyses in the report by Ossenkoppele and colleagues shed further light on the factors that underlie the intriguing syndromic diversity of neurodegenerative diseases.


    . TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease. Acta Neuropathol. 2010 Jul;120(1):43-54. PubMed.

    . Clinically concordant variations of Alzheimer pathology in aphasic versus amnestic dementia. Brain. 2012 May;135(Pt 5):1554-65. PubMed.

    . Asymmetry and heterogeneity of Alzheimer's and frontotemporal pathology in primary progressive aphasia. Brain. 2014 Apr;137(Pt 4):1176-92. Epub 2014 Feb 25 PubMed.

    View all comments by Marsel Mesulam

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This paper appears in the following:


  1. ‘Frontal AD’ a Misnomer? Behavioral Variant Has Minimal Frontal Atrophy