Longitudinal decline in autopsy-defined frontotemporal lobar degeneration.
BACKGROUND
The natural history of patients with pathologically proven frontotemporal lobar degeneration (FTLD) is important from clinical and biologic perspectives, but is not well documented quantitatively.


METHODS
We examine longitudinal decline in cognitive functioning in an autopsy-proven cohort of patients with the clinical diagnosis of a FTLD spectrum disorder or FTLD pathology using a panel of neuropsychological measures. Patients are categorized according to findings at autopsy into tau-positive FTLD, tau-negative FTLD, and frontal variant-Alzheimer disease (fvAD) subgroups.


RESULTS
Patients decline significantly over time on all neuropsychological measures. Moreover, several measures differentiate between histopathologically distinct subgroups throughout the course of the disease process. This includes a significant double dissociation involving relative difficulty on a visual constructional measure in tau-positive patients compared to relatively impaired visual confrontation naming in tau-negative patients. Longitudinal measures of FAS naming fluency and animal naming fluency also distinguish tau-positive patients and tau-negative patients with FTLD from patients with fvAD. Other measures show significant decline but do not distinguish between histopathologic groups longitudinally.


CONCLUSIONS
Our findings suggest different longitudinal patterns of cognitive decline in pathologically defined subgroups of patients. Measures consistently distinguishing between patient subgroups can be used to bolster diagnostic accuracy throughout the course of these diseases, while measures demonstrating undifferentiated longitudinal decline may serve as useful endpoints in treatment trials.
Grossman
M
M
Department of Neurology, University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104-4283, USA. mgrossma@mail.med.upenn.edu
Xie
S X
SX
Libon
D J
DJ
Wang
X
X
Massimo
L
L
Moore
P
P
Vesely
L
L
Berkowitz
R
R
Chatterjee
A
A
Coslett
H B
HB
Hurtig
H I
HI
Forman
M S
MS
Lee
V M-Y
VM
Trojanowski
J Q
JQ
D000368:Aged; D001344:Autopsy; D015331:Cohort Studies; D003704:Dementia / Q000209:etiology / Q000473:pathology* / Q000523:psychology*; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009483:Neuropsychological Tests