title: Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia.
abstract: OBJECTIVE
  Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) are hypothesized to cause clinically distinct forms of primary progressive aphasia (PPA) that predominantly affect expressive speech. AD is thought to cause logopenic progressive aphasia (LPA), and FTLD may cause progressive nonfluent aphasia (PNFA). We sought to determine the value of clinical characterization, neuropsychological analysis, and MRI atrophy in predicting pathology of LPA and PNFA.
  
  
  METHODS
  Patients with LPA (n = 19) and patients with PNFA (n = 19) were evaluated with neuropsychological assessments, structural MRI, CSF analysis, and neuropathologic examination.
  
  
  RESULTS
  Twelve of 19 patients with LPA (63%) and 6 of 19 patients with PNFA (32%) had neuropathologic findings or CSF biomarkers consistent with AD. Neuropsychological testing showed that naming was more impaired in patients with AD, and letter-guided fluency was more affected in patients with a non-AD disorder. Voxel-based morphometry analysis revealed that in patients with AD, patients with LPA and PNFA had significant posterior-superior temporal atrophy; in patients with non-AD, patients with LPA had peri-Sylvian atrophy and patients with PNFA had dorsolateral prefrontal and insular atrophy. Receiver operator characteristic curve analysis showed that combining neuropsychological testing with MRI atrophy pattern had 90% specificity for pathology or CSF biomarkers consistent with AD, and combining clinical features with neuropsychological analysis had 100% sensitivity for pathology or CSF biomarkers consistent with AD.
  
  
  CONCLUSIONS
  Neither PPA phenotyping nor imaging alone is a reliable predictor of pathology. Multimodal predictors, such as combining neuropsychological testing with MRI analysis, can improve noninvasive prediction of underlying pathology in nonfluent forms of PPA.
authors: Department of Neurology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19106, USA.
authors: W T
authors: WT
authors: Hu
authors: C
authors: C
authors: McMillan
authors: D
authors: D
authors: Libon
authors: S
authors: S
authors: Leight
authors: M
authors: M
authors: Forman
authors: V M-Y
authors: VM
authors: Lee
authors: J Q
authors: JQ
authors: Trojanowski
authors: M
authors: M
authors: Grossman
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000150:complications*; D001284:Atrophy / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000134:cerebrospinal fluid / Q000150:complications; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D057178:Primary Progressive Nonfluent Aphasia / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000209:etiology*; D012372:ROC Curve