Primary progressive aphasia and Alzheimer’s dementia: Evolution, pathology and type of language impairment Claudio Luzzatti * , Costanza Papagno, Catia Pegoraro, Daniela Moroni, Sara Spotti Department of Psychology, University of Milano-Bicocca, Piazza dell’Ateneo Nuovo 1, 20126 Milano, Italy Introduction Since Mesulam published his seminal paper in 1982, a large number of primary progressive aphasia (PPA) cases have been described in the neu- ropsychological literature. The objective of the present study is to review the PPA cases documented up to 2005. We have analyzed these cases for type of progression, neuropsychological profile and neuroradiological/ anatomical findings. Materials and methods We reviewed the PPA cases reported in the literature from 1971 to 2005, including a number that were described before Mesulam’s (1982) definition of the syndrome, as well as patients diagnosed as semantic dementia, and cases diagnosed as primary progressive anarthria. The variables included in the study were gender, estimated age at onset, age at first examination (and therefore years of illness prior to diag- nosis), type of language impairment, neuropsychological profile at onset (associated nonverbal deficits) and during the follow-up, neuroradiologi- cal and histopathological data when available. Only those patients who had attended a follow-up evaluation at least 6 months after the first assess- ment were considered in order to evaluate the progression of the disease. The type of language impairment was allocated to one of the standard aphasic syndromes on the basis of the description made by the author/s. The diagnosis of generalized cognitive impairment was based on the asso- ciation of at least three cognitive areas of damage (ideo-motor apraxia, dyscalculia, buccofacial apraxia, verbal memory and/or verbal intelligence impairment were not included, as these symptoms are often associated with verbal damage also in focal left-hemisphere injured patients). Neuroimaging and anatomy findings were grouped into six subsets: two types of diffuse atrophy (bilateral, bilateral with left predominance), three types of left focal atrophy (perisylvian, frontal, temporal and/or parietal) and no atrophy. The histological findings were also grouped into six categories: Alzheimer’s disease, Pick’s disease, mixed, aspecific, spongi- form and multiple system atrophy (MSA). Finally, we analysed the rela- tionships between histological changes and the site of atrophy as well as histological changes and the type of language impairment. Results and discussion The nosography and testing procedures are extremely heterogeneous; in many cases the clinical descriptions are skimpy, with no standardized batteries supporting the assumed absence of associated neuropsychologi- cal deficits; extensive and detailed follow-ups are rare. Altogether, 213 cases were identified in which the initial symptoms of PPA were present; of these, 143 cases had a follow-up and 60 a histological diagnosis. Table 1 summarizes the patients’ distribution by type of language impairment. During the follow-up 48% of the patients showed a clear evolution toward a generalized dementia, whereas in 23% of the cases the follow- up was less than 2 years and, therefore, did not satisfy one of the PPA diagnosis criteria (Kertesz, 1998). doi:10.1016/j.bandl.2007.07.024 * Corresponding author. E-mail address: claudio.luzzatti@unimib.it (C. Luzzatti). Table 1 Type of language impairment in the 143 patients who eventually were given a follow-up examination Type of language impairment 1st eval 1st eval (!PPA) 1st eval (!diffuse) Follow-up Anomic 50 18 32 23 Wernicke 23 15 8 27 Verbal deafness 2 2 — 1 Total fluent 75 35 40 51 Broca 57 31 26 31 Global — — — 22 Mixed transcortical — — — 2 Mutacism — — — 23 Total non-fluent 57 31 26 78 Unclassified 8 5 3 4 Unspecified 3 3 — 10 Grand total 143 74 69 143 1st eval, type of language impairment at first evaluation (at follow-up examination 74 of them maintained the PPA profile and 69 evolved to diffuse language impairment); 1st eval (!PPA), Patients who eventually maintained their PPA profile; 1st eval (!diffuse), Patients who eventually evolved to diffuse impairment; Follow-up. Follow-up, type of language impairment at follow-up evaluation. www.elsevier.com/locate/b&l Brain and Language 103 (2007) 8–249