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BRIEF COMMUNICATION
Body side of motor symptom onset in Parkinson’s disease
is associated with memory performance
M.M. AMICK,
1,2
J. GRACE,
1,2
and K.L. CHOU
3,4
1Department of Medical Rehabilitation, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island
2Department of Psychiatry and Human Behavior, Brown Medical School, Providence, Rhode Island
3Department of Clinical Neurosciences, Brown Medical School, Providence, Rhode Island
4NeuroHealth, Warwick, Rhode Island
(Received December 15, 2005; Final Revision April 19, 2006; Accepted April 20, 2006)
Abstract
The relation of body side of motor symptom onset in Parkinson’s disease (PD) to memory measures associated with
hemispheric dominance was examined. Fourteen patients with right body side motor symptom onset (RPD, inferred
left hemisphere dysfunction) and 16 patients with left side onset (LPD, right hemisphere dysfunction) were
administered measures of verbal (Hopkins Verbal Learning Test-Revised) and visual memory (Brief Visual Memory
Test-Revised), that require similar task demands and are associated with left or right hemisphere dominance,
respectively. The LPD group demonstrated poorer visual than verbal memory, both within group and in comparison
to the RPD group. By contrast, the RPD group showed poorer verbal than visual memory within group. These
findings suggest that side of motor symptom onset is associated with asymmetrical memory dysfunction
(JINS, 2006, 12, 736–740.)
Keywords: Laterality, Dopamine, Learning, Neuropsychology, Movement disorders, Basal ganglia
INTRODUCTION
Parkinson’s disease (PD) typically begins with unilateral
motor symptoms and even with progression of the disease,
the initial body side of motor symptom onset generally
remains more affected (Lee et al., 1995). The asymmetric
motor symptoms observed in PD have been found to be
associated with asymmetrical depletion of dopamine (DA)
in the basal ganglia at autopsy (Kempster et al., 1989).
Studies using single proton emission computed tomogra-
phy (SPECT) imaging have found changes in DA trans-
porter binding contralateral to the side of initial motor
symptoms (Innis et al., 1993). The asymmetry in uptake
persists even after the disease has progressed from unilat-
eral to bilateral motor symptoms (e.g. Antonini et al., 1995).
The asymmetrical subcortical changes that accompany PD
have been linked to dysfunction of certain hemisphere spe-
cific cognitive abilities.
The memory impairments typically observed in PD
patients are characterized by deficits in aspects of memory
requiring executive functions (i.e., learning and delayed free
recall), whereas the process of consolidation is typically
intact (i.e., savings and recognition are not impaired). This
pattern of memory performance contrasts with the impaired
consolidation abilities of patients with Alzheimer’s disease
(reviewed in Pillon et al., 2001).
A relation between lateralized motor symptoms and mem-
ory functions associated with hemispheric dominance has
not been observed consistently. The expected pattern of
impairment with worse performance on verbal memory tasks
by patients with right body side motor symptom onset (RPD,
inferred left hemisphere dysfunction) and poorer perfor-
mance on visuospatial memory tasks by patients with left
side onset (LPD, right hemisphere dysfunction) has been
reported by some studies. For instance, RPD patients showed
worse verbal memory performance than LPD patients, but
both groups demonstrated comparable visual memory per-
formance (Starkstein et al., 1987). By contrast, Blonder and
colleagues (1989) reported that LPD patients performed
worse on a measure of visual memory relative to a control
Correspondence and reprint requests to: Melissa M. Amick, Ph.D.,
Memorial Hospital of Rhode Island, Department of Medical Rehabilita-
tion, 111 Brewster Street, Pawtucket, RI 02860. E-mail: Melissa_Amick@
Brown.edu
Journal of the International Neuropsychological Society (2006), 12, 736–740.
Copyright © 2006 INS. Published by Cambridge University Press. Printed in the USA.
DOI: 10.10170S1355617706060875
736
group but not relative to an RPD subgroup. There also have
been several reports of null findings regarding RPD and
LPD performance on measures of verbal and visual mem-
ory (e.g., St. Clair et al., 1998) and reports that visual and
verbal memory performance differs in LPD and RPD patients
but not in the expected direction. Tomer and colleagues
(1993) found that LPD patients demonstrated poorer per-
formance on measures of verbal learning relative to RPD
patients, but there was no difference in visual memory per-
formance between groups.
Inconsistent findings across studies might be because of
several factors. Studies have used different inclusion crite-
ria such as including patients who may have dementia or
treated with anticholinergic medications. Also, verbal and
visual memory measures were not equivalent in format.
Finally, different methods for measuring motor symptom
laterality have been employed.
The current study examined visual and verbal memory, with
measures requiring similar task demands, in non-demented
PD patients with a specific side of motor symptom onset who
were not treated with anticholinergic medications. We hypoth-
esized that side of motor symptom onset would be associated
with performance on memory tasks requiring predominantly
left or right hemisphere functions. Specifically, it was pre-
dicted that within group LPD patients (inferred right hemi-
sphere dysfunction) would demonstrate greater impairments
on measures of visual than verbal memory, whereas within
group RPD patients (left hemisphere dysfunction) would be
more impaired on measures of verbal than visual memory.
METHODS
Participants
Participants were 30 PD patients (20 men, 10 women)
from a hospital-based Movement Disorders Clinic. Partici-
pants were not demented (DRS scores ⱖ123) (Jurica et al.,
2001). Patients were diagnosed as having idiopathic PD
by a movement disorders specialist based on the following
criteria: presence of 2 out of 3 cardinal PD manifestations
(tremor, bradykinesia, and rigidity) and a good response to
dopaminergic medications. Side of motor symptom onset
was determined by chart review for each participant (based
on patient report and motor examination). Two PD partici-
pants achieved scores .17 on the Beck Depression
Inventory-II (BDI-II) and one participant achieved a score
.7 on the Geriatric Depression Scale-short form. For each
of these participants, inspection of their responses on the
self-report measures indicated that the physical symptoms
of PD were the major cause of elevated scores. Eleven
participants were treated with antidepressants at the time
of their evaluation. To be noted, in two cases there was no
documentation of antidepressant treatment.
Procedure
Data were collected by retrospective chart review. All
patients had participated in a comprehensive neuropsycho-
logical evaluation conducted or supervised by a licensed
clinical neuropsychologist.
Demographic variables included age, education, and gen-
der. Levodopa equivalent doses were calculated for each
participant’s medications (Herzog et al., 2003). Within two
months of the neuropsychological measures, all patients were
evaluated with the Hoehn and Yahr scale and the motor
section of United Parkinson’s Disease Rating Scale. Because
the study is a retrospective chart review, no single global
cognitive screening measure was administered. However
most (n527) received either the DRS or an MMSE. There-
fore, MMSE scores were converted to DRS scores using
the equation derived by Bobholz and Brandt (1993). See
Table 1.
The two memory measures were selected because they
have similar formats (i.e., three learning trials of 12 units of
information and delayed recall 25 minutes later).
Hopkins Verbal List Learning Test—Revised
The Hopkins Verbal List Learning Test—Revised (HVLT-R)
is a test of verbal memory (Brandt & Benedict, 2001). A
12-item word list was presented orally three times. After
each presentation the participants are asked to recall all the
words they can recall from the list. The learning score is
calculated by summing all words learned across the three
trials (max score 536). Delayed recall of the word list
occurs after a 25-minute delay (max score 512).
Table 1. Characteristics of RPD and LPD patients
RPD
(n514)
LPD
(n516) t-value p-value
Dementia Rating Scale 135.0 6.6 134.0 5.0 0.45 0.66
n511
Learning HVLT-R 21.1 6.3 19.6 6.1 0.67 0.51
Learning BVMT-R 21.3 8.2 11.8 6.5 3.52 0.001
Delayed Recall HVLT-R 8.1 3.8 6.8 3.3 0.97 0.34
Delayed Recall BVMT-R 9.1 3.2 4.9 3.4 3.56 .001
Body side of Parkinson’s disease onset and memory 737
Brief Visual Memory Test—Revised
The Brief Visual Memory Test—Revised (BVMT-R) is a
test of visuospatial memory (Benedict, 1997). There are
three learning trials in which six abstract designs are pre-
sented visually for 10 seconds. The learning score is calcu-
lated by summing all designs recalled across the three
encoding trials (max score 536). Delayed recall of the
designs occurred after a 25-minute delay. Recall is scored
by accuracy and correct placement of each figure (max
score 512).
RESULTS
Data Analysis
In order to compare memory performance with a common
metric and to equate tasks for difficulty, each memory score
was converted to a Z-score using published normative data
(Brandt & Benedict, 2001; Benedict, 1997).
To examine the association of body side of motor symp-
tom onset and memory performance, the Z-scores for each
participant were submitted to 2 separate mixed factorial
ANOVAs (one for Learning scores and one for Delayed
Recall scores) with a within-subjects factor of Modality of
Memory Task (verbal, visual) and a between-subjects fac-
tor of Group (LPD, RPD). Independent samples t-tests
compared performance between groups on the BVMT-R
and HVLT-R. In order to evaluate differences on verbal
and visual memory measures within group paired samples
t-tests were conducted.
Participant variables
There was no significant difference (all ps ..05) between
LPD and RPD patients, with respect to age (LPD; M5
66.8, SD 57.5, RPD; M559.9, SD 511.9), education
(LPD; M512.9, SD 52.7, RPD (n513); M515.2, SD 5
3.9), years of illness duration (LPD; M59.3, SD 57.9,
RPD (n513); M58.6, SD 56.2), levodopa equivalent
dose (LPD; M5781.3, SD 5794.0, RPD (n513); M5
1109.2, SD 5652.3), or disease severity (H&Y: LPD;
range 51–4, RPD; range 1–4, UPDRS: LPD (n513); M5
25.4, SD 510.9, RPD (n513); M518.2, SD 516.6).
Four of the LPD patients and two of the RPD patients
were left handed. While handedness is typically associated
with dominance of language in the contra-lateral hemi-
sphere, which could have impacted our findings, we observed
that the means of the left-handed participants did not differ
from the right-handed participants within group (all ps .
.15). Raw scores for performance on the HVLT-R and the
BVMT-R are included in Table 1.
Learning
There was a main effect of Group (F[1, 28] 56.2, p5.02),
because the LPD group performed more poorly on mea-
sures of learning relative to the RPD group. The main effect
of Modality of Memory Task was not significant (F[1, 28] 5
0.21, p..6). Most important for our hypotheses, the inter-
action of Group 3Modality of Memory Task was signifi-
cant [F(1, 28) 512.4, p5.002] .
To examine this significant interaction, one-tailed t-tests
were conducted as the direction of effects was predicted a
priori. Between groups, the LPD and RPD groups had com-
parable Learning scores on the HVLT-R [t(28) 5.46, p.
.6]. Consistent with our hypothesis, the LPD group demon-
strated significantly poorer learning scores on the BVMT-R
than the RPD group [t(28) 53.9, p5.001] (Fig. 1).
Within group differences were compared with one-tailed
paired samples t-tests. As predicted and most critical to our
Fig. 1. LPD and RPD patients demonstrate different patterns of memory performance on the
BVMT-R and the Hopkins HVLT-R. Columns represent average Z-scores. Error bars represent
standard error of the mean.
738 M.M. Amick et al.
hypotheses, the LPD patients demonstrated poorer visual
relative to verbal memory [t(15) 52.4, p5.02] . By con-
trast, RPD patients showed poorer verbal relative to visual
memory [t(13) 52.6, p5.01] (Fig. 1).
Delayed recall
Similar to the results for the Learning scores, there was a
main effect of Group (F[1,28] 56.9, p5.01) but not the
main effect of Modality of Memory Task ( F[1, 28] 50.4,
p.0.5). Consistent with our predictions, again the inter-
action of Group 3Modality of Memory Task was signifi-
cant (F[1, 28] 510.5, p5.003).
Between groups, the LPD and RPD groups had compa-
rable Delayed Recall scores on the HVLT-R [t(28) 5.97,
p..3], whereas the LPD group had significantly poorer
Delayed Recall scores on the BVMT-R than the RPD group
[t(28) 53.7, p5.001] (Fig. 1). Again supporting our hypoth-
eses, within group the LPD patients demonstrated poorer
visual relative to verbal memory [t(15) 51.7, p5.05] . By
contrast, RPD patients showed poorer verbal relative to visual
memory [t(13) 53.2, p5.004] (Fig. 1).
DISCUSSION
The results from the current study indicate that body side of
motor symptom onset is associated with performance on
memory measures. The strongest support for this statement
was obtained from our within group comparisons, which
found that, the LPD group (inferred right hemisphere dys-
function) showed poorer visual learning and delayed recall
(associated with right hemisphere functions) relative to their
verbal memory functions (associated with left hemisphere
functions). By contrast, within group the RPD patients
(inferred left hemisphere dysfunction) had poorer verbal
memory compared to their visual memory. The current find-
ings emphasize the importance of considering body side of
motor symptom onset when evaluating PD patients’ mem-
ory performance.
Side of motor symptom onset is not always considered in
research examining cognition in PD patients. Postle and
colleagues (1997) found that PD patients demonstrated
poorer performance on a task of spatial (associated with
greater right hemisphere involvement) relative to object
working memory (greater left hemisphere involvement).
Whereas the authors reported that side of motor symptom
onset was not associated with performance on measures of
spatial working memory, it is possible that their results were
influenced by the over inclusion of LPD (n511) compared
to RPD patients (n54). Side of motor symptom onset may
not fully account for previous reports of preferentially
impaired visuospatial working memory, but on tasks that
are associated with hemispheric dominance, we suggest that
side of motor symptom be thoroughly considered.
Previous work in this area has focused on patients with
hemi-parkinsonism (unilateral involvement only) or used
involved methods for measuring symptom laterality. In this
study, side of motor symptom onset was determined by
chart review alone and many PD patients had already pro-
gressed to bilateral involvement; yet significant differences
were still observed. Consequently, the effect of side of motor
symptom onset is likely pervasive as it is observed even
after the disease has begun to affect both hemispheres. The
present findings emphasize that side of motor symptom onset
can be reliably documented by chart review and0or patient
and caregiver reported medical history, information that is
frequently available for most neuropsychological evaluations.
In the current study commonly used measures of verbal
(HVLT-R) and visual (BVMT-R) memory were selected to
assess the integrity of left and right hemisphere functions in
PD patients. It should be recognized that these measures
differ, because the visuospatial task also includes a motor
component (construction). We addressed the issue of differ-
ences in task difficulty by converting all raw scores to
z-scores, based on published normative data. Motor symp-
toms do not account for our findings because the group
with greater right hand involvement (RPD group) demon-
strated poorer performance on measures of verbal memory
compared to their visual memory performance. The present
findings provide evidence of the construct validity of the
HVLT-R and BVMT-R as measures of left and right hemi-
sphere functioning, respectively.
The impact of dopamine replacement therapy on our
results should be mentioned. The LPD group performed in
the impaired range on all memory measures compared to
the normative sample, whereas the RPD group performed
in the impaired range only for verbal learning. Whereas not
significant, the LPD group had higher UPDRS scores and
were treated with less dopaminergic medications compared
to the RPD group. It is possible that the differences in over-
all performance are related to suboptimal treatment of the
LPD patients, and this may explain why there was no sig-
nificant difference between groups on the HVLT-R mea-
sures and large differences on the BVMT-R measures. If
optimally treated it might be speculated that the LPD group
performance would improve and potentially lead to signif-
icant between group differences for all memory measures.
Despite possible differences in the management of PD symp-
toms, within group we found asymmetrical memory perfor-
mance in the expected directions. Future studies are needed
to examine the association between side of motor symptom
onset and performance on cognitive tasks requiring lateral-
ized cognitive functions in PD patients both off and on their
medications.
Neuroimaging studies reveal that there is an asymmetri-
cal loss of dopamine within the basal ganglia associated
with side of motor symptom onset. It is believed that the
basal ganglia influence cognition through closed circuits
formed with the frontal lobes (Middleton & Strick, 2000a;
2000b). Research focused on describing basal ganglia-
thalamo-cortical circuits have revealed three distinct closed
loops involving frontal regions (Middleton & Strick, 2000a;
2000b). Studies of cognition in PD have attributed deficits
on memory tasks requiring encoding and free recall to the
Body side of Parkinson’s disease onset and memory 739
disruption of these basal ganglia-thalamo-frontal circuits (see
Pillon et al. for review). Our results suggest that side of motor
symptom onset may be associated with dysfunction of the
contralateral basal ganglia-thalamo-frontal circuits. Neuro-
imaging addressing the association of side of motor symp-
tom onset and performance on cognitive tasks requiring
hemispheric dominance would add greatly to the understand-
ing of the neurocognitive changes associated with PD.
In conclusion, LPD patients demonstrated greater impair-
ments in visual than verbal memory both within group and
in comparison to the RPD group, whereas within group the
RPD patients showed greater impairments in verbal than
visual memory. These findings emphasize that body side of
motor symptom onset is a critical factor to consider when
evaluating PD patients’ cognitive performance. Inattention
to side of motor symptom onset may lead to an inaccurate
description of the cognitive impairments associated with
this disease.
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