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ALS ANO FTLO: COGNITIVE CHANGES 
ANO GENET/C MARKERS 
R. M. Lišči6
1
, V. Štukovnik
2
, D. Muck-Šeler3, A. Babi6
3
, G. Nedi6
3
, M. Mustapi6
3
, J. Zidar2
1 
Institute far Medica! Research and Occupational Health, Zagreb, Croatia
2 
Institute of Clinical Neurophysiology, University Medica! Centre Ljubljana, Ljubljana, Slovenia
3 
Division of Molecular Medicine, Ruder Boškovic Institute, Zagreb, Croatia
BACKGROUND 
Amyotrophic laterni sclerosis (ALS) may be accompanied 
by cognitive impairment; when present, it is mainly in the 
form of frontotemporal impairment. Frontotemporal lobar 
degeneration (FfLD) is a focal, non-Alzheimer form of 
dementia, clinically characterized as either behavioral or 
aphasic variants ( I ). The overlap between dementia and ALS 
is demonstrated by the presence of cognitive, behavioural, 
executive dysfunction and change of personality in up to 
50% of ALS patients (2). Behavioural features are mostly 
due to changes in serotoninergic and catecholaminergic 
system (3). 
OBJECTIVE 
To identify genetic correlates of cognitive changes with the 
emphasis on executive function in ALS patients. 
and 6% for CC, CT and TI genotype, respective ly. The f
r
c­
quency of CC, CT, TI genotype for 5-HT2A gene polymor­
phism was 30%, 60% and 10%, respectively. 57% of patients 
showed deficient word generation capability . 21 % of patients 
were impaired on TOL Total move score and 33% of patients 
on TOL Tota! rules violation score. 40% of patients were 
impaired at DRS II Conceptualization subtest and 20% of 
patients on DRS-11 Memory subtest. No significant (p>0.05) 
relationship between genes polymorphism and variables of 
executive functional tests was found (4). 
CONCLUSI ONS 
The preliminary findings reveal a tendency for executive 
deficit in ALS. There is a potential genotype-specific 
influence in ALS for executive functions. Further stud­
ies on a larger sample, however, are needed in order to 
confirm it. 
MATERIALS ANO METHODS 
References: 
In a prospective study, two tests of executive functions (Con­
trolled oral word association - FAS test; Tower of London 
(TOL)), were applied on 16 ALS patients ( 10 male, 60.5 ± 
5.8 years), as defined by EI Escorial Criteria. Ali subjects 
also completed the Dementia Rating Scale II (DRS-11). 1021 
C/T polymorphism of DBH gene, 102 C/T polymorphism of 
5-HT2A receptor gene, val66met polymorphism of COMT
gene and val 158/ 10 8met polymorphism of BDNF gene were
correlated with a cognitive tests.
RESULTS 
ALS patients carrying GG, GA and AA genotype of the 
BDNF gene polymorphism were 73%, 20% and 7%, respec­
tively. The f
r
equency of GG, GA, AA genotype for COMT 
gene 
polymorphism was 33%, 53% and 14%, respectively.
The DBH gene polymorphism distribution was 47%, 47% 
1. McKhann GM, Albert MS, Grossman M, Miller B, Dick­
son D, Trojanowsk i JQ. Work Group on Frontotemporal
Dementia and Pick's Disease. Clinical and pathological
diagnosis of frontotemporal dementia: report of the Work
Group on Frontotemporal Dementia and Pick's Disease.
Arch Neurol 2001; 58 ( 11 ): 1803-9.
2. Lomen-Hoerth C, Anderson T, Miller B. The overlap of
amyotrophic laterni sclerosis and f
r
ontotemporal demen­
tia. Neurology 2002; 59 (7): 1077-9.
3. Huey ED, et al. A systematic review of neurotransmit ­
ter deficits and treatments in frontotemporal dementia.
Neurology 2006; 66: 17-22
4. Liščic RM, et al. Cognitive changes and genetic mark­
ers in amyotrophic laterni sclerosis: Preliminary results
of a prospective study. 6'
h 
International Conference on
Frontotemporal Dementias, Rotterdam 2008 (P-097).
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