Quantitative template for subtyping primary progressive aphasia.
BACKGROUND
The syndrome of primary progressive aphasia (PPA) is diagnosed when a gradual failure of word usage or comprehension emerges as the principal feature of a neurodegenerative disease.


OBJECTIVE
To provide a quantitative algorithm for classifying PPA into agrammatic (PPA-G), semantic (PPA-S), and logopenic (PPA-L) variants, each of which is known to have a different probability of association with Alzheimer disease vs frontotemporal lobar degeneration.


METHODS
Prospective study.


METHODS
University medical center.


METHODS
Sixteen consecutively enrolled patients with PPA who underwent neuropsychological testing and magnetic resonance imaging recruited nationally in the United States as part of a longitudinal study.


RESULTS
A 2-dimensional template that reflects performance on tests of syntax (Northwestern Anagram Test) and lexical semantics (Peabody Picture Vocabulary Test-Fourth Edition) classified all 16 patients in concordance with a clinical diagnosis that had been made before the administration of quantitative tests. All 3 PPA subtypes had distinctly asymmetrical atrophy of the left perisylvian language network. Each subtype also had distinctive peak atrophy sites: PPA-G in the inferior frontal gyrus (Broca area), PPA-S in the anterior temporal lobe, and PPA-L in Brodmann area 37.


CONCLUSIONS
Once an accurate root diagnosis of PPA is made, subtyping can be quantitatively guided using a 2-dimensional template based on orthogonal tasks of grammatical competence and word comprehension. Although the choice of tasks and the precise cutoff levels may need to be adjusted to fit linguistic and educational backgrounds, these 16 patients demonstrate the feasibility of using a simple algorithm for clinicoanatomical classification in PPA. Prospective studies will show whether this subtyping can improve clinical prediction of the underlying neuropathologic condition.
Mesulam
Marsel
M
Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, Chicago, Illinois 60611, USA. mmesulam@northwestern.edu
Wieneke
Christina
C
Rogalski
Emily
E
Cobia
Derin
D
Thompson
Cynthia
C
Weintraub
Sandra
S
D000368:Aged; D000544:Alzheimer Disease / Q000145:classification / Q000175:diagnosis; D018888:Aphasia, Primary Progressive / Q000145:classification* / Q000175:diagnosis*; D001931:Brain Mapping / Q000379:methods*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000145:classification / Q000175:diagnosis; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies