Abstract
Study A. Aim: To investigate whether there is an association of the postural instability and gait difficulty (PIGD) motor subtype with cognitive dysfunction in non-demented Parkinson’s disease (PD) patients. Methods: We administered a battery of selected neuropsychological tests to assess attention, psychomotor speed, executive functions (set shifting ability and inhibitory control), visuospatial perception and visual constructive ability to two groups of non-demented patients with mild to moderate disease classified either as PIGD or as non-PIGD subtype and to a group of healthy controls. Groups were matched on potential confounders of neuropsychological performance. Results: No significant differences were revealed between the two groups of patients in the performance of any of the administered neuropsychological tests. However, relative to controls there was a tendency towards a differential pattern of cognitive dysfunction. The PIGD group had slower performance in a test of psychom ...
Study A. Aim: To investigate whether there is an association of the postural instability and gait difficulty (PIGD) motor subtype with cognitive dysfunction in non-demented Parkinson’s disease (PD) patients. Methods: We administered a battery of selected neuropsychological tests to assess attention, psychomotor speed, executive functions (set shifting ability and inhibitory control), visuospatial perception and visual constructive ability to two groups of non-demented patients with mild to moderate disease classified either as PIGD or as non-PIGD subtype and to a group of healthy controls. Groups were matched on potential confounders of neuropsychological performance. Results: No significant differences were revealed between the two groups of patients in the performance of any of the administered neuropsychological tests. However, relative to controls there was a tendency towards a differential pattern of cognitive dysfunction. The PIGD group had slower performance in a test of psychomotor speed and cognitive flexibility, whilst the non-PIGD group performed worse in measures of verbal learning and visuo-spatial perception. Conclusions: The PIGD subtype was not associated with more severe cognitive deficits and may to a certain extent share common mechanisms of cognitive dysfunction with non-PIGD subtypes. Study B. Aim: to investigate whether there is an association between PD and a variation in the CHRNA4 gene coding for the α4 subunit, the primary subunit of the α4β2 brain nicotinic acetylcholine receptors. Methods: Patients (N=100) and controls (N=105), matched on the basis of sex, age and ethnicity, were genotyped for a single nucleotide polymorphism at cDNA position 1860 lying within the 5th exon of the CHRNA4 gene. DNA was extracted from peripheral blood samples and genotyping was done by PCR-based restriction fragment length polymorphism analysis. A subset of 42 patients also received detailed clinical and cognitive assessments. Comparisons of allele and genotype frequencies between groups were performed using the χ² test, and the Fisher exact test if one cell had n<5. The relative risk for genotypes and alleles was estimated through calculation of odds ratios (ORs) with 95% confidence intervals (CIs). Logistic regression analysis was used if adjustment for age or sex was necessary. Results: The genotype frequencies in the patients group (TT 34%; CT 58%; CC 8%) vs. the genotype frequencies in the control group (TT 28.6 %; CT 47.6%; CC 23.8 %) demonstrated a statistically significant difference (χ2 = 9.48, df = 2, p = 0.009). CC homozygosity was associated with a lower risk of PD (CC vs T carriers: OR = 0.28; 95% CI = 0.12–0.65; p = 0.002). Also, the allelic distribution was significantly different between patients and controls. There was a significantly lower frequency of the C allele among the patients with PD (37%) as compared with the controls (47.6%) (χ2 = 4.73; df = 1; OR = 0.65; 95% CI = 0.44–0.96; p = 0.03). Stratified analysis showed that the difference in the genotypic distribution between cases and controls was significant among females but did not reach significance among males. The frequency of CC homozygotes was also significantly lower in the group of patients with late onset PD than in the controls, but it was not significantly different between the early onset group of patients and the controls. CC homozygotes also tended to have better performance than T carriers on measures of attention and psychomotor speed (Trail Making Test part A and Symbol Digit Modalities Test). Conclusions: The presence of the C allele at SNP rs1044396 of the CHRNA4 gene is associated with a decreased risk for PD by 35%. Moreover, the CC genotype lowers the risk for PD by ~ 3.5 fold. Variation in the CHRNA4 gene may particularly influence susceptibility for late onset PD and further be associated with measurable effects on overt cognitive performance of yet not-demented PD patients, specifically the part loading on attentional capacities.
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