Associated and predictive factors of depressive sy

Authors: Kangdi Zhu Jacobus J van Hilten Johan Marinus

Publish Date: 2016/04/28

Volume: 263, Issue: 6, Pages: 1215-1225

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Abstract

Depression is one of the most common nonmotor symptoms in Parkinson’s disease PD A thorough understanding of factors associated with depressive symptomatology may facilitate early detection and guide future intervention strategies The objective of the study was to determine associated and predictive factors of depression in patients with PD Analyses were performed in data of the SCOPAPROPARK cohort a 5year hospitalbased longitudinal cohort of over 400 PD patients who have been examined annually Linear mixed models using data of all patients were used to identify factors associated with longitudinal changes in Beck Depression Inventory BDI scores A survival analysis using data of patients without depression at baseline was performed to identify risk factors for future depression ie BDI ≥ 15 The proportion of patients with depression was approximately 20  and remained stable during followup with approximately half of cases showing a persistent course Female gender more severe disability more severe motor fluctuations autonomic and cognitive dysfunction poorer nighttime sleep and daytime sleepiness were independently associated with higher BDI scores over time Higher baseline BDI score daytime sleepiness and a higher levodopa dosage were risk factors for future depression Depression is common in PD where it may follow a persistent or nonpersistent course Apart from motor fluctuations and levodopa dose depressive symptoms in PD are mainly associated with factors of nondopaminergic origin This suggests that depression in PD is an inherent consequence of the progressive pathobiology of the disease which may render its treatment with currently available treatment options difficultWith a prevalence of about 40  depression is one of the most common nonmotor symptoms of Parkinson’s disease PD 1 It contributes significantly to the disease burden 2 and several studies identified depression as the main determinant of poor quality of life in PD patients 3 Symptoms that contribute to the clinical semiology of depression show an overlap with those primarily related to PD or those related to the side effects associated with the use of medication 4 This renders the identification of depression in PD difficult and it is assumed that this condition frequently remains unrecognized 5 Increased knowledge of associated and risk factors of depression in PD may therefore facilitate its early detection provide insight into the nature of this condition and guide future intervention strategies 5 6In earlier studies in PD consistent relations have been found between depression and age anxiety insomnia and dementia However contradictory findings have been reported for the relation between depression and gender disease stage levodopa treatment and motor subtype postural instability/gait difficulty PIGD 7 8 9 10 11 12 13 14 15 16 17 18 19 20These inconsistencies are likely explained by differences between studies concerning sample size population characteristics and study design Most previous studies on depression in PD had a crosssectional design and to our knowledge only three longitudinal studies have been performed to date 7 10 11 One longitudinal hospitalbased study n = 685 showed that longer disease duration greater disability and a positive family history of motor neuron disease were risk factors associated with the development of depression 10 Another hospitalbased study n = 184 found that the severity of depression in PD varied over time with groups showing a remittent 35  stable 34  or progressive 31  form 7 The largest longitudinal populationbased case–control study performed by Becker et al 3637 PD patients and controls showed an almost twofold increased risk to develop depression in the patients with PD Female gender and longterm levodopa usage emerged as the most important risk factors of depression 11 Unfortunately in all longitudinal studies the number of baseline features used in the analysis was limited This specifically pertains to nondopaminergic features which are less sensitive to dopaminergic medication and may provide a more complete and accurate evaluation of disease severity and progression in PD 21The PROPARK cohort study includes over 400 PD patients who have been examined annually and followed for 5 years ie six assessments on a broad range of motor and nonmotor features 22 This cohort is therefore very wellsuited to investigate which factors are associated with 1 the presence of depression in PD 2 the longitudinal changes in severity of depressive symptoms and 3 the development of future depression in PDPatients were recruited from neurology clinics of university and regional hospitals in the western part of The Netherlands and all fulfilled the United Kingdom Parkinson’s disease Society Brain Bank criteria for idiopathic PD 23 The majority of patients were evaluated at the Leiden University Medical Center but more severely affected patients were offered the possibility to be examined at their homes to prevent selective dropout In view of the fact that we aimed to obtain information on the full spectrum of the disease a recruitment strategy based on age at onset  or ≥50 years and disease duration  or ≥10 years was applied We intended to recruit at least 100 patients in each of the four strata 22 The medical ethical committee of the Leiden University Medical Center approved the PROPARK study and written informed consent was obtained from all patients 22At baseline 2003–2005 and the five subsequent annual visits all patients received standardized assessments The assessments included an evaluation of demographic and clinical characteristics family history of PD and registration of antiparkinsonian medication A levodopa dose equivalent LDE of daily levodopa and dopamine agonists dose was calculated for each patient at baseline The total LDE is the sum of levodopa dosage equivalent LDEDopa and the dopamine agonist dosage equivalent LDEDA 24 Diagnosis and Hoehn Yahr HY stages of the patients were ascertained at every assessment 25 The following instruments were administered by qualified examiners the SPES/SCOPA 26 including sections on motor examination activities of daily living and motor complications the SCOPACOG cognitive function 27 and the SCOPAPC psychotic symptoms items 1–5 28 Over the years there were in total five examiners who all regularly attended retraining and recalibration sessions to prevent interrater variability All patients who used dopaminergic medication were assessed during “on’’ Patients completed the following instruments themselves the SCOPAAUT three autonomic domains gastrointestinal urinary tract and cardiovascular 29 the SCOPASLEEP with sections on nighttime sleep problems NS and daytime sleepiness DS 30 and the Beck Depression Inventory BDI 31

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