Cognitive impairment in Parkinson's disease.
ABSTRACT Cognitive impairment plays a role in Parkinson's disease (PD) and has important consequences for patient management. However, many aspects of cognitive impairment in PD remain unclear because of the use of different and often invalid measurement instruments. In this study, a reliable and valid instrument, the SCales for Outcomes in PArkinson's disease-COGnition (SCOPA-COG), was used.
To evaluate cognitive functioning in a large cohort of patients with Parkinson's disease and to assess the relations with demographic, disease related and clinical variables.
A cohort of 400 patients with PD was evaluated for cognition, motor and non-motor domains, as well as for demographic and disease related characteristics. Results were compared with 150 controls matched for overall age, sex and education distribution.
Patients with PD scored significantly lower on all cognitive subdomains compared with controls, with the largest differences for executive functioning and memory. After correction for age and years of education, 22% of patients had impaired cognition, as measured by the total SCOPA-COG score, compared with controls. Across all patients, more severe cognitive impairment was associated with significantly more impairment in motor, autonomic, depressive and psychotic domains. Patients with the postural instability gait difficulty (PIGD) dominant phenotype showed more cognitive impairment compared with patients with the tremor dominant phenotype. Contrary to tremor scores, PIGD scores significantly worsened with increasing disease severity.
Cognition is an important domain of the clinical spectrum of PD and poorer cognitive performance is associated with greater impairment in motor and non-motor domains in PD. The difference in cognitive scores between PIGD dominant patients and tremor dominant patients likely reflects more advanced disease.
- SourceAvailable from: Dimitrios KasselimisArch Neurosci. 01/2015; 2(3):e21087.
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ABSTRACT: Individuals with mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene are at significantly high risk of developing Parkinson's disease with cognitive deficit. We examined whether visual short-term memory impairments, long associated with patients with Parkinson's disease, are also present in GBA-positive individuals-both with and without Parkinson's disease. Precision of visual working memory was measured using a serial order task in which participants observed four bars, each of a different colour and orientation, presented sequentially at screen centre. Afterwards, they were asked to adjust a coloured probe bar's orientation to match the orientation of the bar of the same colour in the sequence. An additional attentional 'filtering' condition tested patients' ability to selectively encode one of the four bars while ignoring the others. A sensorimotor task using the same stimuli controlled for perceptual and motor factors. There was a significant deficit in memory precision in GBA-positive individuals-with or without Parkinson's disease-as well as GBA-negative patients with Parkinson's disease, compared to healthy controls. Worst recall was observed in GBA-positive cases with Parkinson's disease. Although all groups were impaired in visual short-term memory, there was a double dissociation between sources of error associated with GBA mutation and Parkinson's disease. The deficit observed in GBA-positive individuals, regardless of whether they had Parkinson's disease, was explained by a systematic increase in interference from features of other items in memory: misbinding errors. In contrast, impairments in patients with Parkinson's disease, regardless of GBA status, was explained by increased random responses. Individuals who were GBA-positive and also had Parkinson's disease suffered from both types of error, demonstrating the worst performance. These findings provide evidence for dissociable signature deficits within the domain of visual short-term memory associated with GBA mutation and with Parkinson's disease. Identification of the specific pattern of cognitive impairment in GBA mutation versus Parkinson's disease is potentially important as it might help to identify individuals at risk of developing Parkinson's disease.Brain 06/2014; · 10.23 Impact Factor
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ABSTRACT: Delayed adjustment tasks have recently been developed to examine working memory (WM) precision, that is, the resolution with which items maintained in memory are recalled. However, despite their emerging use in experimental studies of healthy people, evaluation of patient populations is sparse. We first investigated the validity of adjustment tasks, comparing precision with classical span measures of memory across the lifespan in 114 people. Second, we asked whether precision measures can potentially provide a more sensitive measure of WM than traditional span measures. Specifically, we tested this hypothesis examining WM in a group with early, untreated Parkinson's disease (PD) and its modulation by subsequent treatment on dopaminergic medication. Span measures correlated with precision across the lifespan: in children, young, and elderly participants. However, they failed to detect changes in WM in PD patients, either pre- or post-treatment initiation. By contrast, recall precision was sensitive enough to pick up such changes. PD patients pre-medication were significantly impaired compared to controls, but improved significantly after 3 months of being established on dopaminergic medication. These findings suggest that precision methods might provide a sensitive means to investigate WM and its modulation by interventions in clinical populations.Journal of Neuropsychology 09/2014; · 3.82 Impact Factor
Cognitive impairment in Parkinson’s disease
D Verbaan, J Marinus, M Visser, S M van Rooden, A M Stiggelbout, H A M Middelkoop, J J van Hilten
............................................................... ............................................................... .....
See end of article for
D Verbaan, Department of
Neurology, K5Q-92, Leiden
University Medical Centre,
PO Box 9600, NL- 2300 RC
Leiden, the Netherlands; D.
Received 1 December 2006
Revised 7 March 2007
Accepted 19 March 2007
Published Online First
18 April 2007
J Neurol Neurosurg Psychiatry 2007;78:1182–1187. doi: 10.1136/jnnp.2006.112367
Background: Cognitive impairment plays a role in Parkinson’s disease (PD) and has important consequences
for patient management. However, many aspects of cognitive impairment in PD remain unclear because of
the use of different and often invalid measurement instruments. In this study, a reliable and valid instrument,
the SCales for Outcomes in PArkinson’s disease-COGnition (SCOPA-COG), was used.
Aim: To evaluate cognitive functioning in a large cohort of patients with Parkinson’s disease and to assess the
relations with demographic, disease related and clinical variables.
Methods: A cohort of 400 patients with PD was evaluated for cognition, motor and non-motor domains, as
well as for demographic and disease related characteristics. Results were compared with 150 controls
matched for overall age, sex and education distribution.
Results: Patients with PD scored significantly lower on all cognitive subdomains compared with controls, with
the largest differences for executive functioning and memory. After correction for age and years of education,
22% of patients had impaired cognition, as measured by the total SCOPA-COG score, compared with
controls. Across all patients, more severe cognitive impairment was associated with significantly more
impairment in motor, autonomic, depressive and psychotic domains. Patients with the postural instability gait
difficulty (PIGD) dominant phenotype showed more cognitive impairment compared with patients with the
tremor dominant phenotype. Contrary to tremor scores, PIGD scores significantly worsened with increasing
Conclusions: Cognition is an important domain of the clinical spectrum of PD and poorer cognitive
performance is associated with greater impairment in motor and non-motor domains in PD. The difference in
cognitive scores between PIGD dominant patients and tremor dominant patients likely reflects more advanced
PD is much broader, also encompassing many non-motor
domains, including cognition.1Cognitive decline is a predictor
of dementia in PD (PDD),2 3which has important consequences
for patient management.2 4 5
dementia in PD varies greatly (2–81%) between studies.3
Consistency in the relation between cognitive impairment/
PDD and demographic or clinical characteristics has only been
found for age and motor impairment. Factors that have
contributed to the variability between studies are sample
characteristics (selection procedure, source population, sample
size), applied criteria of dementia and cognitive impairment
and the use of different methods for the evaluation of cognition
in PD. Most studies to date have been performed on small
populations and samples selected from tertiary care clinics.
Additionally, several studies in PD have relied on the use of
measurement instruments that have been developed for
screeningof dementia (Mini-Mental
(MMSE)) or Alzheimer’s disease. These instruments generally
lack discriminative ability to capture the specific aspects of
cognitive impairment in PD. Moreover, many of these instru-
ments include items that are sensitive to motor symptoms and
may thus affect the results of cognitive assessment in PD.
Based on compelling evidence that memory, attention and
executive and visuospatial functioning are important aspects of
cognitive impairment in PD, a reliable and valid quantitative PD
specific instrument (SCales for Outcomes in PArkinson’s
disease-COGnition (SCOPA-COG)) was developed in 2003.6In
the current study, we used this instrument to evaluate the
characteristics of cognitive impairment in patients with PD and
its associations with demographic and clinical characteristics.
arkinson’s disease (PD) is predominantly characterised as
a movement disorder, but over the past years there has
been an increasing awareness that the clinical spectrum of
The reported prevalence of
The study is part of the PROfiling PARKinson’s disease
(PROPARK) study, a longitudinal cohort study of patients with
PD, who are extensively profiled on phenotype, disability and
global outcomes of health, with assessment instruments that
have been found to be valid and reliable in PD. Findings
obtained from the first annual evaluation of 408 patients who
were assessed between May 2003 and September 2005 were
used in this analysis.
Patients with idiopathic PD were recruited from neurology
clinics from both university and regional hospitals in the
western region of the Netherlands. All patients were diagnosed
by neurologists with a special interest in PD according to the
clinical diagnostic criteria of the United Kingdom Parkinson’s
Disease Society Brain Bank for idiopathic PD.7Patients were
stratified according to age at onset (based on age at onset of the
first symptoms as perceived by the patient (/.50 years) and
disease duration ((/.10 years), because these characteristics
are important determinants of disease course in PD.8 9Inclusion
of patients stopped when approximately 100 patients were
included in each stratum. No other selection criteria were
applied. No attempt was made to separate demented from non-
demented patients according to the DSM-IV-criteria.10The
majority of the patients were assessed at the Leiden University
Abbreviations: H&Y, Hoehn and Yahr; MMSE, Mini-Mental State
Examination; PD, Parkinson’s disease; PDD, dementia in PD; PIGD,
postural instability gait difficulty; PROPARK study, PROfiling PARKinson’s
disease study; SCOPA-COG, SCales for Outcomes in PArkinson’s disease-
Medical Centre. To avoid a bias towards recruiting less severely
affected patients, those who were unable to come to the
hospital for the assessment were assessed at home.
Controls were selected to match the overall age, sex and
education distribution of the patients and were included if they
had no documented diseases of the central nervous system and
were able to read and understand Dutch. Half of the controls
(n=75) were acquaintances from participating patients and
the other controls were recruited from volunteers working in
our hospital. The study was approved by the local medical
ethics committee of the Leiden University Medical Centre and
all participants gave informed consent.
In the PROPARK study, all patients had a standardised
assessment, including evaluation of demographic and clinical
Measurement instruments for the different clinical domains
of PD were derived from a prior project (SCales for Outcomes in
PArkinson’s disease (SCOPA)).11For the current study, data
obtained for cognition (SCOPA-COG,6MMSE12), depressive
symptoms (Beck Depression Inventory13), autonomic function
(SCOPA-AUT14), motor function (SPES-SCOPA-motor15), dis-
ease severity (Hoehn and Yahr (H&Y)16) and psychotic
symptoms (modified Parkinson Psychosis Rating Scale17) were
used. All patients who used levodopa or dopamine agonists and
experienced motor fluctuations were assessed during the ‘‘on’’
state. Data collected from controls included demographic
characteristics and cognition scores.
All instruments were either self-administered or adminis-
tered by one of three trained research associates. The SCOPA-
COG has 10 items, including memory (four items: replicating
the order in which cubes were pointed out, digit span
backward, immediate and delayed word recall), attention
(two items: counting down by threes and months backward),
executive functioning (three items: successive repetitions of
fist-edge-palm movements, set shifting with dices and fluency
animals) and visuospatial functioning (one item: mental
reconstruction of figures). The maximum score is 43. Values
of all rating scales are expressed as percentages of the
maximum obtainable score (100%) for reasons of compar-
ability. Except for the SCOPA-COG and the MMSE, higher
scores indicate more severe impairment.
The association between motor phenotype (tremor or
postural instability gait difficulty (PIGD)) and cognition
was also evaluated. A mean score for tremor was calculated
as the mean of the following items from the SPES-SCOPA-
motor: rest tremor (right and left) and postural tremor (right
and left) and a mean score for PIGD was calculated as the
mean of postural instability, freezing during ‘‘on’’, gait and
walking. Patients with a ratio of mean tremor score/mean
PIGD score >1.5 were classified as tremor dominant whereas
patients with a ratio of (1.0 were classified as PIGD
dominant. Patients with ratios between .1.0 and ,1.5 were
classified as indeterminate.
If 25% or more of the data from a particular scale were missing,
this scale was excluded from statistical analyses for that
patient. Linear regression and correlation coefficients were
used to assess relations between SCOPA-COG scores and
demographic, disease related and clinical characteristics. In
the linear regression analysis, the forward method was used.
For patients, three separate blocks were used in the model:
block 1 (age, sex and years of education), block 2 (age at onset,
levodopa dose and motor function) and block 3 (depressive
symptoms and psychotic symptoms). Linear regression for
blocks 1 and 2 was used to determine the separate contribution
of demographic and disease related variables. In block 3, the
additional contribution of depressive and psychotic symptoms
to the variance of the SCOPA-COG total score was explored.
A Student’s t test for independent samples was used to assess
differences in age and years of education between patients and
controls, and a x2test was used to assess differences in sex
distribution between patients and controls. Subsequently,
SCOPA-COG scores of patients and controls were compared
with the Student’s t test for independent samples, whereas
differences between groups based on disease severity were
compared by analysis of covariance.
To compare differences in subdomain scores between
patients and controls, standardised z score values were
calculated to account for differences in variance between the
subdomains. Z scores were also used to account for differences
in difficulty levels between subdomains.
Subgroups of patients with normal or impaired cognition
were constructed with the following approach:
Characteristics of the participants
Men (n (%))
Age (y) (mean (SD))
Education (y) (mean (SD))
Disease duration (y) (mean (SD))
Age at onset (y) (mean (SD))
Hoehn and Yahr stage (n (%))*
Levodopa therapy (n (%))
Levodopa dose (mg/day) (mean (SD))
Dopamine agonists therapy (n (%))
Cholinesterase inhibitors (n (%))
No antiparkinson treatment (n (%))
*Sum of percentages does not equal 100 because of rounding off.
`Student’s t test for independent samples results.
Cognitive impairment in Parkinson’s disease1183
(1) Because age and education are known to have an influence
on cognition,18the regression equation of the SCOPA-COG
score of controls with the variables age and years of
education was used to calculate an estimated value for
every subject (controls and patients).
(2) The difference (D) between the actual value and the
estimated value was calculated for every subject (controls
(3) Patient subgroups were formed on the basis of the
distribution of the D value of the controls. This resulted
in two subgroups:
(a)normal cognition; D value of 2/+2 SD of the data of
impaired cognition; D value (22 SD of the data of
To analyse differences between patients with normal and
impaired cognition, the Student’s t test for independent samples
and the x2tests were used without adjusting for other variables.
To evaluate how different impairment domains relate to each
other, patients were classified into subgroups, based on the
quartiles of the SCOPA-COG scores, with the first quartile
representing the highest and the fourth quartile the lowest
scores. Ordinal regression19was subsequently used to analyse
the relation between SCOPA-COG scores and scores of the other
PD domains. A p value ,0.05 was considered significant. All
analyses were performed using the Statistical Package for the
Social Sciences 12.0.1 Software (SPSS 12.0.1).
Characteristics of the participants
Eight patients with PD were excluded because of too many
missing values on the SCOPA-COG. Consequently, 400 patients
(63% men) and 150 controls (55% men) were included in the
study. No significant demographic differences existed between
patients and controls (table 1).
Influence of demographic, disease related and clinical
The following regression equation best fitted the SCOPA-COG
scores of controls:
SCOPA-COG score=74.6–0.36[age] +0.96[years of educa-
where 74.6 is a constant and age and years of education of each
control are entered in the equation, thus resulting in a predicted
score for each subject.
Age and years of education accounted for 22% of the variance
in controls (p,0.001).
In patients, the total variance of the SCOPA-COG accounted
for by the regression model was 41%. Age and years of
education explained 29% of the variance whereas levodopa dose
and motor function explained an additional 6%. Psychotic
symptoms accounted for another 6% of the total SCOPA-COG
score (p,0.001). Sex, age at onset and depressive symptoms
did not contribute significantly to the explained variance of the
SCOPA-COG. Correlations between the total SCOPA-COG score
and other impairment domain scores were all moderate (motor
function 20.35, psychotic symptoms 20.33, autonomic func-
tion 20.28, depressive symptoms 20.24).
Characteristics of the cognitive profile
Both patients and controls had their lowest scores on the
executive functioning and memory subdomains of the SCOPA-
COG, with the poorest performance in the latter subdomain
(fig 1). Controls performed significantly better than patients on
the SCOPA-COG, each of its subdomains and the MMSE. The
differences between patients and controls were largest for
executive functioning (mean score patients 74% vs mean score
controls 87% (mean z score difference 0.8, 95% CI 0.6 to 0.9))
and memory (mean score patients 42% vs mean score controls
52% (mean z score difference 0.6, 95% CI 0.4 to 0.7)). The
differences for attention (mean score patients 84% vs mean
score controls 92% (mean z score difference 0.3, 95% CI 0.2 to
0.5)) and for visuospatial functioning (mean score patients 85%
vs mean score controls 91% (mean z score difference 0.3, 95%
CI 0.2 to 0.5)) were smaller (all p values ,0.001).
Influence of disease severity
To explore the influence of disease severity, four groups based
on the H&Y stages were compared with respect to cognition
scores corrected for age and sex (controls were classified as
‘‘none’’ (H&Y-stage 0) (n=150), patients in H&Y-stages 1 and
2 were classified as ‘‘mild’’ (n=208), patients in stage 3 as
and SDs for patients and controls expressed as percentages of the
maximum score on the SCales for Outcomes in PArkinson’s disease-
COGnition (SCOPA-COG) (and subdomains) and the Mini Mental State
Examination (MMSE). A higher score indicates better performance.
Cognitive scores in patients and controls. Mean group scores
SDs expressed as percentages of the maximum score on the SCales for
Outcomes in PArkinson’s disease-COGnition (SCOPA-COG). A higher
score indicates better performance. Groups are based on Hoehn and Yahr
(H and Y) stage (stages 1 and 2=mild; stage 3=moderate; stages 4 and
5=severe). Controls are classified as ‘‘none’’ (H and Y stage 0). The
percentages in the bars reflect the proportion of participants in each group
with impaired cognition.
Cognitive scores and disease severity. Mean group scores and
1184 Verbaan, Marinus, Visser, et al
‘‘moderate’’ (n=114) and patients in stages 4 and 5 as
‘‘severe’’ (n=74)). Controls performed significantly better
compared with all three patient groups on the SCOPA-COG.
Severely affected patients performed significantly worse com-
pared with mildly and moderately affected patients (fig 2).
Subgroup analysis of patients grouped by cognitive
Using the distribution of the D value (difference between
SCOPA-COG actual and estimated value) of the controls, 88
(22%) of the patients had impaired cognition. These patients
were significantly older, had an older age at onset, longer
disease duration and used a higher dose of levodopa per day.
Additionally, these patients were more severely affected, as
measured by H&Y, motor, autonomic, depressive and psychotic
scores (fig 2, table 2).
A total of 50 patients (58%) with impaired cognition, as
measured by the SCOPA-COG, had normal MMSE scores based
on age and education corrected normative data. These MMSE
cutoff points were the lower quartile scores of different age and
education groups (total 18 056 subjects).20Fourteen per cent of
the patients with impaired cognition had a disease duration of
less than 5 years.
Across the four quartiles of the SCOPA-COG, increasing
cognitive impairment was associated with significantly higher
impairment scores of motor and non-motor domains (motor,
autonomic and psychotic scores (all p values ,0.001);
depressive scores (p=0.006)) (fig 3). Across groups with
increasing cognitive impairment, the number of PIGD domi-
nant patients significantly increased whereas the number of
tremor dominant patients significantly decreased (p,0.001).
As the assignment of the phenotype was based on the ratio, we
also considered the nominator and denominator individually.
We found that the mean tremor scores did not differ between
the quartiles whereas the mean PIGD scores significantly
increased across the quartiles (from 6% in the first quartile to
11% in the fourth quartile) (trend p,0.001). Contrary to tremor
scores (r=0.1, p=0.070), PIGD scores (r=0.7, p,0.001)
correlated with disease severity, as measured by H&Y.
In this study, a large sample of patients with PD was assessed
with an instrument that evaluates relevant aspects of cognitive
impairment in PD without being sensitive to motor symptoms.6
The findings of this study, however, should be viewed against
the following background. Firstly, this is a clinic based study
with a selection procedure based on age at onset and disease
duration. Therefore, the results in this study cannot be
generalised to the PD population in general. The percentage
of patients with impaired cognition in this study cannot be
interpreted as a prevalence estimate, which limits the possibi-
lity to compare our findings with prevalence rates of other
studies. Secondly, the cross sectional design makes it impos-
sible to draw conclusions about the direction of the reported
In many studies on cognitive functioning in PD, the MMSE is
applied as a gross measure of cognitive impairment.21The
MMSE includes items from domains which generally are less
Characteristics of subgroups of patients with normal or impaired cognition
Men (n (%))
Age (y) (mean (SD))
Education (y) (mean (SD))
Disease duration (y) (mean (SD))
Age at onset (y) (mean (SD))
Hoehn and Yahr stage (n (%))?
Levodopa therapy (n (%))
Levodopa dose (mg/day) (mean (SD))
Dopamine agonists therapy (n (%))
Anticholinergics (n (%))
SCOPA-COG score (mean (SD))
MMSE score (mean (SD))
SPES-SCOPA motor score (mean (SD))
SCOPA-AUT score (mean (SD))
BDI score (mean (SD))
mPPRS score (mean (SD))
30.4 (10.8) 37.6 (12.7)t=4.857, p,0.001?
25.2 (12.0) 29.2 (13.0)t=22.736, p=0.007?
15.5 (10.2) 19.1 (11.8)t=22.787, p=0.006?
10.3 (9.7)18.0 (13.5)t=24.988, p,0.001?
BDI, Beck Depression Inventory; MMSE, Mini-Mental State Examination; mPPRS, modified Parkinson Psychosis Rating
Scale; SCOPA-AUT, SCales for Outcomes in PArkinson’s disease-autonomic function; SCOPA-COG, SCales for
Outcomes in PArkinson’s disease-COGnition.
*Numbers do not add up to group total because of missing values.
?Sum of percentages does not equal 100 because of rounding off.
`Absolute value transformed to 0–100 scale.
?Student’s t test for independent sample results.
Cognitive impairment in Parkinson’s disease 1185
severely affected in PD (temporal orientation and language),3 22
whereas the SCOPA-COG focuses on domains which are
frequently affected in PD (memory, attention and executive
and visuospatial functioning).6Therefore, the SCOPA-COG is
expected to be more sensitive to the cognitive deficits of PD.
This is demonstrated by the fact that in our study 58% of the
patients with abnormal SCOPA-COG scores had normal MMSE
scores. In this comparison, both scores were corrected for age
and years of education, indicating that the MMSE may
substantially underestimate the degree of cognitive impairment
In comparison with controls, all four cognitive subdomains
were impaired in patients. In accordance with other studies,
executive functioning was most prominently affected, followed
by memory.3 23Both controls and patients had relatively low
scores on the memory subdomain, indicating that items of this
subdomain are more difficult compared with items of the other
subdomains. As with other measures of cognition, we found
that age3 5 23–27and (years of) education25 28were related to the
SCOPA-COG scores in both controls and patients. In line with
other studies, more advanced disease (higher H&Y stage, higher
SPES-SCOPA motor score) was associated with poorer cognitive
performance,2 3 5 6 24 28–30indicating an additional influence of
the disease process on cognitive performance. Additionally, in
agreement with others,3 24 26we found that the psychotic
domain score was weakly associated with the total SCOPA-
In daily practice, differences in levels of cognitive impairment
suggest that there are subgroups of particular PD phenotypes.31
Therefore, an attempt was made to identify patients with
impaired cognition by taking into account the influence of age
and education. Using this approach, 22% of the patients had
impaired cognition. Because of the cross sectional design of this
study, we cannot exclude the fact that some patients had a
decline over time in cognitive performance but still remained
within the 95% confidence interval. Longitudinal research is
needed to elucidate whether subgroups of PD patients exist
where cognition is spared, or whether inter-patient variability is
mainly explained through differences in the rate of progression
of the disease.
In this study, 14% of patients with impaired cognition had a
disease duration less than 5 years. Generally it is assumed that
cognitive impairment may develop early in the disease
process,32 33but clinical symptoms of dementia, as detailed in
the DSM-IV criteria, appear only late in the disease course.4 28 30
However, in PD, the term ‘‘dementia’’ is problematic because
there is no disease specific definition3 21and the DSM-IV-
criteria10require experienced disability in daily life, which poses
a problem for any disease where motor impairment per se may
cause such disability.3To determine if patients with impaired
cognition truly suffer dementia, a PD specific definition of
dementia is required. In view of the fact that no adequate
definition of dementia in PD was available, we made no
attempt to distinguish demented from non-demented patients.
Our results show that poorer cognitive performance is
associated with more severe impairments in other domains of
PD. In line with the findings of others, we found that patients
with a tremor dominant phenotype showed higher cognition
scores compared with patients with the PIGD dominant
phenotype.34 35However, since the assignment of this particular
subgroups of patients based on quartiles of
SCales for Outcomes in PArkinson’s disease-
COGnition (SCOPA-COG) scores. 1st–4th
quartile, mild–severe problems. Mean group
scores expressed in percentages of
maximum scores for (A–D): autonomic
impairment (SCOPA-AUT), depressive
symptoms (Beck Depression Inventory (BDI)),
motor function (SPES-SCOPA-motor) and
psychotic symptoms (modified Parkinson
Psychosis Rating Scale (modified-PPRS)).
Higher scores indicate worse performance.
(A–D) Clinical characteristics of
1186Verbaan, Marinus, Visser, et al
phenotype is based on a ratio, we evaluated the differential
influences of the nominator and denominator. We found that
this ratio is only driven by the denominator (PIGD score), and
hence reflects increasing disease progression. According to
Braak and colleagues,36the symptoms of PD parallel the
formation of Lewy bodies and Lewy neurites, and advance in
a topographically predictable sequence beginning in the
medulla oblongata/pontine tegmentum and olfactory bulb/
anterior olfactory nucleus with a subsequent spread to the
substantia nigra and other midbrain nuclei, forebrain and
neocortex. However, the clinical findings may also be explained
by a differential individual vulnerability of neuronal circuits for
the underlying disease process.37As such, neuronal circuits
underlying all impairment domains in PD may be affected
simultaneously, but because of different cell type vulnerability,
become clinically manifest at different stages.
D Verbaan, J Marinus, M Visser, S M van Rooden, J J van Hilten,
Department of Neurology, Leiden University Medical Centre, Leiden, the
A M Stiggelbout, Department of Medical Decision Making, Leiden
University Medical Centre, Leiden, the Netherlands
H A M Middelkoop, Department of Neuropsychology, Leiden University
Medical Centre, Leiden, the Netherlands
Funding/support: This work was supported by grants from the Prinses
Beatrix Fonds (PBF, project No WAR05-0120), the Netherlands
Organisation of Scientific Research (NWO, project No 0940-33-021),
the van Alkemade-Keuls Foundation and the Dutch Parkinson’s Disease
Competing interests: None.
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