We defined the neuropsychological and imaging features of the logopenic variant of PPA that in our experience represents 30% of all PPA cases. Our results suggested that the core cognitive deficit in LPA was a phonological loop disorder. Consistently, the imaging investigation showed involvement of GM and WM in the left posterior temporal and inferior parietal regions.
LPA is characterized by a decreased rate of spontaneous language production with frequent halts due to word-finding pauses. Phonemic paraphasias are common, but motor speech and grammar are spared. This pattern of language production is different from the fast output typical of early SemD patients, who usually fill word-finding pauses with circumlocutions and filler words. It is also distinct from the production deficit typical of PNFA, in which articulation deficits and agrammatism predominate.22
LPA patients, therefore, show a pattern of “intermediate” fluency distinct from the fluent SemDs and the nonfluent PNFAs, raising the issue of how to label their language production. Fluency is a composite measure, defined by multiple features of spontaneous language production. The concept was introduced by Goodglass et al.23
to describe language production in vascular aphasia. Within this framework, a patient with would be described as “nonfluent” if he or she exhibited slow, effortful production, with motor speech impairment, defective prosody, and omission of grammatic morphemes. Conversely, fluent aphasic production would be characterized by normal motor speech and production rate, spared grammar, and the presence of phonological and lexical errors. The features of LPA patients’ spontaneous production do not easily fit within this dichotomy, because motor speech is unaffected and grammar is preserved, yet speech production is slowed and halting. LPA patients score as “fluent” on formal aphasia tests, which give more weight to articulation and grammar, but may be labeled as “nonfluent” by the clinician who is impressed by their slow and hesitant production at the bedside (see e-audio for example of spontaneous speech in case 2 two years after initial evaluation reported in ). We suggest that the label “nonfluent” should be reserved for patients who show the motor speech and grammar deficits typical of PNFA. The term logopenic
(from the Greek: “lack of words”) could instead be used to describe the slow language output typical of LPA. Given the phonological nature of this deficit, the term phonological variant
could also be applied.
The disorder of language production in LPA affects sentence repetition severely, yet spares the repetition of single words. A phonological loop disorder had been proposed to underlie this symptom.3
The performance of our patients on the experimental phonological loop battery seems to confirm this hypothesis. LPA patients have markedly reduced digit span but perform normally on single-digit repetition, indicating that their deficit cannot be attributed to defective speech perception. The abolition of the phonological similarity effect suggests that the store component of the phonological loop system is impaired.5
The articulatory rehearsal process was less affected, as evinced by the lack of improvement when the response was made by pointing, and by the partially preserved word length effect, especially in the visual modality.
The phonological loop sustains comprehension by maintaining online incoming verbal information, thus allowing syntactic interpretation of word strings.7
A capacity reduction in the system has been shown to interfere with the ability to process sentences.24
Consistently, LPA patients showed sentence comprehension deficits, regardless of syntactic complexity, whereas single-word comprehension was spared.
LPA most closely resembles vascular conduction aphasia, a syndrome characterized by fluent speech and defective repetition and comprehension of sentences.25
Cases similar to LPA have been reported by Hillis et al.26
as “progressive conduction aphasia” and also by other authors under other PPA-related labels.27,28
Conduction aphasia has been hypothesized to be caused a lesion in the arcuate fasciculus,29
although damage to posterior GM temporoparietal regions has been associated with persistent repetition disorders.30,31
Consistently, our patients with LPA showed GM and WM atrophy within the same region.
Neuroimaging results in LPA showed atrophy or hypoperfusion in left posterior middle and superior temporal and inferior parietal regions, a pattern different from SemD and PNFA. This finding confirmed, at the single-subject level, across languages and across imaging modalities, a previous group study of 10 different LPA patients.3
Both patient series showed similar location of damage, demonstrating that the LPA syndrome is associated with a typical and consistent pattern of anatomic impairment in the left posterior temporoparietal cortices. The previous association of these regions with the phonological store5,31,32
strengthens our findings of a defective functioning of this component of auditory short-term memory in LPA.
Although the term PPA
refers to a clinical syndrome and not to a specific pathologic substrate, it was generally accepted that most cases would show non-Alzheimer, frontotemporal lobar degeneration–type pathology at autopsy. However, recent articles have demonstrated that focal, atypical distribution of Alzheimer disease (AD) pathology is responsible for 20% to 30% of cases with various forms of PPA.2,33–35
Retrospective PET and MRI studies36,37
demonstrated in PPA patients with AD pathology a pattern of temporoparietal involvement similar to LPA. Furthermore, all US patients described in this article had cortical amyloid binding on PET scans using the Pittsburgh compound B tracer.38
Taken together, all these findings suggest that AD could be the most frequent cause of LPA, whereas it may be less frequently responsible for the other PPA syndromes.
We have shown that LPA is a distinctive clinical variant of PPA, associated with a phonological loop disorder and with anatomic damage to the left posterior temporoparietal region. Future studies will establish whether AD is the most common pathology underlying LPA.