Syndromes of nonfluent primary progressive aphasia: a clinical and neurolinguistic analysis.
BACKGROUND
Despite recent work, the nosology of nonfluent primary progressive aphasia (PPA) remains unresolved.


METHODS
We describe a clinical and neurolinguistic cross-sectional analysis of a cohort of 24 patients with nonfluent PPA. Patients were initially classified based on analysis of spontaneous speech into 4 groups: apraxia of speech (AOS)/agrammatism (10 patients); AOS/no agrammatism (4 patients); no AOS/agrammatism (3 patients); no AOS/no agrammatism (7 patients). These groups were further characterized using a detailed neurolinguistic and neuropsychological battery. Parkinsonism was present in 3/10 patients in the AOS/agrammatism group. All patients in the no AOS/agrammatism group had mutations in the progranulin (GRN) gene, while 5/7 cases in the no AOS/no agrammatism group had CSF findings compatible with Alzheimer disease.


RESULTS
The groups without AOS showed more severe neurolinguistic impairments for a given disease stage, and sentence comprehension, speech repetition, and reading were impaired in all groups. Prolonged word-finding pauses and impaired single word comprehension were salient features in the no AOS/agrammatism group. Additional impairments of executive function and praxis were present in both groups with agrammatism, and impaired episodic memory was a feature of the no AOS/no agrammatism group.


CONCLUSIONS
PPA with AOS is aligned with the syndrome previously designated progressive nonfluent aphasia; agrammatism may emerge as the syndrome evolves, or alternatively, the pure AOS group may be pathophysiologically distinct. PPA without AOS resembles the syndrome designated logopenic/phonologic aphasia; however, there is evidence for a distinct subsyndrome of GRN-associated aphasia. The findings provide a rationale for further longitudinal studies with pathologic correlation.
Rohrer
Jonathan D
JD
Dementia Research Centre, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Rossor
Martin N
MN
Warren
Jason D
JD
D000368:Aged; D000369:Aged, 80 and over; D001039:Aphasia, Broca / Q000503:physiopathology; D003072:Cognition Disorders / Q000150:complications; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008037:Linguistics; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D057178:Primary Progressive Nonfluent Aphasia / Q000145:classification / Q000503:physiopathology* / Q000523:psychology*; D012720:Severity of Illness Index; D013060:Speech / Q000502:physiology; D014706:Verbal Learning / Q000502:physiology