Individual cognitive change after DBS-surgery in Parkinson’s disease patients using Reliable Change Index Methodology
Individual cognitive change after DBS-surgery in Parkinson's disease patients using Reliable Change Index Methodology
Thomas Foki 0 1 2
Daniela Hitzl 0 1 2
Walter Pirker 0 1 2
Klaus Novak 0 1 2
Gisela Pusswald 0 1 2
Johann Lehrner 0 1 2
0 T. Foki , M.D. ? D. Hitzl, M.D. ? W. Pirker, M.D. ? G. Pusswald, Ph.D. ? Assoc. Prof. PD Mag. Dr. J. Lehrner , Ph.D. ( ) Department of Neurology, Medical University of Vienna , Wa?hringer Gu?rtel 18-20, 1097 Vienna , Austria
1 K. Novak, M.D. Department of Neurosurgery, Medical University of Vienna , Vienna , Austria
2 W. Pirker, M.D. Department of Neurology , Wilhelminenspital Wien, Vienna , Austria
Summary Long-term therapy of Parkinson's disease (PD) with levodopa (L-DOPA) is associated with a high risk of developing motor fluctuations and dyskinesia. Deep brain stimulation (DBS) in PD patients of the subthalamic nucleus can improve these motor complications. Although the positive effect on motor symptoms has been proven, postoperative cognitive decline has been documented. To tackle the impact of PD-DBS on cognition, 18 DBS patients were compared to 25 best medically treated Parkinson's patients, 24 Mild Cognitive Impairment (MCI) patients and 12 healthy controls using the Neuropsychological Test Battery Vienna-long (NTBV-long) for cognitive outcome 12 months after first examination. Reliable change index methodology was used. Overall, there was cognitive change in individual patients, but the change was very heterogeneous with gains and losses. Further research is needed to identify the mechanisms that lead to improvement or deterioration of cognitive functions in individual cases.
Parkinson; Deep brain stimulation; Cognition; Nucleus subthalamicus
Individuelle kognitive Ver?nderungen untersucht mittels Reliable Change Index Methodology nach DBS-Operation bei Parkinson-Patienten
Zusammenfassung Die Langzeittherapie der
Parkinson-Krankheit mit Levodopa (L-DOPA) ist mit
einem hohen Risiko f?r die Entwicklung motorischer
Fluktuationen und Dyskinesien verbunden. Die tiefe
Hirnstimulation des Nucleus subthalamicus bei
Parkinson-Patienten (PD-DBS) kann diese motorischen
Komplikationen verbessern. Obwohl der positive
Effekt auf die motorischen Symptome nachgewiesen
wurde, wurden postoperative kognitive
Verschlechterungen dokumentiert. Um den Einfluss von
PDDBS auf die Kognition zu untersuchen, wurden 18
DBS-PD-Patienten mit 25 am besten medizinisch
behandelten PD-Patienten, 24 Patienten mit leichter
kognitiver Beeintr?chtigung (MCI) und 12 gesunden
Kontrollpersonen 12 Monate nach der ersten
Untersuchung mittels der neuropsychologischen
Testbatterie Vienna-long (NTBV-long) verglichen. Dabei
wurde die Reliable Change-Index-Methodik
verwendet. Insgesamt gab es kognitive Ver?nderungen bei
einzelnen Patienten, aber die Ver?nderung war sehr
heterogen, mit Gewinnen und Verlusten. Weitere
Untersuchungen sind erforderlich, um die Mechanismen
zu identifizieren, die in einzelnen F?llen zur
Verbesserung oder Verschlechterung kognitiver Funktionen
Schl?sselw?rter Parkinson Krankheit ? Tiefe
Hirnstimulation ? Kognition ? Nucleus subthalamicus
Deep brain stimulation (DBS) is an established
therapy for advanced Parkinson?s disease (PD). The
procedure alleviates tremor, rigidity, bradykinesia and
levodopa-induced dyskinesia. The effectiveness of
bilateral DBS of the subthalamic nucleus (STN) on
motor symptoms in patients with advanced PD is
accepted. While STN-DBS can significantly improve
motor symptoms in PD patients, adverse cognitive effects
have also been reported [
]. The specific effects of
STN-DBS on cognitive function and the related
mechanisms remain unclear.
An early meta-analysis dealing with the cognitive
squeal of STN-DBS in PD revealed significant, albeit
small, declines in executive functions, verbal
learning and memory. Moderate declines were only
reported in semantic and phonemic verbal fluency [
A more recent meta-analysis concluded that a
progressive decrease in verbal fluency after STN-DBS is
consistently reported and, although executive
function is unchanged in the intermediate stage
postoperatively, it tends to decline in the early and later stages
]. Another recent meta-analysis investigating
cognition after deep brain stimulation in PD found small
declines in psychomotor speed, memory attention,
executive functions and overall cognition and
moderate declines were found in both semantic and
phonemic fluency [
]. A recent focused review confirmed
the worsening of verbal fluency after DBS [
most recent meta-analysis suggested that STN-DBS
results in decreased global cognition, memory,
verbal fluency and executive function compared to a PD
control group. No significant difference was found in
other cognitive domains. STN-DBS seems relatively
safe with respect to cognitive function, and future
studies should focus on the exact mechanisms of
possible verbal deterioration after surgery [
Every meta-analysis included studies that were
repeated measure designs that used neuropsychological
tests as dependent variables, many of which are
susceptible to measurement artefacts. The reports
discussed the problem of the influence of practice effects
and regression to the mean effects in repeated
testing designs and suggested that the impact of practice
effects should be assessed and future studies could
be enhanced by assessing un-operated best medically
treated (BMT) patients, clinical control groups and
normal controls at similar time intervals and
statistically controlling for typical practice effects [
The gold standard to evaluate cognitive outcome
are randomized controlled studies. However,
randomized controlled study methodology is not suitable for
assessing cognitive outcome in single patients in the
clinical setting. In order to predict cognitive outcome
in single patients, the reliable change index (RCI)
methodology has been developed [
]. RCI is used
to examine the influence of disease progression over
time and assesses performance across time
accounting for changes due to factors not related to
cognitive impairments. Changes of outcome results due to
practice effects have to be differentiated from changes
due to disease effects or intervention effects. In serial
testing procedures improvement in test performance
can be achieved solely through practice effects. On
the other hand, effects of disease progression and
aging may influence test outcome. Furthermore,
effects of therapeutic interventions must be
considered. Because of the neurodegenerative nature of PD,
progressive changes in neuropsychological testing in
individual cases over time have to be expected.
Recent studies have investigated the effect of DBS
on cognition using RCI methodology. In general,
significant cognitive deterioration was found only
in a few PD-DBS patients suggesting that
neuropsychological evaluations may identify possible mild
cognitive changes following surgery [
As discussed above, an open question is the
influence of practice effects and regression to the mean
effects in repeated testing designs in DBS surgery of PD
patients. Using un-operated medically best treated PD
controls, clinical control groups and normal controls
with similar test-retest intervals offers the opportunity
to investigate practice effects of DBS surgery on
cognitive changes above that of PD progression and
clinical intervention effects. In a recent study our group
showed by using the Neuropsychological Test Battery
Vienna short version (NTBV-short) that roughly 10%
of DBS patients showed cognitive decline 12 months
after the first examination, mainly affecting the
domains attention and executive functioning
(phonemic fluency) using reliable change index
]. However, in our prior study only
cognitive domains and not specific tests were used and as
the NTBV-short uses only a limited number of
neuropsychological tests a more extensive
neuropsychological test battery covering a greater range of
functions would be desirable. Therefore, the goal of the
present study was to investigate cognitive change in
single patients after DBS in PD in relation to PD-BMT
controls, MCI patients and healthy controls using
single variables of the NTBV long and reliable change
Patients and methods
The current data are part of a larger research project,
the Vienna Mild Cognitive Impairment and
Cognitive Decline in Parkinson?s Disease Study
(VMCI-CDPD Study). The VMCI-CD-PD Study is a
prospective cohort study including consecutive,
communitydwelling PD patients who attend the movement
disorder clinic for assessment of their Parkinsonism. The
study protocol was in accordance with the Helsinki
Declaration and approved by the Ethical Committee
of the Medical University of Vienna.
All PD patients underwent clinical examination and
neuropsychological testing. The clinical assessment
encompassed a complete medical history, a detailed
history of PD, which was obtained using a
standardized interview, and a complete neurological
examination including the motor section of the Unified
Parkinson?s Disease Rating Scale (UPDRS-III) [
the modified Hoehn and Yahr scale [
examination and neuropsychological testing were
performed during the ?on-state?. Neuropsychological
baseline testing was performed before DBS surgery,
and as a consequence, before starting stimulation.
Patients who had never undergone computed
tomography (CT) or magnetic resonance imaging (MRI)
during the course of PD and patients showing clinical
features incompatible with previous imaging results
were referred to structural imaging. Both
neuroimaging and clinical features were used to determine
significant cerebrovascular disease or other
co-morbid conditions with a potential impact on cognitive
Inclusion and exclusion criteria were similar to
those used in other studies. All PD patients had to
fulfill UK Parkinson?s Disease Society Brain Bank
] for probable PD. Inclusion and exclusion
criteria were specified as follows. PD-DBS patients
were suffering from PD for at least 5 years with a
positive response to L-DOPA or Apomorphin treatment.
All PD-DBS patients showed not manageable
motor symptoms like dyskinesia, tremor or fluctuations.
Excluded were patients with a secondary
Parkinson syndrome or other degenerative processes with
Parkinson like symptoms. Severe cognitive
impairments like dementia or psychiatric disorders were
exclusion criteria. Psychiatric diagnoses were based
on psychiatric diagnostic interviews performed by
a psychiatrist. Exclusion criteria were not
re-examined before second testing. Any comorbidities and
structural brain lesions that would interfere with the
surgical procedure were ruled out. Controls and
patients were excluded from the study if any of the
following conditions applied: (a) evidence of having
had a stroke as determined by neuroradiologic and
clinical examination, (b) history of severe head injury,
(c) current psychiatric diagnosis according to ICD-10
with the exception of patients with (sub)depressive
symptoms, (d) any medical condition that can lead
to cognitive deterioration including renal, respiratory,
cardiac and hepatic disease, or (e) a diagnosis of
dementia according to DSM IV [
]. Patients were
assessed on their regular medication and were required
to have a Mini-Mental State Examination (MMSE) [
score of ?26. There were no study withdrawals and
participants were enrolled consecutively.
For the assessment of neurocognitive functioning
all participants were subjected the long version of
the Neuropsychological Test Battery Vienna (NTBV)
(meduniwien.ac.at/kpfg). The NTBV assesses
several cognitive domains including attention, executive
functioning, language and memory domains with
corresponding z-scores for single neuropsychological
]. A total z-score across all measurers
is also available [
]. The Alters-Konzentrations-Test
], the number-symbol-test, the Trail Making
Test B (TMT-B) [
] and the symbol counting task
from the cerebral insufficiency test (C. I.)  were
used to assess attention. Executive functions were
investigated using the Trail Making Test A (TMT-A)
], the Maze Test from the NAI Test Battery [
the interference test from the C. I. [
colorword-test from the NAI Test Battery [
] and the
]. Naming as many words as possible
beginning with the letters f, b and l within one minute
for each task was used to tap lexical verbal fluency
]. In order to test language functions, a verbal
fluency task, naming as many animals, groceries and
tools as possible within one minute per task [
a confrontation naming task, the Boston Naming Test
], were used. Episodic memory was tested using
the Verbal Selective Reminding Test (VSRT) with the
subtests of immediate recall, total recall, delayed
recall and recognition [
]. After the completion of the
evaluation, the cognitive status was determined
according to age and education corrected norms using
a normative sample of cognitively healthy controls.
For this purpose, the flexible GAMLSS (Generalized
Additive Models for Location, Scale and Shape) model
class was used [
]. The NTBV was performed two
times. The second testing was performed one year
after the first.
The study included seventy-seven participants
subdivided into four groups. Patients with PD were
divided into a PD-DBS group and a PD-BMT group (best
medical treatment only). The DBS group underwent
deep brain stimulation after the first testing. Patients
received bilateral MR-based, stereotactic DBS surgery.
The optimum electrode position within the STN was
assessed intraoperative at the awake patient, applying
macrostimulation to test for motor improvement and
side effects. In addition, postoperative MR imaging
was used to exclude peri-operative structural
abnormalities and to reassure the correct electrode
positions. Starting with standard DBS parameters (60
microseconds impulse duration at 130 Hz), the voltage
was gradually increased and stimulation parameters
individually adjusted. In parallel, dopaminergic
therapy was gradually decreased, as far as tolerated by the
Community-dwelling patients complaining of
cognitive problems who came to the memory outpatient
clinic for assessment of a possible cognitive disorder
were included in the study. MCI was defined
according to the Petersen criteria [
The healthy control group consisted of participants
without PD and cognitive impairments. Great care
was taken enrolling a sufficient number of cognitively
healthy control subjects living independently at home.
Control subjects were recruited by means of
advertisements. They underwent a screening evaluation using
a standardized clinical interview and cognitive
screening. Imaging procedures, neurological examination,
standard laboratory blood tests and informant reports
were not included in the evaluation. They were
assessed as being in good health. Criteria for healthy
function were identified as being similar to those in
the Mayo research studies [
]: (a) no active
neurological or psychiatric disease, (b) no psychotropic
medications, and (c) the subjects may have medical
disorders but neither they nor their treatment
compromises cognitive function. Cognitive status was given
special attention and cognitively healthy control
subjects were screened for intact cognition. They were
required to have an MMSE [
] score greater than or
equal to 27 and a MOCA [
] score greater than or
equal to 26 adjusted for education. Control subjects
did not overtly complain about cognitive problems.
All four patient groups were similar in terms of age,
gender, Mini-Mental State Examination (MMSE)
], verbal intelligence (WST) [
] and depressive
symptoms (BDI-II) [
]. Using Kruskal-Wallis
analyses no statistical group differences were found (all
p?s > 0.3). Demographic and clinical data are shown in
The difference of (X2 ? X1) characterizes the
individual test scores of a participant at the two test sessions
over time. M2 and M1 represent the mean scores of
the group the patient is compared to. The calculation
of the critical difference (SED) uses the standard
deviation and test-retest reliability of the specific
comparison group. The standard deviation is taken from
the first test session. The retest-reliability coefficient
of a given test is calculated by using test scores of the
first test session (X1) and test scores of the second test
This formula is based on [
] and a significant
change can be assumed at a change of ?1.64 (p = 0.05).
Based on this, the confidence interval is calculated
to determine a minimum and a maximum limit that
represent significant change.
In order to ensure replicability for future studies the
calculations are shown using a case example. A
patient taken from the PD-DBS group is compared to the
PD-BMT group for verbal memory delayed recall. All
scores have already been transformed into z-scores.
The calculation process is divided into two steps. At
first, calculation of the confidence interval using mean
score and standard deviation of the PD-BMT group
are calculated for both test sessions. Mean score of
the verbal memory delayed recall at first testing
session was 0.05 with a standard deviation of 0.82 for the
PD-BMT group. Mean score of the verbal memory
delayed recall at second testing session was ?0.36 with
a standard deviation of 1.35 for the PD-BMT group.
rtt test-retest reliability, SEM standard error of measurement, SED standard error of difference
The test-retest reliability coefficient (rtt = 0.71) results
from the correlation of the test scores across time for
the PD-BMT group. The formula for the standard
error of measurement (SEM) is derived by including the
test-retest correlation coefficient and standard
deviation from the PD-BMT group.
SE M = 0.82 ?
Based on the standard error of measurement the
standard error of difference (SED) is calculated.
The upper and lower scores of the confidence
interval are serving as limiting values for defining
statistical significance. After subtracting the second and the
first mean score (M2 ? M1) the confidence interval is
added or subtracted. Difference of mean scores (DM):
M2 ? M1 = ?0.36 ? 0.05 = ?0.41; Limiting value
deterioration: DM ? CI = ?0.41 ? 1.02 = ?1.43; Limiting value
improvement: DM + CI = ?0.41 + 1.02 = 0.61. A patient?s
RCI has to be higher or lower than the limiting values
in order to detect a statistically significant change
between the first and second testing. The scores of
reliability coefficient, standard error of measurement
and standard error of a difference are calculated like
shown above. Thus, for the verbal memory delayed
recall the figures are as follows: rtt = 0.7; SEM = 0.44;
SED = 0.62; M1 = 0.05; M2 = ?0.36. Limiting value
deterioration: ?1.43; Limiting value improvement: 0.61.
The patient chosen for the illustrative example
reached a z-score of ?0.9 (X1) in the first and ?1.2 (X2)
in the second testing of verbal memory delayed recall.
The mean scores of the group and the individual test
scores are put in the formula for calculating the
reliable change index: RCI = (((?1.2) ? (?0.9)) ? ((?0.482) ?
(?0.075))) * 0.62 = 0.066. This results in a RCI score
of 0.07 for this patient. This value is compared with
the limiting values calculated above. The limiting
values of 0.61 and ?1.43 are not surpassed or undercut.
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Therefore, no significant change of memory ability
in this patient in comparison to the Parkinson BMT
group has been detected.
In order to determine the individual performance
using RCI methodology, RCI calculations were
performed for each participant in each group for every
cognitive measure. The scores of the reliability
coefficient, standard error of measurement, standard error
of difference and the limiting values for improvement
and deterioration as calculated for the PD-BMT group,
healthy control group and MCI group are shown in
Table 2, 3 and 4, respectively. Table 5 shows the results
for the RCI analysis comparing the PD-DBS group to
the calculated limiting values of the PD-BMT group,
the control group and the MCI group, respectively.
The comparison of the PD-DBS group to the
PDBMT group indicated deterioration for the cognitive
measure of Planning Maze Test?NAI time with 31% of
patients showing a significant deterioration. However,
improvements have also been found such as that 31%
of patients had improved Planning Maze Test?NAI
time performance, 18.7% of patients had improved in
TMTB ? TMTA difference score; 18.7% of patients
improved in Phonematic Verbal Fluency PWT total words
and 18.7% of patients improved in verbal memory
delayed recall. No changes were found for the NTBV
total score. The results of the comparison are displayed
in Table 5.
When comparing PD-DBS patients to MCI patients
a similar heterogeneous picture emerged. For Stroop
color words-difference (18.7%), Nonverbal Fluency
Five Point Test?total correct (18.7%) significant
deteriorations have been detected. On the other side,
a larger number of patients improved with 24.8% in
TMTB ? TMTA difference score, 37.2% in verbal
memory delayed recall, 25.0% in Planning Maze Test ?
NAI time. No changes were found for the NTBV total
score. The results of the comparison are displayed in
The comparison of the PD-DBS group with the
healthy control group revealed similar heterogeneous
results compared to the other groups. For the Trail
Making Test ? TMTA (12.5%) significant deteriorations
have been detected. As with the other comparisons,
18.7% of patients improved in verbal memory
delayed recall, with little improvements in other tests.
No changes were found for the NTBV total score. The
results of the comparison are displayed in Table 5.
In order to investigate cognitive changes in patients
with PD with DBS we compared the
neuropsychological profile of four groups, PD patients with DBS,
PD patients best medically treated, MCI patients and
healthy controls at two time points with
re-examination twelve months later. In terms of comparing the
PD-DBS group to the three remaining groups at the
two test sessions a reliable change index was
calculated for every cognitive measure.
Whereas no significant changes for the NTBV
total score were found, there was cognitive change in
specific tests in individual patients, but the change
was very heterogeneous with gains and losses. When
comparing the two Parkinson groups it was
interesting to find a decline regarding specific executive
functions, such as planning, in single patients in the
PDDBS group. However, in a third of the PD-DBS
patients improvements have been found in planning
capability and a fifth of PD-DBS patients phonematic
verbal fluency and verbal memory delayed recall
improved. In all other cognitive measures most patients
experienced no change. The finding of a relatively
large degree of individual variation corroborates
earlier reports using RCI methodology in PD-DBS
The most recent meta-analysis suggested that
STNDBS results in decreased memory, verbal fluency, and
executive function compared to a PD control group.
No significant differences were found in other
cognitive domains, and thus supporting our results
regarding cognitive deterioration [
]. However, according to
our results, many PD patients do also improve after
STN-DBS. The reason why some patients show
decline and others show gains in cognition after
STNDBS is not clear and should be the target of future
research. One could think of effects of preoperative
clinical, cognitive or affective status, pre- and
postoperative medication, postoperative stimulation procedure,
postoperative differences in motivation for
neurocognitive testing and different anatomical location of the
electrodes. Based on our results and the results of
other RCI studies there appears to be heterogeneity in
the prevalence of worsening and gaining effects after
DBS in PD. What is consistently reported as a
groupeffect seems to be mainly driven by a small, but
substantial, subgroup of DBS-treated patients [
One important goal of the present study was to
compare neurocognitive outcome of PD-DBS with
other groups than PD patients using single tests
because up to date no such study has been performed
yet. The only study providing such a comparison used
neurocognitive domains but no single tests [
an investigation is important in order to understand
practice effects in samples other than PD. The
analyses of the neurocognitive outcome in single tests
of the PD-DBS patients compared to the MCI group
and the healthy control group revealed an outcome
pattern that is very similar to the comparison of the
PD-BMT group. Compared to MCI group and healthy
control group PD-DBS patients showed similar gains
and losses in cognition postoperatively. These
results indicate that the influence of practice effects
and regression to the mean effects in repeated testing
designs in DBS surgery in PD patients was
ble in best treated, un-operated PD patients, clinical
control groups and normal controls at similar time
intervals. Thus, practice effects after DBS surgery in
terms of cognitive changes are similar when using
PD-BMT group, MCI group or healthy control group.
These results indicate further that the effect of DBS
is not beyond that one would expect, taking aging
processes into consideration.
One limitation of the present study was the small
sample size. Only seventy-seven participants met
the inclusion criteria, which meant a small-sample
number in each group. However, groups were similar
for age, gender, cognitive status, verbal intelligence
and depressive symptoms. Furthermore, levodopa
equivalent dosage (LED), psychiatric medication (e.g
antidepressants) and medication intake was not
assessed before second testing. Moreover, RCI analysis
does not account for the baseline differences between
patients, warranting some caution when
interpreting these findings. Additionally, no power analysis
concerning the sample size was performed.
In summary, the present study investigated
cognitive outcome in single tests one year after DBS
compared to medically best treated PD patients, MCI
patients and healthy controls using comprehensive
neuropsychological testing. By comparing the reliable
cognitive changes in individual cases over one year we
obtained information regarding cognitive changes due
to deep brain stimulation procedure. PD-DBS patients
showed cognitive gains and losses indicating
heterogeneous outcome after DBS for single patients when
compared to PD-BMT patients. The cognitive
outcome pattern was also comparable when using a MCI
control group or a healthy control group. The reasons
for the specific individual outcome are not yet clear
and should be investigated in future studies.
Acknowledgements We would like to thank Patrick
Wiesbauer for proofreading the paper.
Funding Open access funding provided by Medical
University of Vienna.
Conflict of interest T. Foki, D. Hitzl, W. Pirker, K. Novak,
G. Pusswald, and J. Lehrner declare that they have no
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1. Hickey P , Stacy M. Deep brain stimulation: a paradigm shifting approach to treat parkinson's disease . Front Neurosci . 2016 ; https://doi.org/10.3389/fnins. 2016 . 00173 .
2. Parsons TD , Rogers SA , Braaten AJ , Woods SP , Troster AI . Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinson's disease: a meta-analysis . Lancet Neurol . 2006 ; 5 ( 7 ): 578 - 88 .
3. Wu B , Han L , Sun BM , Hu XW , Wang XP . Influence of deep brain stimulation of the subthalamic nucleus on cognitive function in patients withParkinson's disease . Neurosci Bull . 2014 ; 30 ( 1 ): 153 - 61 .
4. Combs HL , Folley BS , Berry DTR , Segerstrom SC , Han DY , Anderson-Mooney AJ , et al. Cognition and depression following deep brain stimulation of the subthalamic nucleus and globus pallidus pars internus in Parkinson's disease: a meta-analysis . Neuropsychol Rev . 2015 ; 25 ( 4 ): 439 - 54 .
5. Hojlund A , Petersen MV , Sridharan KS , Ostergaard K. Worsening of verbal fluency after deep brain stimulation in Parkinson's disease: a focused review . Comput Struct Biotechnol J . 2017 ; 15 : 68 - 74 .
6. Xie Y , Meng XY , Xiao JS , Zhang J , Zhang JJ . Cognitive changes following bilateral deep brain stimulation of subthalamic nucleus in Parkinson's disease: a meta-analysis . Biomed Res Intern . 2016 ; 17 : 25 - 31 .
7. CheluneGJ,NaugleRI,L?dersH,SedlakJ,AwadI. Individual change after epilepsy surgery: practice effects and baserate information . Neuropsychology . 1993 ; 7 : 41 - 52 .
8. York MK , Dulay M , Macias A , Levin HS , Grossman R , Simpson R , et al. Cognitive declines following bilateral subthalamic nucleus deep brain stimulation for the treatment of Parkinson's disease . J Neurol Neurosurg Psychiat . 2008 ; 79 ( 7 ): 789 - 95 .
9. Schoenberg MR , Duff K , Mold J , Scott JG . Evaluating change in Parkinson's disease following STN DBS: development of reliable change indices for the RBANS . Arch Clin Neuropsychol . 2008 ; 23 ( 6 ): 695 - 6 .
10. ZahodneLB, Okun MS , FooteKD, FernandezHH, Rodriguez RL , Kirsch-Darrow L , et al. Cognitive declines one year after unilateral deep brain stimulation surgery in parkinson's disease: A controlled study using reliable change . Clin Neuropsychol . 2009 ; 23 ( 3 ): 385 - 405 .
11. Higginson CI , Wheelock VL , Levine D , King DS , Pappas CTE , Sigvardt KA . The clinical significance of neuropsychological changes following bilateral subthalamicnucleus deep brain stimulation for Parkinson's disease . J Clin Exp Neuropsychol . 2009 ; 31 ( 1 ): 65 - 72 .
12. Mikos A , Zahodne L , Okun MS , Foote K , Bowers D. Cognitive declines after unilateral deep brain stimulation surgery in parkinson's disease: a controlled study using reliable change, part II . Clin Neuropsychol . 2010 ; 24 ( 2 ): 235 - 45 .
13. Rinehardt E , Duff K , Schoenberg M , Mattingly M , Bharucha K , ScottJ . Cognitivechangeontherepeatablebatteryofneuropsychological status (RBANS) in parkinson's disease with and without bilateral subthalamic nucleus deep brain stimulation surgery . Clin Neuropsychol . 2010 ; 24 ( 8 ): 1339 - 54 .
14. Williams AE , Arzola GM , Strutt AM , Simpson R , Jankovic J , York MK . Cognitive outcome and reliable change indices two years following bilateral subthalamic nucleus deep brain stimulation . Parkinsonism Relat Disord . 2011 ; 17 ( 5 ): 321 - 7 .
15. Schoenberg MR , Rinehardt E , Duff K , Mattingly M , Bharucha KJ , Scott JG . Assessing reliable change using the repeatable battery for the assessment of neuropsychological status (RBANS) for patients with Parkinson's disease undergoing deep brain stimulation (DBS) surgery . Clin Neuropsychol . 2012 ; 26 ( 2 ): 255 - 70 .
16. Foki T , Hitzl D , Pirker W , Novak K , Pusswald G , Auff E , et al. Assessment of individual cognitive changes after deep brain stimulation surgery in Parkinson's disease using the Neuropsychological Test Battery Vienna short version (vol 129 , 2017 ). Wien Klin Wochenschr . 2017 ; 129 ( 15 -16): 585 - 7 .
17. MovementDisorder Society TaskForceOn Rating ScalesFor Parkinson'sDisease. TheUnifiedParkinson'sDiseaseRating Scale ( UPDRS): status and recommendations . Mov Disord . 2003 ; 18 ( 7 ): 738 - 50 .
18. Hoehn MM , Yahr MD . Parkinsonism: onset, progression and mortality . Neurol . 1967 ; 17 ( 5 ): 427 - 42 .
19. Gibb WRL . The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease . J Neurol Neurosurg Psychiatr . 1988 ; 51 : 745 - 52 .
20. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV): American Psychiatric Association; 1993 .
21. Folstein M , Folstein S , MCHugh PR . Mini-mental state: a practical method for grading the cognitive state of patients for the clinician . J Psychiatr Res . 1975 ; 12 : 189 - 98 .
22. Pusswald G , Moser D , Gleiss A , Janzek-Hawlat S , Auff E , Dal-Bianco P , et al. Prevalence of mild cognitive impairment subtypes in patients attending a memory outpatient clinic-comparison of two modes of mild cognitive impairment classification. Results of the Vienna Conversion to Dementia Study . Alz Dement . 2013 ; 9 ( 4 ): 366 - 76 .
23. Gatterer G . Alters-Konzentrations-Test (AKT) . G?ttingen: Hogrefe; 1990 .
24. Tombaugh TN . Trail making test A and B: normative data stratified by age and education . Arch Clin Neuropsychol . 2004 ; 19 ( 2 ): 203 - 14 .
25. Reitan R. Trail Making Test (TMT) . Tucson: Reitan Neuropsychology Laboratory; 1979 .
26. Lehrl S , Fischer B . Kurztest f?r cerebrale Insuffizient (c .I.- Test). Ebersberg: Vless; 1997 .
27. Oswald WD , Fleischmann UM . Das N?rnberger-AltersInventar (NAI) . 3rd ed. G?ttingen, Bern, Toronto, Seattle: Hogrefe; 1995 .
28. Regard M , Strauss E , Knapp P . Children's production on verbal and non-verbal fluency tasks . Percept Mot Skills . 1982 ; 55 ( 3 Pt 1 ): 839 - 44 .
29. Goodglass H , Kaplan P. The assessment of the aphasia and related disorders . 2nd ed. Philadelphia: Lea & Fabinger; 1983 .
30. Morris JC , Heyman A , Mohs RC , Hughes JP , van Belle G , Fillenbaum G , et al. The consortium to establish a registry for alzheimer's disease (CERAD). Part I. clinical and neuropsychological assessment of alzheimer's disease . Neurology . 1989 ; 39 ( 9 ): 1159 - 65 .
31. Lehrner JG , Glei? A , Maly J , Auff E , Dal-Bianco P. Der Verbale Selektive Reminding Test (VSRT) Ein Verfahren zur ?berpr?fung verbaler Ged?chtnisfunktionen . Neuropsychiatrie . 2006 ; 20 ( 3 ): 204 - 14 .
32. Deuschl G , Schade-Brittinger C , Krack P , Volkmann J , Schafer H , Botzel K , et al. A randomized trial of deepbrain stimulation for Parkinson's disease . N Eng J Med . 2006 ; 355 ( 9 ): 896 - 908 .
33. Diener HCPN , Berlit P , et al. Leitlinien f?r Diagnostik und Therapie in der Neurologie . Stuttgart: Thieme; 2003 .
34. Petersen RC , Smith GE , Waring SC , Ivnik RJ , Tangalos EG , Kokmen E. Mild cognitive impairment: clinical characterization and outcome . Arch Neurol . 1999 ; 56 ( 3 ): 303 - 8 .
35. Ivnik R. Mayo 's older Americans normative studies: WAISR, WMS-R and AVLT norms for ages 56 through 97 . Clin Neuropsychol . 1992 ; 6 : 1 - 104 .
36. Nasreddine ZS , Phillips NA , B?dirian V , Charbonneau S , Whitehead V , Collin I , et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment . J Am Geriatr Soc . 2005 ; 53 : 695 - 9 .
37. Schmidt K-HM P. Wortschatztest (WST). Weinheim : Beltz; 1992 .
38. Hautzinger M , Bailer M , Worall H , Keller F. Beck Depressions-Inventar (BDI). Testhandbuch . Bern: Huber; 1995 .