Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by progressive degeneration of spinal and bulbar motor neurons. However up to 50% ALS patients may also have cognitive dysfunction which has not been fully examined.
35 ALS patients [23 patients presenting with limb-type ALS (ALS-limb) and 12 patients presenting with primary bulbar palsy (PBP)-type ALS (ALS-PBP)] and 5 Spinal and Bulbar Muscular Atrophy (SBMA) patients have participated. To assess cognitive function mini-mental state examination (MMSE), Hasegawa dementia scale—revised (HDS-R), and frontal assessment battery (FAB) were performed. Additionally the time to complete card flipping with a computerized touch panel-type screening test was also examined. To investigate regional cerebral blood flow (rCBF), single-photon emission computed tomography (SPECT) using a 99mTc labeled ethyl cysteinate dimer (99mTc-ECD) were performed. Statistical image analysis was performed using the easy Z-score imaging system (eZIS).
HDS-R and FAB scores were significantly lower in the ALS-PBP group than in age- and gender-matched control subjects or ALS-limb groups (p<0.01). The time to complete card flipping was significantly longer in the ALS-PBP group than in the control and ALS-limb groups (p<0.01). Although MMSE, HDS-R and FAB scores and the time to complete card flipping had no correlation with ALS functional rating scale—revised (ALSFRS-R) or Norris-limb scale scores, FAB score (r=0.63, p <0.01) and the time to complete card flipping (r=−0.66, p<0.01) were strongly correlated with Norris-bulbar score. The eZIS showed that rCBF of the frontal lobe was more severely declined in ALS-PBP patients than in ALS-limb patients (p<0.05).
These results suggest a selective decline of frontal cerebral functions in the ALS-PBP group in relation to their bulbar symptoms and rCBF decline.
Abbreviations:AD (Alzheimer's disease), ALS (amyotrophic lateral sclerosis), ALSFRS-R (ALS functional rating scale—revised), AR (androgen receptor), SBMA (Spinal and bulbar muscular atrophy), CDR (Clinical Dementia Rating), eZIS (easy Z-score imaging system), FAB (frontal assessment battery), FTLD (frontotemporal lobar degeneration), HDS-R (Hasegawa dementia scale—revised), MMSE (mini-mental state examination), MND (motor neuron disease), rCBF (regional cerebral blood flow), ROI (region of interest), SOD1 (superoxide dismutase 1), SPM (statistical parametric mapping), SPECT (single-photon emission computed tomography), 99mTc-ECD (99mTc labeled ethyl cysteinate dimer), TDP-43 (transactivation responsive region (TAR)-DNA-binding protein of 43kDa)
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Published online: May 21, 2012
Accepted: April 30, 2012
Received in revised form: April 3, 2012
Received: January 10, 2012
© 2012 Elsevier B.V. Published by Elsevier Inc. All rights reserved.