Education Effect on Depression and Quality of Life in Nondemented Parkinson’s Disease Patients

Candidates were consecutive idiopathic Parkinson’s disease patients diagnosed according to standard criteria. 16 Inclusion criteria were informed consent and a lack of dementia. Exclusion criteria were somatic diseases with a potential relevant effect on mood, cognition, or quality of life (advanced cerebrovascular diseases or sequelae; chronic pain syndromes; chronic inflammatory/infectious diseases; advanced diabetes mellitus; malignancy; renal, hepatic, or heart failure; severe anemia or any other severely debilitating or life-threatening disease/state); neurodegenerative diseases other than Parkinson’s disease; history of or an ongoing psychotic disorder or presence of hallucinations, delusions or a delirium; history of or an ongoing antipsychotic treatment; and use of antidepressants/anxiolytics within 6 months before the study (at least 3 weeks of continuous treatment). Patients were considered nonpsychotic based on psychiatric evaluation (DSM-IV) and considered nondemented based on both psychiatric evaluation (DSM-IV) and a Mini Mental State Examination (MMSE) score equal to or higher than the median value established in a reference population-based group of the corresponding age and education. 17

Patients were evaluated during the “on” (motor symptom-free) state. The Beck Depression Inventory (BDI) (validated Croatian version) was used to measure the level of depression (11 cognitive-affective items as specified by Visser et al.: 18 mood, pessimism, sense of failure, lack of satisfaction, guilty feeling, sense of punishment, self-hate, self-accusations, suicidal ideas, irritability, and social withdrawal; higher score indicates more severe depression). The Croatian version of a 39-item self-reporting quality of life questionnaire validated for use in Parkinson’s disease (Parkinson’s Disease Questionnaire, PDQ-39) 19 was used to assess health-related quality of life (higher score indicates poorer health-related quality of life). Neuropsychological evaluation included standardized tests for cognitive domains typically affected in Parkinson’s disease (memory/attention, visuospatial and executive functions): 8 Stroop interference test (attention, mental speed, mental control); 20 Symbol Digit Modalities (visuoverbal substitution speed); 21 Rey Auditory Verbal Learning test (verbal memory) 22 with five learning trials of a 15-word list and the immediate-recall task; Rey-Osterreith Complex Figure test (visuomotor organization and memory) 23 with the two testing conditions freehand copy of the figure and reproduction of the figure after 30 minutes (recall); and Trail Making tests A and B (visual, conceptual, and visuomotor tracking). 24 Higher scores indicated better performance in all tests except Trail Making tests A and B. Tests were implemented by an investigator unaware of the patients’ educational level and BDI scores.

Parkinsonism was evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III and modified Hoehn and Yahr Parkinson’s disease staging scale. 25 UPDRS Part II evaluates activities of daily living by scoring 13 items from 0 to 4 points (0=normal, 4=most impairment for each item); the scale is 0 to 3 for the salivation item. UPDRS Part III is a detailed motor exam that evaluates 27 items on a five-point scale (0=normal, 4=most impairment). UPDRS Part I was not considered since its items were either assessed by more detailed testing or were part of the exclusion criteria (thought disorders such as hallucinations, delusions, or psychosis). Modified Hoehn and Yahr Parkinson’s disease grading has 8 levels based on unilateral or bilateral motor symptoms and ability to walk/stand (0=no disease, 1, 1.5, 2, 2.5, 3, 4, 5=wheelchair-bound or bedridden unless assisted).

Data on Parkinson’s disease history, education, and other sociodemographic characteristics were collected from a structured interview. We calculated the average daily L -dopa dose over the 4 weeks preceding the evaluation.

Unadjusted group comparisons were based on appropriate univariate tests for trends or differences in proportions, medians, or means. A number of sociodemographic and Parkinson’s disease-related characteristics were considered as covariates in the adjusted comparisons (analysis of covariance). Their number was partly reduced by the means of principal components analysis (varimax rotation, Kaiser normalization). To check whether the patients could be separated based on depression level and health-related quality of life, cluster analysis was performed that used least p th powers clustering criterion (p=1) to reduce the effect of outliers on cluster centers. To validate the results of the main analysis, cluster allocation prevalence was analyzed using modified Poisson regression with robust error variance. We used SAS for Windows 9.1 software (SAS Inc., Cary, NC).

A total of 114 patients (24 lower, 53 intermediate, 37 higher education level) from a broad metropolitan area were enrolled. Groups were comparable regarding MMSE score and sociodemographic characteristics ( Table 1 ). Motor symptoms were more severe in the lower education group than in the remaining two groups (UPDRS Part III), whereas other Parkinson’s disease-related characteristics appeared comparable: duration, early onset, activities of daily living (UPDRS Part II) and Hoehn and Yahr Parkinson’s disease score ( Table 1 ) (distribution across Hoehn and Yahr stages χ ² =9.85, df=10, p=0.454). Cognitive tests performance and health-related quality of life (PDQ-39 score) were better, while depressive difficulties (cognitive-affective BDI items score) were less severe, with increasing educational level ( Table 1 ). Use of L -dopa, dopaminergic agonists (ropinirole or pramipexole) or monoamine oxidase B inhibitors (selegiline) was comparable across the groups ( Table 2 ).

In the first run, age had a communality less than 0.5 and was thereafter considered as a separate variable. The remaining variables were conceptually close and correlated: UPDRS Part II, Part III, and Hoehn and Yahr score (pairwise Kendall’s nonparametric correlation coefficients τ-b between 0.340 and 0.435, p<0.001 in all cases); Parkinson’s disease duration, history of use and L -dopa dose (pairwise correlations τ-b between 0.532 and 0.733, p<0.001 in all cases); and cognitive tests (pairwise correlations τ-b between 0.282 and 0.532, p<0.001 in all cases). Cognitive tests loaded onto the first component named “cognition” (cognitive performance, higher is better); Parkinson’s disease duration, history of use, and L -dopa dose loaded onto the second component named “duration-dopa” (higher is worse); UPDRS Part II, Part III, and Hoehn and Yahr loaded onto the third component named “Parkinson’s disease severity” (higher is worse). All communalities were ≥0.55, loadings were between 0.705 and 0.912, total variance explained was 65.9%, there were no outliers, and each variable loaded onto a single component. Similar communalities, eigenvalues, and loadings were obtained in randomly selected data (random number seed based on the analysis date) confirming validity of the model.

In our analysis of covariance (ANCOVA) with adjustment for “cognition,” use of dopaminergic agonists or selegiline (by default), and covariates with p<0.250 ( Table 3 ), educational level groups were significantly different (F=8.41, df=2, p<0.001) with respect to cognitive-affective BDI items score, and depression level progressively decreased from lower to higher education level group ( Table 3 ). More severe depression appeared associated with worse “Parkinson’s disease severity” and “duration-dopa” ( Table 3 ).

In ANCOVA, with adjustment for cognitive-affective BDI score, age (F=41.8, df=1, p<0.001) (by default) and covariates with p<0.250 (“Parkinson’s disease severity,” using dopaminergic agonists or selegiline), educational level groups were significantly different regarding “cognition” (F=12.7, df=2, p<0.001), and cognitive performance progressively increased from lower to higher education level group (not shown).

Health-related quality of life (PDQ-39, higher score=poorer quality of life) was compared among the groups in ANCOVA with different adjustment for “cognition” and depression level ( Table 4 ). First, “cognition” and depression level were disregarded; “Parkinson’s disease severity,” “duration-dopa,” and using agonists/selegiline were included by default, while other covariates were included if p<0.250. Educational level groups significantly differed (F=6.45, df=2, p=0.002), and health-related quality of life was progressively better from lower to higher education group ( Table 4 ). Then, depression level was disregarded, whereas “cognition” was added by default (other covariates if p<0.250). Higher education patients had somewhat better health-related quality of life but differences were no longer significant (F=2.73, df=2, p=0.069). Better “cognition” was associated with better health-related quality of life (F=9.98, df=1, p=0.002) ( Table 4 ). Next, “cognition” was disregarded, whereas depression level was included by default (other covariates if p<0.250). Again, higher education level patients had somewhat better health-related quality of life, but differences were not significant (F=1.15, df=2, p=0.321). Higher level of depression was associated with poorer health-related quality of life (F=21.4, df=1, p<0.001) ( Table 4 ). Finally, both “cognition” and depression level were added as default covariates (other covariates if p<0.250) ( Table 5 ). Differences among educational level groups were not significant (F=0.93, df=2, p=0.396), whereas better health-related quality of life was associated with better “cognition” (F=14.7, df=1, p<0.001) and lower depression level (F=29.4, df=1, p<0.001) ( Table 5 ). The effect of “cognition” was conditional on age (F = 10.2, df=1, p=0.002), and the effects of “cognition” and depression were conditional on each other (F = 6.56, df=1, p = 0.012) ( Table 5 ). The score on the PDQ-39 decreased with better “cognition” only in younger patients (below the mean age); PDQ-39 decreased with better “cognition” only in patients with lower BDI scores (below the mean value), whereas PDQ-39 increased with higher BDI scores only in patients with better “cognition” (above the mean value). Poorer health-related quality of life appeared associated with female sex, worse “Parkinson’s disease severity,” and “duration-dopa” ( Table 5 ).

Cognitive-affective BDI items score and PDQ-39 score were correlated ( τ-b =0.650, p<0.001). Patients formed two clusters: A, with a low depression level and better health-related quality of life (n=51, median BDI=2, quartiles 0–4; median PDQ-39=33, quartiles 20–50), and B, with a higher depression level and poorer health-related quality of life (n=63, median BDI=9, quartiles 5–17; median PDQ-39=86, quartiles 74–100). Prevalence of patients allocated to cluster B was 79.2% for lower, 58.5% for intermediate, and 35.1% for higher education level groups. In a regression analysis, risk of allocation to cluster B was greater for lower and intermediate than higher education level patients ( Table 6 ).