Clinical marker for Alzheimer disease pathology in logopenic primary progressive aphasia.

OBJECTIVE: To determine whether logopenic features of phonologic loop dysfunction reflect Alzheimer disease (AD) neuropathology in primary progressive aphasia (PPA). METHODS: We performed a retrospective case-control study of 34 patients with PPA with available autopsy tissue. We compared baseline and longitudinal clinical features in patients with primary AD neuropathology to those with primary non-AD pathologies. We analyzed regional neuroanatomic disease burden in pathology-defined groups using postmortem neuropathologic data. RESULTS: A total of 19/34 patients had primary AD pathology and 15/34 had non-AD pathology (13 frontotemporal lobar degeneration, 2 Lewy body disease). A total of 16/19 (84%) patients with AD had a logopenic spectrum phenotype; 5 met published criteria for the logopenic variant (lvPPA), 8 had additional grammatical or semantic deficits (lvPPA+), and 3 had relatively preserved sentence repetition (lvPPA-). Sentence repetition was impaired in 68% of patients with PPA with AD pathology; forward digit span (DF) was impaired in 90%, substantially higher than in non-AD PPA (33%, p < 0.01). Lexical retrieval difficulty was common in all patients with PPA and did not discriminate between groups. Compared to non-AD, PPA with AD pathology had elevated microscopic neurodegenerative pathology in the superior/midtemporal gyrus, angular gyrus, and midfrontal cortex (p < 0.01). Low DF scores correlated with high microscopic pathologic burden in superior/midtemporal and angular gyri (p ≤ 0.03). CONCLUSIONS: Phonologic loop dysfunction is a central feature of AD-associated PPA and specifically correlates with temporoparietal neurodegeneration. Quantitative measures of phonologic loop function, combined with modified clinical lvPPA criteria, may help discriminate AD-associated PPA.

Longitudinal assessment of language and memory impairments in pathologically confirmed cortico-basal ganglionic degeneration.

We report a longitudinal case study (patient EP) of histologically confirmed cortico-basal ganglionic degeneration (CBD) who presented with non-fluent progressive aphasia (NFPA). While NFPA has been documented in clinical descriptions of other reports of CBD, details are often limited and the majority of studies are cross-sectional in nature. The present study conducted detailed longitudinal assessment with EP over a period of two years that revealed substantial impairments of episodic memory, semantic memory, naming and particular aspects of reading and spelling. Our investigations identify key features of EP's pattern of impairment that warrant further examination with other cases of CBD. In particular, testing of EP's nonword reading and spelling found that both were impaired and declined over time. In addition, verbal recognition deteriorated faster than non-verbal recognition through the course of the disease. Our review of the literature suggests that poor nonword reading and spelling may be consistent features of CBD, but more studies are needed to confirm this suggestion, and to determine whether they warrant inclusion in profiling CBD.