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Table 1 Composite scores and proportions with positive and clinically Table 2 Demographic and clinical features of early PD patients in the
significant item scores on the NPI in early PD and control subjects two neuropsychiatric clusters and in those with no or mild
% with a neuropsychiatric symptoms
positive % with a clinically No/mild Mood Apathy
Mean score score significant score* symptoms cluster cluster Statistic* p Value
NC PD NC PD NC PD Age 67.5 (9.0) 69.0 (9.1) 75.1 (8.7) 1.5 0.24
Delusions 0.0 0.06 0 1.1 0 0.6 Men/women (n) 90/58 7/3 3/1 1.1 0.3
Hallucinations 0.01 0.04 0.6 1.2 0 0.6 Education (years) 11.0 (3.3) 10.0 (4.0) 8.4 (1.8) 1.6 0.21
Agitation 0.02 0.15 1.2 5.7 0 1.1 MMSE score 27.9 (2.4) 28.0 (2.1) 24.5 (1.7) 4.0 0.02
Depression 0.11 1.06 7.8 34.3 0.6 10.3 UPDRS motor score 22.8 (11.2) 31.7 (9.7) 35.3 (11.5) 5.1 0.007
Anxiety 0.07 0.59 2.4 16.4 0.6 6.9 Values are mean (SD) unless otherwise indicated.
Euphoria 0 0 0 0 0 0 *One way ANOVA.
Apathy 0.03 1.06 1.2 27.4 0 11.4 MMSE, Mini-Mental State Examination Scale; PD, Parkinson’s disease; UPDRS motor,
Unified Parkinson’s Disease Rating Scale, motor subscale.
Disinhibition 0 0.08 0 4.0 0 0.6
Irritability 0.14 0.22 5.4 8.6 1.2 1.7
Motor behaviour 0.02 0.14 0.6 2.3 0.6 1.7 Antidepressant drugs were used by 23 (13.1%) patients, one
Sleep disturbance 0.2 0.69 9.1 17.8 1.8 7.5 (0.6%) used an antipsychotic, and a benzodiazepine was used by
Appetite 0.09 0.70 1.8 14.9 0.6 8.0 21 (12%) patients (regularly by 19, intermittently by two). The
disturbance proportions taking antidepressants (35.6% vs 5.8%; x2 = 26.1,
*Clinically significant neuropsychiatric symptoms, defined as a NPI score >4. p,0.001) and benzodiazepines (26.7% vs 5.5%; x2 = 15.3,
NC, normal controls; NPI, Neuropsychiatric Inventory; PD, Parkinson’s disease. p,0.001) were higher among those with at least one significant
neuropsychiatric symptom compared with those without
investigated the plot for an ‘‘elbow’’. A p value ,0.05 was significant neuropsychiatric symptoms.
considered statistically significant. Cluster analysis was performed to explore whether groups
with specific neuropsychiatric syndromes could be identified.
RESULTS Five clusters were identified, based on the finding of a very clear
Among the 201 eligible PD patients and 175 normal controls, 19 ‘‘elbow’’, indicating that there was little added benefit of
PD and nine control subjects were not administered the NPI or increasing the cluster count from 5 to 6. When divided into two
had missing data on more than two items. A further seven samples, 166 of 175 patients (94.8%) were classified in the same
patients were excluded because of possible dementia, leaving clusters, supporting the validity of the cluster solution. Two of
175 PD patients and 166 healthy control subjects for inclusion. the clusters contained only one and two patients and were
The patients had a lower mean MMSE score (27.8 (SD 2.3)) discarded, with three clusters remaining. The majority of
than the control subjects (28.6 (1.5)) (p = 0.001), and slightly patients (n = 158, 90.3%) fell into a cluster with no or very
less years of formal education (10.9 (2.3) vs 11.6 (3.5) years; mild symptoms (cluster 1). Cluster 2 consisted of patients with
p = 0.04) but did not differ significantly regarding age (67.8 (9.0) mood symptoms (n = 10; 5.7%) (ie, high scores on the
vs 67.3 (9.1) years; NS) or sex distribution (58% vs 60% male; depression, anxiety and apathy items) and a final small cluster
NS). 3 (n = 4, 2.3%) consisted of patients with a predominantly high
The NPI scores and proportion with symptoms are shown in apathy score. The three clusters differed significantly in
table 1. The total NPI score (median and interquartile range 1 (6) cognition and motor impairment, with patients in the apathy
vs 0 (0)), number of symptoms (1 (2) vs 0 (0)) and number of cluster being more impaired than the other groups (table 2).
symptoms with a clinically significant severity (0 (1) vs 0 (0))
differed significantly between the groups (all p values ,0.001). DISCUSSION
Ninety-eight (56%) of the PD group had a positive score on at least This study demonstrates for the first time that a characteristic
one item compared with 36 (21.7%) in the control group neuropsychiatric symptom pattern can be found in early drug
(x2 = 42.0, p,0.001). In the PD group, depression (34.3%), apathy naı̈ve patients with PD. More than half of the patients exhibited
(27.4%), sleep disturbance (17.8%) and anxiety (16.4%) were the at least one symptom, and more than 25% had at least one
most common symptoms. The number of positive NPI items was symptom of clinically significant severity. Several patients had
higher in PD patients than in control subjects (z = 27.2, two or more symptoms, and 13% had two or more clinically
p,0.001), with 61 (34.9%) patients having more than one significant symptoms. Depression, anxiety, sleep disturbances
symptom compared with only 10 (6.0%) in the control group. and apathy were the most common symptoms whereas
Forty-seven (26.9%) PD patients had at least one symptom of psychotic symptoms were very rare.
clinical significance, the most common being apathy (11.4%), The cluster analysis identified two neuropsychiatric syn-
depression (10.3%), appetite (8%) and sleep (7.5%) disturbances, dromes, one with mood symptoms and one with predominantly
compared with only five (3.0%) in the control group having a apathy. This observation is consistent with previous studies.
symptom of clinically significant severity (p,0.001). Patients Studies of medium staged PD (ie, Hoehn and Yahr stages 3–4)
with PD had more symptoms of clinically significant severity have reported neuropsychiatric clusters, including depression,
than control subjects (z = 26.1, p,0.001), and 22 (12.6%) PD anxiety and apathy clusters, and a psychosis cluster.8 In a cohort
patients had more than one clinically significant symptom, consisting of patients with advanced PD and dementia, a group
compared with only two (1.2%) in the control group. with agitation and a variety of symptoms was added to the
Patients with at least one clinically significant score had a mood, apathy and psychosis groups.9 Thus the spectrum of
higher UPDRS motor subscale score (29.5 (13.7)) than those neuropsychiatric symptoms tends to widen with more
without clinically significant neuropsychiatric symptoms (21.5 advanced disease. In early PD, mood and apathy are the
(9.7), t = 4.3, p,0.001) whereas the MMSE score or sex predominating neuropsychiatric symptoms. Subsequently, with
distribution did not differ significantly. advancing disease, a group with hallucinations occurs, and in
Short report
later stages with dementia, a group of patients exhibit multiple Thus such symptoms may have been present but not detected.
and severe neuropsychiatric symptoms including agitation. Finally, the NPI assesses only severity of depression and anxiety
The aetiology of neuropsychiatric symptoms in PD is most but provides no formal diagnosis, which would require a
likely multifactorial, with a possible contribution from both structured psychiatric interview.
psychological stress and brain changes associated with PD. At Although the majority of patients with early untreated PD
this early disease stage, the motor symptoms are usually mild did not have clinically significant neuropsychiatric symptoms,
with little functional impairment, but the knowledge of having this study shows that such symptoms are clearly more prevalent
been diagnosed with a chronic progressive and debilitating brain than in controls. We recommend that screening of neuropsy-
disease with a potentially negative effect on their job situation, chiatric symptoms should be performed at the time of diagnosis
economic security and quality of life10 may induce mood of PD. Longitudinal studies are required to explore the predictive
symptoms such as sadness and anxiety. On the other hand, significance of neuropsychiatric symptoms, and how the profile
both depression and anxiety can develop before the onset of of these symptoms evolve with time.
motor symptoms and the diagnosis of PD,11 strongly suggesting
that brain changes occurring early in the disease may render the Funding: This study was funded by the Western Norway Regional Health Authority
(grant No 911218) and the Research Council of Norway (grant No 177966).
patients more likely to develop psychiatric symptoms.
Neuropsychiatric symptoms were associated with cognitive Competing interests: None.
impairment. Care was taken to exclude any patient with Ethics approval: The study was approved by the Regional Committee for Medical
dementia, and thus this finding adds to previous studies in and Health Research Ethics, Western Norway, University of Bergen, Bergen, Norway.
demonstrating a relationship between psychiatric and cognitive
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These include:
References This article cites 13 articles, 6 of which you can access for free at:
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Notes