Frontotemporal dementia: clinicopathological correlations.
OBJECTIVE
Frontotemporal lobar degeneration (FTLD) is characterized by impairments in social, behavioral, and/or language function, but postmortem studies indicate that multiple neuropathological entities lead to FTLD. This study assessed whether specific clinical features predict the underlying pathology.


METHODS
A clinicopathological correlation was performed on 90 consecutive patients with a pathological diagnosis of frontotemporal dementia and was compared with an additional 24 cases accrued during the same time period with a clinical diagnosis of FTLD, but with pathology not typically associated with frontotemporal dementia.


RESULTS
Postmortem examination showed multiple pathologies including tauopathies (46%), FTLD with ubiquitin-positive inclusions (29%), and Alzheimer's disease (17%). The pathological groups manifested some distinct demographic, clinical, and neuropsychological features, although these attributes showed only a statistical association with the underlying pathology. FTLD with ubiquitin-positive inclusions was more likely to present with both social and language dysfunction, and motor neuron disease was more likely to emerge in these patients. Tauopathies were more commonly associated with an extrapyramidal disorder. Alzheimer's disease was associated with relatively greater deficits in memory and executive function.


CONCLUSIONS
Clinical and neuropsychological features contribute to delineating the spectrum of pathology underlying a patient diagnosed with FTLD, but biomarkers are needed that, together with the clinical phenotype, can predict the underlying neuropathology.
Forman
Mark S
MS
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA.
Farmer
Jennifer
J
Johnson
Julene K
JK
Clark
Christopher M
CM
Arnold
Steven E
SE
Coslett
H Branch
HB
Chatterjee
Anjan
A
Hurtig
Howard I
HI
Karlawish
Jason H
JH
Rosen
Howard J
HJ
Van Deerlin
Vivianna
V
Lee
Virginia M-Y
VM
Miller
Bruce L
BL
Trojanowski
John Q
JQ
Grossman
Murray
M
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D052160:Benzothiazoles; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D003704:Dementia / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D009483:Neuropsychological Tests; D024801:Tauopathies / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D013844:Thiazoles / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D052160:Benzothiazoles; D013844:Thiazoles; D025801:Ubiquitin; C009462:thioflavin T