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SREE CHITRA TIRUNAL INSTITUTE FOR MEDICAL SCIENCES AND TECHNOLOGY
THIRUVANANTHAPURAM, KERALA
VALIDATION OF MALAYALAM VERSION OF MONTREAL COGNITIVE ASSESSMENT FOR KERALITE PATIENTS WITH PARKINSON’S DISEASE Thesis submitted in partial fulfilment of the rules and regulations
for DM degree Examination
By
Dr. Radhamani M Resident in Neurology
Month and year of submission: May 2015
DEPARTMENT OF NEUROLOGY Jan 2012 – May 2015
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DECLARATION
I, Dr. RADHAMANI M., hereby declare that this project was
undertaken by me under the supervision of the faculty, Department of
Neurology, Sree Chitra Tirunal Institute for Medical Sciences and
Technology.
Thiruvananthapuram Dr.RADHAMANI M. Date: 01-05-2015 DM Neurology resident
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Forwarded
The candidate, Dr. RADHAMANI M. has carried out the project under
my guidance.
Thiruvananthapuram Dr.SYAM K.
Date: 01-05-2015 Associate Professor
Department of Neurology
SCTIMST
Thiruvananthapuram
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Forwarded
The candidate Dr. RADHAMANI M., has carried out the minimum
required project.
Thiruvananthapuram PROF. Dr. MURALIDHARAN NAIR Date: 01-05-2015 Prof & HOD Department of Neurology
SCTIMST Thiruvananthapuram
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ACKNOWLEDGEMENT
I take this opportunity to express my sincere gratitude to Dr. Syam K, Associate
Professor of Neurology and Movement Disorders expert, SCTIMST, my guide for the study,
for his expert guidance, constant review, kind help and keen interest at each and every step
during the completion of the study.
I am indebted to Dr. Asha Kishore, Professor of Neurology and Movement
Disorders expert,SCTIMST for her guidance, encouragement and support during the period
of the study.
I thank Dr. Muralidharan Nair, Professor and Head, Department of Neurology for
his guidance, encouragement and valuable suggestions during the period of the study.
I am thankful to Ms. Sunitha J., Neuropsychologist ,department of Neurology,
SCTIMST, for her valuable input and assistance to the study.
I am indebted to Dr.Ramshekhar Menon, Assistant Professor, Department of
Neurology, for his guidance and support during the period of the study.
I express my sincere thanks to Dr. Sankara Sarma, Professor, Achutha Menon
Centre for Health Science Studies, for helping me with the statistical analysis of this study.
I express my heartfelt gratitude to Mr. Gangadhara Sarma, clinical psychologist
and social worker, Comprehensive Centre for Movement Diosrders, SCTIMST, for the
assistance in translation and for his sincere efforts and constant assistance during the entire
course of the study.
I extend my gratitude to all my patients who participated in this study.
Dr Radhamani M
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INDEX
1 Introduction 1
2 Review of literature 4
3 Objectives 30
4 Materials and Methods of the study 31
5 Statistical Analysis 36
6 Results 37
7 Discussion 51
8 Conclusion 55
9 Bibliography 57
10 Annexure 71
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INTRODUCTION
Parkinson’s disease (PD), the second most common
neurodegenerative disorder was initially known as a ‘motor” disorder
characterized by tremor, bradykinesia, rigidity and postural abnormalities. It
is now known that nonmotor manifestations are very common in PD, and
contribute to disability and impaired quality of life in patients.1,2 ,3,4
Cognitive impairment is one among the important non-motor manifestations
of PD . Non-motor manifestations, including cognitive dysfunction
dominate the clinical picture in the later stages of the disease. 1,2 Cognitive
dysfunction is an important non-motor manifestation, 5,6 with significant
impacts on functioning, quality of life and caregiver burden.7,8,9,10 The
spectrum of cognitive dysfunction range from mild cognitive impairment
(PD-MCI) to PD dementia (PDD). Cognitive dysfunction increases the risk
of nursing home placement and contribute to personal and socioeconomic
burden in patients with Parkinson’s disease 11,12 PD-MCI is common and
appears to place patients at risk of progressing to dementia.13 Dementia
occurs upto 83% of patients with PD over 20 years. 14 Even mild cognitive
deficits in PD are associated with functional impairment15,16 and worse
QOL.17,18
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Early identification is very important to start early interventions to
improve functioning and quality of life . Brief and sensitive
neuropsychological tests are required to administer in these patients for
early identification of the cognitive decline . Cognitive domains affected in
PD are attention , working memory, executive function, language, memory
and visuospatial function. 5,6,13 Validated neuropsychological tests sensitive
for detection of cognitive dysfunction in these domains are available in
English and other languages . Tests requiring long time are difficult to use
in PD patients in the clinic . Many short neuropsychological tests have
been developed and validated in PD patients . The Montreal Cognitive
Assessment was designed by by Nasreddine et al.19 as a brief screening
tool for MCI and has become an increasingly popular screening tool for
cognitive dysfunction not only in PD but also in the setting of Alzheimer
disease,stroke,vascular dementia, traumatic brain injury, and frontotemporal
dementia . This screening tool tests Short-term memory , visuospatial
function, executive function , attention ,concentration and working memory,
language and orientation in 10 minutes time. 19
The usefulness of MoCA as a suitable, accurate, and brief test for
screening all levels of cognition in PD has also been established. 20 In the
present study, we aimed to create a cross cultural adaptation of MoCA
(MoCA- Malayalam - “MoCA-M”) , and test its metric properties and
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reliability for use in Malayalam-speaking patients with PD. We hope that
MoCA-M will be a novel screening tool useful for detecting cognitive
impairment in its early stage itself, for use in Keralite population.
Review of Literature
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REVIEW OF LITERATURE
Parkinson’s disease is the second most common neurodegenerative
disorder with increased prevalence in males and age more than 60 years and
is a common cause of disability. PD was initially described by Dr James
Parkinson in “An essay of the shaking palsy”.21 The description of the
disorder was similar to how we describe it today, as a progressive disease
due to probable degenerative pathology in the central nervous system. The
main symptoms were characterized by resting tremor, flexed posture and
shuffling gait. The intellect and senses were described as being intact in the
initial description; cognitive dysfunction not considered as part of disease
till 1960s. There have been many diagnostic criteria proposed for the
clinical diagnosis; the United Kingdom Parkinson’s Disease Society Brain
Bank (UKPDSBB) criteria22 is the most widely used one and is well
validated.
Review of Literature
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UK PARKINSON’S DISEASE SOCIETY BRAIN BANK CLINICAL
DIAGNOSTIC CRITERIA
1. Diagnosis of Parkinsonian Syndrome
Bradykinesia
At least one of the following
1. Muscular rigidity
2. 4-6 Hz rest tremor
3. postural instability not caused by primary visual, vestibular,
cerebellar, or proprioceptive dysfunction
2. Exclusion criteria for Parkinson’s disease
• History of repeated strokes with stepwise progression of
parkinsonian features
• History of repeated head injury
• History of definite encephalitis
• Oculogyric crises
• Neuroleptic treatment at onset of symptoms
• More than one affected relative
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• Sustained remission
• Strictly unilateral features after 3 years
• Supranuclear gaze palsy
• Cerebellar signs
• Early severe autonomic involvement
• Early severe dementia with disturbances of memory, language, and
praxis
• Babinski sign
• Presence of cerebral tumor or communication hydrocephalus on
imaging study
• Negative response to large doses of levodopa in absence of
malabsorption
MPTP exposure
3. Supportive prospective positive criteria for Parkinson’s disease
Three or more required for diagnosis of definite Parkinson’s disease
in combination with step one
• Unilateral onset
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• Rest tremor present
• Progressive disorder
• Persistent asymmetry affecting side of onset most
• Excellent response (70-100%) to levodopa
• Severe levodopa-induced chorea
• Levodopa response for 5 years or more
• Clinical course of ten years or more
Prevalence of PD
The prevalence of PD in people over 65 years of age is around 1-2%
and increases from 0.6% in the ages 65-69 to 2.8% in the ages 85-
89years.23,24 The cumulative incidence ( the life time risk) of PD up to 89
years of age is close to 3%.24 The mean age at symptom onset is in the late
60’s and population based studies report age at diagnosis to around 70 years
of age.25
Non motor symptoms of PD
PD is classically considered as a motor disorder but a diverse range
of nonmotor symptoms (NMS) including cognitive dysfunction occur in the
majority and dominate the clinical picture in the later stages of the
Review of Literature
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disease.1,2 The nonmotor symptoms(NMS) of PD are increasingly
recognized as being critical to identify and treat because of their impact on
quality of life in PD perhaps having an even greater impact than motor
symptoms.4,26 The most commonly described primary NMS of PD are
autonomic dysfunction, cognitive abnormalities, sleep disorders, mood
disorders, pain, and sensory disorders.27 Non-motor symptoms in PD
include neuropsychiatric symptoms with depression, apathy, hallucinations,
cognitive impairment and dementia, sleep disorders with restless legs,
REMsleep behavior disorder, excessive daytime somnolence, vivid
dreaming and insomnia, autonomic symptoms with bladder disturbances,
orthostatic hypotension and sweating, sensory symptoms with olfactory
disturbance, pain and visual dysfunction and gastrointestinal symptoms with
constipation.4,27 There are also NMS in PD that are secondary to
treatment, such as impulse control disorders and psychosis. 27 Recent studies
shows that NMS may be present in the early PD 28 or may be the presenting
symptom in some patients. 29 NMS are missed in 50% of patients with PD
in routine consultations.28
Cognitive dysfunction in PD
Patients with PD have an almost six fold increased risk of
developing dementia compared with age-matched individuals
without PD.30 Cognitive dysfunction in PD may present in varying degrees.
Review of Literature
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Occurrence is common even among patients with mild motor symptoms,
and includes difficulties such as bradyphrenia, or slowing of thinking, and
executive dysfunction, such as impairment of planning and goal-directed
behaviors.27 Subtle cognitive impairment is common in early disease and
one study has reported that over a third of patients have deficits at the time
of their diagnosis.31 Cognitive dysfunction is an important non-motor
manifestation,5,6 with significant impacts on functioning, quality of life and
caregiver burden.7,8,9,10
Although the cognitive deficits in PD have traditionally been
classified as being ‘‘subcortical’’ in nature, a range of cognitive domains
are impaired in PD patients without dementia. The spectrum of cognitive
dysfunction range from mild cognitive impairment (PD-MCI) to PD
dementia (PDD). Cognitive dysfunction in PD not only increases the risk of
nursing home placement, but also contribute to a more malignant course of
illness, and exacerbate personal and socioeconomic burden.11,12 PD-MCI is
common and appears to place patients at risk of progression to dementia;
13even mild cognitive deficits in PD are associated with functional
impairment 14,15 and worse QOL.17,18
Review of Literature
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Pathogenesis of cognitive decline in PD
PD is characterized by a progressive widespread diffusion of the Lewy
body neuropathology from subcortical to cortical structures, therefore at
different disease stages, PD patients present different loads of Lewy body
neuropathology and different involvements of subcortical and cortical
structures.32 PD is associated with cortical Lewy pathology including limbic
and neocortical regions33 and AD related changes, including the
hippocampus suggesting that both PD and AD pathologies contribute to
cognitive decline in PD.34 Lewy bodies and neuronal loss in the substantia
nigra occurs concurrently with accumulation of α-synuclein deposition in
cholinergic neurons of the BF. 32 Loss of midbrain dopaminergic neurons of
the substantia nigra pars compacta, results in striatal dopaminergic
denervation.32 Cholinergic projection losses that vary from 5% to 25% in
PD subjects both with and without dementia.35,36
Pathogenesis of cognitive dysfunction in PD is heterogeneous and
may differ between individuals and between subtypes. Clinicopathological
studies showed brainstem predominant LB disease in majority and less
frequent brainstem-limbic forms(33%) and neocortical type of LB disease
in PD-MCI.37 Multiple pathogenic substrates in PDD include dysfunctions
of the subcortico-cortical networks 38,39 resulting from neuronal loss and
atrophy in amygdala and limbic areas,40 cholinergic deficits in cortex 41,42
Review of Literature
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and thalamus associated with neuronal loss in the nucleus basalis of
Meynert (NBM) and decreased nicotinic acetylcholine receptors.43,44 The
number of LBs in the frontal cortex or of LB densities in the limbic cortex
may be a better predictor of dementia in PD.45
Cognitive deficits in early PD are associated with impaired
nigrostriatal dopaminergic function, which results in abnormal processing in
the frontostriatal circuit with reduced prefrontal and parietal metabolism.46
Parkinson’s disease -mild cognitive impairment (PD-MCI )
PD-MCI is thought to be common in non-demented PD patients and
is associated with increasing age, disease duration and disease severity.
PD-MCI is thought to predict the development of PD-D.13,47 The concept of
PD-MCI is now well supported by a number of studies showing an
association between electrophysiological, imaging, biochemical and
neuropathological variables and cognitive impairment in PD patients
without dementia.48-58. The QEEG measures of background rhythm
frequency and relative power in the theta band are potential predictive
biomarkers for dementia incidence in PD and EEG measures have potential
use as biomarkers in the study of both early and late cognitive deterioration
in PD.48 SPECT studies done in PD patients with normal cognition had
limited areas of hypometabolism in the frontal and occipital cortices and in
Review of Literature
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the PDMCI patients, there were extensive areas of hypometabolism in the
posterior cortical regions, including the temporo-parieto-occipital junction,
medial parietal, and inferior temporal cortices suggest that posterior cortical
dysfunction is the primary neuroimaging feature of PD patients at risk for
dementia.50,51
In noncomplicated PD, structural neuroimaging (cranial computed
tomography and MRI) may be normal or show mild diffuse brain atrophy
and temporal lobe changes in early PD . Hippocampal atrophy and lateral
ventricular enlargement are structural biomarkers for PD-MCI . Marked
gray matter atrophy occurs in PDD, whereas far fewer extensive changes are
evident in PD-MCI.52 Studies on cerebrospinal fluid (CSF) biomarkers
suggest that CSF Aβ-42, and tau predict cognitive decline in PD. 55,56
Prevalence of PD-MCI
The studies done so far indicate that 18.9% -38.2 % of non-demented
PD patients have PD-MCI.47,59-65. In nondemented PD patients mean
prevalence was 27%; range, 19%–38% and is associated with the
subsequent development of PD Dementia(PDD) .The frequency of MCI
increases with age and with duration and severity of PD.13 Studies on newly
diagnosed PD patients also have shown significant cognitive decline over
Review of Literature
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years.66,67 Nonamnestic, single-domain impairment (i.e., any single
nonmemory domain) is the most common subtype of PD-MCI.13
Figure1.Flowchart for the diagnosis of mild cognitive impairment and its
subtypes
Review of Literature
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Risk factors for PD-MCI
Different studies showed that increasing age, male gender, lower
levels of education,later onset of disease, greater PD severity and longer
disease duration are associated with PD-MCI.68,69
Patterns of cognitive deficit in PD-MCI
Cognitive domains typically affected in PD include executive
function, attention, processing speed, visuospatial, learning and memory.68
PD-MCI may affect a range of cognitive domains, but single domain
impairment is more common than multiple domains and within a single
domain, nonamnestic impairment is more common than isolated amnestic
deficits. 13 In the nonamnestic single domain , high proportion of
visuospatial and executive function deficits observed such as problem
solving and working memory. Attentional-executive dysfunction is common
in most PD patients without dementia and up to half of these may also
experience visuospatial and free recall memory problems.68
Definition of PD MCI
PD MCI denotes cognitive decline that is not normal for age but with
essentially normal functional activities (fail to meet the criteria for PD-D)
and could be present even at the time of diagnosis of PD and prior to
Review of Literature
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initiation of dopaminergic therapy. This operational definition was
uniformly followed in the longitudinal 47,54 and cross-sectional 56-61 studies
done so far, but there was no uniformity in the number of impaired
cognitive tests required in each domain, the number of involved domains
and the degree of involvement in each domain, to be classified as PD-MCI .
The need for formal diagnostic criteria for PD-MCI has been highlighted13
and the Movement disorder Society (MDS) commissioned a task force to
review the available literature on PD-MCI and formulate a diagnostic
criteria. The MDS task force diagnostic criteria have been published
recently.70 The MDS Task Force diagnostic criteria include (1)
characterization of the clinical syndrome and (2) methods for its diagnosis.
PD-MCI Criteria
The diagnosis of PDMCI needs satisfaction of the inclusion and
exclusion criteria specified; two levels of diagnostic categories and various
subtypes of PD-MCI have been defined. PD-MCI is a syndrome defined by
clinical, cognitive,and functional criteria.70 The MDS Task Force criteria
are rooted in the MCI criteria previously described, but modified to address
issues relatively specific to PD. The criteria were also designed to be
consistent with the MDS proposed PDD criteria and thereby allow
transitions between categories of normal cognition, MCI, and dementia.71
Review of Literature
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I. Inclusion criteria
1. Diagnosis of Parkinson’s disease as based on the UK PD Brain Bank
Criteria17
2. Gradual decline, in the context of established PD, in cognitive ability
reported by either the patient or informant, or observed by the
clinician
3. Cognitive deficits on either formal neuropsychological testing or a
scale of global cognitive abilities (detailed in section III)
4. Cognitive deficits are not sufficient to interfere significantly with
functional independence, although subtle difficulties on complex
functional tasks may be present.
II. Exclusion criteria
1. Diagnosis of PD dementia based on MDS Task Force proposed
criteria57
2. Other primary explanations for cognitive impairment (e.g.,
delirium,stroke, major depression, metabolic abnormalities, adverse
effects of medication,or head trauma)
Review of Literature
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3. Other PD-associated comorbid conditions (e.g., motor impairment or
severe anxiety, depression, excessive daytime sleepiness, or
psychosis)that, in the opinion of the clinician, significantly influence
cognitive testing
III. Specific guidelines for PD-MCI level I and level II
categories
A . Level I (abbreviated assessment)
1. Impairment on a scale of global cognitive abilities validated for use in
PD or
2. Impairment on at least two tests, when a limited battery of
neuropsychological tests is performed (i.e., the battery includes less
than two tests within each of the five cognitive domains, or less than
five cognitive domains are assessed)
[scales of global cognitive abilities validated in PD are –MoCA,
SCOPA-COG(Scales for Outcomes of Parkinson’s disease–Cognition) ,
PD-CRS(Parkinson’s Disease-Cognitive Rating scale), MDRS(Mattis
Dementia Rating Scale)]
Review of Literature
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B. Level II (comprehensive assessment)
1. Neuropsychological testing that includes two tests within each of the
five cognitive domains (i.e., attention and working memory, executive,
language, memory, and visuospatial)
2. Impairment on at least two neuropsychological tests, represented by
either two impaired tests in one cognitive domain or one impaired
test in two different cognitive domains
3. Impairment on neuropsychological tests may be demonstrated by:
Performance approximately 1 to 2 SDs below appropriate
norms or
Significant decline demonstrated on serial cognitive testing or
Significant decline from estimated premorbid levels
IV. Subtype classification for PD-MCI (optional, requires two
tests for each of the five cognitive domains assessed and is
strongly suggested for research purposes) a
a Subtype classifications are applicable only to those PD-MCI who have had at least two
tests within each of the five cognitive domains administered.
Review of Literature
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1. PD-MCI single-domain—abnormalities on two tests within a single
cognitive domain (specify the domain), with other domains
unimpaired or
2. PD-MCI multiple-domain—abnormalities on at least one test in two
or more cognitive domains (specify the domains)
Neuropsychological tests for the five cognitive domains
Attention and working memory
WAIS-IV (or earlier version) Letter Number Sequencing,
WAIS-IV Coding (or earlier version) or other substitution task,
written or oral
Trail Making Test,
Digit span backward or digit ordering,
Stroop color-word test.
Executive function
Wisconsin Card Sorting Test (CST), or modified CST(Nelson’s
modification)
Tower of London test–Drexel version, or Stockings of Cambridge
(CANTAB)
Review of Literature
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Verbal fluency test, such as letter fluency (COWAT or similar tests),
Category fluency (animals, supermarket, or similar), or alternating
fluency tasks(if a well-standardized version is used).
10 points Clock Drawing Test
Language
WAIS-IV (or earlier version) Similarities
Confrontation naming task, such as Boston Naming Test (or short-
form validated in PD) or Graded Naming Test
Memory
Word list learning test with delayed recall and recognition conditions,
such as Rey’s Auditory Verbal Learning Test, California Verbal
Learning Test, Hopkins Verbal Learning Test, and Selective
Reminding Test
Prose recall test with a delayed recall condition, such as Wechsler
Memory Scale-IV Logical Memory subtest (or earlier version) or
River mead Behavioural Memory Test, paragraph recall subtest
Brief Visuospatial Memory Test–Revised (BVMT-R)
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Visuospatial function
Benton’s Judgment of Line Orientation
Hooper Visual Organization Test
Clock copying (e.g., Royall’s CLOX)
The level I category allows for the diagnosis of PDMCI based on an
abbreviated cognitive assessment, because comprehensive testing may not
always be practical or available. Level I criteria provide less diagnostic
certainty than level II . When a limited battery of neuropsychological tests is
performed, impairment must be present on at least two tests to diagnose PD-
MCI by level I criteria. Level I criteria do not allow complete sub typing of
PD-MCI.
For the diagnosis of PD-MCI by level II criteria and PD-MCI sub
typing, the task force recommends formal, comprehensive
neuropsychological testing that includes at least two tests for each of the
five cognitive domains previously listed. Impairment should be present on at
least two tests, either within a single cognitive domain or across different
cognitive domains.
Review of Literature
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Risk of progression to PDD
Mild cognitive impairment in Parkinson's disease is an important
predictor for the progression to PDD. Longitudinal studies on non-
demented PD patients show that 20-60% develop PD dementia over 2-5
years.54,72-77 Information on the conversion of PD-MCI to PDD is
scanty.47,54,59 Around 60% of PDMCI are converted to PD-D over 4 years,
compared to 20% of PD patients with normal cognition.47 Cognitive decline
correlating with the neuropathologic stage of PD demonstrated in a
clinicopathological study also support PDMCI as a risk factor for PD-D.78,79
It has been shown that majority of PD patients develop dementia over
time.80,81 The cumulative prevalence of PDD for patients surviving more
than 10 years is at least 75%.80,81 The point prevalence of PD-MCI13,72 and
PD-D6 are similar. Thus, PDMCI precedes PDD and majority of PD-MCI
are converted to PDD over time.13
PDD
Diagnosis of PD dementia must be based on the presence of deficits
in at least two of the four core cognitive domains (attention, memory,
executive and visuo-spatial functions) as shown in clinical and cognitive
examination, and be severe enough to affect normal functioning. The
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Movement Disorder Society (MDS) Task Force defined the clinical
diagnostic criteria for PD-D.71
Features of dementia associated with Parkinson’s disease
I. Core features
1. Diagnosis of Parkinson’s disease according to Queen Square Brain
Bank criteria.
2. A dementia syndrome with insidious onset and slow progression,
developing within the context of established Parkinson’s disease and
diagnosed by history, clinical, and mental examination , defined as :
Impairment in more than one cognitive domain
Representing a decline from premorbid level
Deficits severe enough to impair daily life (social, occupational, or
personal care), independent of the impairment ascribable to motor
or autonomic symptoms.
II. Associated clinical features
1. Cognitive features
• Attention: Impaired. Impairment in spontaneous and focused
attention, poor performance in attentional tasks; performance may
fluctuate during the day and from day to day.
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• Executive functions: Impaired. Impairment in tasks requiring
initiation, planning, concept formation, rule finding, set shifting or set
maintenance; impaired mental speed (bradyphrenia)
• Visuo-spatial functions: Impaired. Impairment in tasks requiring
visual-spatial orientation, perception, or construction
• Memory: Impaired. Impairment in free recall of recent events or in
tasks requiring learning new material, memory usually improves with
cueing, recognition is usually better than free recall
• Language: Core functions largely preserved. Word finding difficulties
and impaired comprehension of complex sentences may be present
2. Behavioral features:
• Apathy: decreased spontaneity; loss of motivation, interest, and
effortful behavior
• Changes in personality and mood including depressive features and
anxiety
• Hallucinations: mostly visual, usually complex, formed visions of
people, animals or objects
• Delusions: usually paranoid, such as infidelity, or phantom boarder
(unwelcome guests living in the home) delusions
• Excessive daytime sleepiness
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Based on these features clinical diagnostic criteria for probable and
possible PD-D are described .
Scientific and clinical significance of identifying PD-MCI
As discussed above, PD-MCI is common and precede PD-D. Most
PD patients develop dementia,80-83 the impact of which is substantial. PD-D
has major consequences for psychiatric morbidity,84 functioning,15,85,86
caregiver burden,87,88 nursing home placement9 and mortality.89,90 . Even
mild cognitive deficits affect functioning and quality of life in PD.15-18 Early
identification is very important and help early interventions to improve
functioning and QOL as well as drug development and other measures
aimed to delay the development of PDD. This has got public health
importance, considering the commonness of PD.91 Early recognition of
cognitive impairment could offer a window for novel therapeutic
interventions, aiming to alter the course of this natural history.
Tools for Assessment of Cognition in PD
There are a number of issues that are not fully resolved in the
cognitive testing in PD, including the ideal cut-off scores, number of tests to
be done in each domain, number of tests/domains to be involved to classify
as PD-MCI, the potential non-linear nature of cognitive decline in PD, and
the issue of whether different cognitive domains decline at same or different
Review of Literature
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rates.13 Assessment of cognition in PD can be complicated by disease- or
medication-related effects, such as bradykinesia, fatigue, sleepiness, and
mood disorders, which can adversely affect test results regardless of
cognitive abilities.13 The recently published MDS PD-MCI diagnostic
criteria70 specifies two levels of diagnosis; level I is the “abbreviated
assessment” and level II, “Comprehensive assessment”.
Level I requires impairment on a scale of global cognitive abilities
validated for use in PD or impairment on a limited battery of
neuropsychological tests . Level II requires testing with at least two
cognitive tests, assessing each of the five cognitive domains (Attention and
working memory, executive function, language, memory and visuospatial
function). As each of the recommended tests take 5-15 minutes13 a
minimum of 1- 1 ½ hours may be required for the individual patient. This
has practical challenges; hence the level I testing may be more suitable in
the clinic settings and require only impairment in a scale of global cognitive
abilities validated for use in PD or a limited battery of cognitive tests.
Neuropsychological Scales for Assessing Global Cognitive Abilities
validated for use in PD are Montreal Cognitive Assessment (MoCA);
Parkinson’s Disease-Cognitive Rating scale (PD-CRS); Scales for
Outcomes of Parkinson’s disease–Cognition(SCOPA-COG) and Mattis
Dementia Rating Scale(MDRS) . Based on the Movement disorder Task
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Force’s evaluation criteria the Montreal Cognitive Assessment (MoCA),
appeared to be the most suitable measure and recommended consideration
of the MoCA as a minimum cognitive screening measure in clinical trials of
PD.13,70
The Montreal Cognitive Assessment (MoCA)
The MoCA was designed by by Nasreddine et al.19 in English
language as a brief screening tool for MCI and has become an increasingly
popular screening tool for identifying cognitive impairment . As it is brief
(can be administered in around 10 minutes)13 and can be easily administered
even by non-specialist staff it has become very useful and common
screening test. MoCA covers a range of executive functions and addresses
frontal functions better than the widely used Mini-Mental Status
Examination (MMSE).92 The MoCA is divided into 7 subscores :
visuospatial/executive(5 points); naming (3 points); memory(5points for
delayed recall); attention (6 points);language (3 points); abstraction (2
points); and orientation (6 points). One point is added if the subject has < 12
years of education.19 MoCA has high sensitivity and specificity for MCI and
has good test-retest reliability, internal consistency and content validity 92. It
has been studied in patients with MCI , Alzheimers disease (AD), Vascular
Cognitive Impairment, post stroke ,PD, Huntington’s disease , Epilepsy
,traumatic brain injury, Frontotemporal dementia,multiple sclerosis and
Review of Literature
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tumors of brain and found to be a useful screening tool in all these
conditions. 93,94
The usefulness of MoCA as a suitable, accurate and brief test for
screening all levels of cognition in PD, has been demonstrated.20,95 MoCA
doesn’t have the pronounced ceiling effect seen with MMSE and is a more
sensitive tool to identify early cognitive impairment in PD, especially PD-
MCI.20,96It has also been found that approximately half of the patients with
normal MMSE have cognitive impairment based on MoCA.97 Based on
these findings, the MDS task force has recommended MoCA as a
neuropsychological scale to test the global cognitive abilities in PD,13,70 to
make a “level I” diagnosis of PD-MCI. The optimal MoCA screening cut-
off values for PD-D and PD- MCI have recently been defined as 21/30
and 26/30 respectively.95 The scale was originally designed in English and
cross-cultural adaptation and validation was done for use in 43 other
languages.93
Addenbrooke’s Cognitive Examination
The Addenbrooke’s Cognitive Examination (ACE),a global cognition
screening battery, is a reliable and sensitive tool consists of six components
evaluating separate cognitive domains.98 A maximum score of 100 is
weighted as orientation(10) , attention(8) , memory(35) , verbal fluency(14)
Review of Literature
36
, language(28) , and visuospatial ability(5) . Scores for each of the six
domains can be calculated separately and their sum gives the composite
score on the ACE. The MMSE score can also be calculated from this . The
ACE can be administered in 15 to 20 minutes.98 Addenbrookes Cognitive
Examination is validated for dementia evaluation in PD, with a cut-off
score of 83 points.99 It is adapted into Malayalam and validated for use
in our population and normative data for different ages and educational
levels are available.100,101
Mini Mental Status Examination
The Mini Mental Status Examination (MMSE) (Folstein et al., 1975),
is a widely used cognition screening test in many parts of the world ,
modified and adapted into many local languages. Malayalam version of
MMSE with normative scores are published earlier.101 MMSE is being used
for long time for testing cognition in PD . But it is less sensitive for the
detection of cognitive impairment seen in early PD.96 It shows a ceiling
effect in patients and normal controls.97 Studies in patients with PD showed
that approximately half of patients with a normal MMSE score have
cognitive impairment by testing with MoCA.97
Aims & Objectives
37
Aims and objectives of the study
1. Cross-cultural adaptation of Montreal Cognitive assessment (MoCA)
scale into the regional language (Malayalam)
2. Study the validity and reliability of Montreal Cognitive assessment-
Malayalam (MoCA-M) for cognitive assessment in Parkinson’s
disease patients .
Materials and Methods
38
Materials and Methods of the study
Cross-cultural adaptation of MoCA to Malayalam (MoCA-M)
MoCA is copyright protected cognitive assessment tool required
written permission of the copyright holder for translation and use for
research purpose. We contacted the copyright holder and obtained
permission for translation (to Malayalam) and use for this project. The
copyright holders have also provided guidelines for translation of MoCA to
Malayalam. The English version was used as a base for translation. The 5-
word recall and sentence repetition items was adapted to the language and
culture, based on the guidelines provided. In order to ensure accurate
translation of the test and instructions, a back translation (from Malayalam
to English) was done and compared with the original English version. The
translation and back-translation was done independently by two bilingual
experts, who are clinical psychologists well versed with similar tasks and
consensus was obtained. The final version was discussed and approved
within an internal committee consisting of the bilingual experts as well as
the investigators.
Materials and Methods
39
Validation of Montreal Cognitive assessment-Malayalam
(MoCA-M)
Study design and setting
The study was a hospital based cross-sectional study. The subjects
were selected from among the patients attending the movement disorder
clinic of our tertiary care University hospital (Sree Chitra Tirunal Institute
for Medical Sciences and Technology, Thiruvananthapuram).
Study period:
The study was conducted over a period of 18 months from January
2013 to June 2014.
Methods
For validation, the test (MoCA-M) was administered to 100
consecutive patients with Parkinson’s disease, attending the Movement
Disorders clinic of SCTIMST and satisfying the entry criteria, and 100
normal controls. The controls were selected from the hospital staff, friends
and relatives of hospital staff and visitors of the in-patients in the hospital
who agreed to participate.
Materials and Methods
40
Ethical considerations:
Written informed consent was obtained from all the subjects
participating in the study. The study was approved by the Institutional
Ethics Committee. (SCT/IEC/438/DECEMBER-2012)
Inclusion criteria (for PD patients):
1. Diagnosis of PD, as per standard diagnostic criteria (United Kingdom
Parkinson’s Disease Society Brain Bank Diagnostic Criteria)22
2. Ability to read, understand and write Malayalam well.
3. Ability to provide written informed consent.
Inclusion criteria (for Controls)
1. No known neurological disorders.
2. Normal neurologic examination (except for assessment of higher
functions)
3. Age, gender and level of education matched with patients.
4. Ability to read, understand and write Malayalam well.
5. Ability to provide written informed consent.
Materials and Methods
41
Exclusion criteria (for PD patients and Controls)
1. Clinically significant depression (Beck’s Depression Inventory
(BDI) Score ≥20) 102
2. Any significant neurological, psychiatric or medical co-morbidity
interfering with cognitive testing or affecting cognitive functions in
the judgement of the investigators.
The Malayalam version of MoCA(MoCA-M) was applied to
consecutive patients with PD diagnosed using the United Kingdom
Parkinson’s Disease Society Brain Bank Diagnostic Criteria , attending the
Movement Disorders clinic of our hospital having atleast 10 years of formal
education and able to read , write and understand Malayalam. MoCA-M was
also applied to age and education -matched healthy controls without any
neurological disorders . All the patients underwent a formal neurological
examination including assessment using Unified Parkinson’s Disease rating
Scale (UPDRS I-IV)103 The UPDRS part III (motor examination) was done
in the “off” state in patients having motor fluctuations. The severity of
motor symptoms of PD was assessed by the Hoehn and Yahr stage. The age
of onset of motor symptoms of PD, duration of motor symptoms and details
of ongoing treatment was collected by directly interviewing the patients /
Materials and Methods
42
caregivers and by review of hospital files. The controls also underwent a
neurological examination to ensure that they have no neurological disorders.
The neuropsychologic evaluation was done in the “On” (well
medicated) state with the help of the qualified Neuropsychologist, attached
to the Movement Disorders Program of the Institute. All the subjects (PD
patients and controls) were undergone neuropsychological assessment using
the MoCA-M, Addenbrooke’s Cognitive Examination –Malayalam (ACE-
M)100 , and Beck depression inventory(BDI) . Those with clinically
significant depression (Beck’s Depression Inventory score >20)102 or any
significant neurological, psychiatric, or medical co-morbidity affecting
cognitive functions or interfering with cognitive testing in the judgment of
the investigators were excluded.
The ACE has several advantages (The MMSE is also included in it, is
validated for use in Parkinson’s disease,98 adaptation is available for use in
Malayalam speaking population100 and cut-off scores are well defined in our
population, adjusted for age and level of education.101 The normative data
for each of the individual domains of ACE also has been published101
making it ideal as a standard for validating the new scale. The Malayalam
version of ACE (M-ACE)100 was used for the study. A subgroup of subjects
were re-examined using the MoCA-M after an interval of 2 weeks to
determine the test-retest reliability.
Statistical Analysis
43
Statistical analysis
Cronbach’s alpha was calculated to assess the internal
consistency of MoCA-M. Pearson correlation coefficient was used to the
assess test-retest reliability as well as to assess the relationship between
MoCA-M scores and the performance in other cognitive tests. The data were
analyzed using statistics software (Statistical Package for the Social
Sciences (SPSS) Inc, Illinois, Chicago) with guidance from the Medical
Statistics expert of the institute.
Results
44
Results
Baseline clinical characteristics
There were 100 patients with PD and 100 healthy controls. Mean age
of patient group was 57.8(± 9.3) years ,range 35-78 years . In the control
group mean age was 58.94(±8.42),range 39-85 years .
The mean years of education was 12.19(±3.46) in patient group, and
13.6(±3.20)in the control group .
Table 1 Demographic data of patients and controls
Patient Control P value
Age (years) 57.8(± 9.3) 58.94(±8.42) 0.38
Education (years) 12.19(±3.46) 12.2 (±1.97) 0.98
Age and education were similar in the patient and control groups and
there was no statistically significant difference .
In the patient group 71% were men and 29% were women and in the control
group 53% were men and 47% were women.
Results
45
Figure 2. Sex distribution
The mean duration of motor symptoms was 6.58 (±4.04) years ,
range from 2-18 years. The mean age of onset of symptoms was
52.42(±10.02) years range from 30-76 years . The mean Levodopa
equivalent dose (LEDD) was 615(±295.51)mg .
The severity of motor symptoms according to Hoehn and Yahr (H
and Y) stage was as follows: Stage 1- 7% (7patients), stage2−44%
(44patients), stage 3−43% (43patients), stage 4−6% (6 patients). Majority
of the patients were in stages 2 and 3.
0%
20%
40%
60%
80%
100%
Patients Controls
71
53
29
47
male female
Results
46
Figure 3 Number of patients distributed in various H&Y stages
7
44 43
6
00
5
10
15
20
25
30
35
40
45
50
H&Ystage
1 2 3 4 5
Results
47
Neuropsychology Test Results:
Patients
The mean MoCA score was 24.41( ±4.04) ranging from 8-30 in
patients with PD. ACE mean score was 83.99(±9.99)ranging from 49-99 .
MMSE mean score was 28.55±1.73 ranging from 21-30 .
Controls
The mean MoCA score was 27.78±1.67ranging from 23-30 in
normal controls. ACE mean score was 91.56±4.98 ranging from 80-99 .
MMSE mean score was 29.220±0.98 ranging from 23-30 .
Table 2.Mean scores in cognitive testing in patients
No of
patients
Minimum
score
Maximum
score
Mean
score
Std dev
MoCA 100 8 30 24.4 4.04
ACE 100 49 99 83.99 9.99
MMSE 100 21 30 28.55 1.73
Results
48
Table 3. Mean scores in cognitive testing in patients
No of
controls
Minimum
score
Maximum
score
Mean
score
Std dev
MoCA 100 23 30 27.78 1.67
ACE 100 80 99 91.56 4.98
MMSE 100 23 30 29.22 0.98
The mean MoCA-M, MMSE, and ACE scores of the patients and
healthy controls are shown in Table 4. The scores in all the three tests
differed significantly between patients and normal controls .
Table 4. The MoCA-M, MMSE, and ACE scores of patients and healthy
controls
Patients Healthy controls P value
MoCA-M 24.41 ±4.04 27.78±1.67 <0.001
MMSE 28.55±1.73 29.220±0.98 0.003
ACE 83.99±9.99 91.56±4.98 <0.001
Results
49
Mean BDI score was 3.9(±4.84) , range from 0-20 in the patient
group . In the control group mean score was 3(±4.5) ranging from 4-12 .
There was no significant difference between patient and control group.
Table 5. BDI scores of patients and controls
Mean Std dev Range
Patient 3.9 4.84 4-20
Control 3 4.4 0-12
There was no correlation between age and the scoring in cognitive
tests , in the patient group (pearson correlation R 0 .023 and p value 0.82) or
in the control group (R -.04 and p value 0.69) .
Table 6. Correlation of age and MoCA scores
Correlations
MoCA_TOTAL
Age (years) patient
Pearson Correlation .023
Sig. (2-tailed) .823
N 100
Age (years) control
Pearson Correlation -.040
Sig. (2-tailed) .690
N 100
Results
50
There was no significant difference in scores between males and
females in the patient group (p value 0.83) or the control group(p value
0.873).
Table 7. MoCA score in male and female in control group
GENDER Mean N Std. Deviation Median Minimum Maximum
male 27.76 53 1.55 28.00 25.0 30.0
female 27.81 47 1.81 28.00 23.0 30.0
Total 27.78 100 1.67 28.00 23.0 30.0
Table 8. MoCA score in male and female in patient group
GENDER Mean N Std. Deviation Median Minimum Maximum
male 24.47 71 3.57 26.00 14.0 30.0
female 24.28 29 5.07 26.00 8.0 29.0
Total 24.41 100 4.04 26.00 8.0 30.0
There was no correlation between duration of PD and the scoring in
cognitive testing in MoCA , R was .057 and p value is 0.57 . There was no
correlation between age onset of symptoms and scoring in cognitive testing
R -.012 and p value was .91. There was no correlation between LEDD and
MoCA scores , R -.053 p value was 0.60
Results
51
Table 9. Correlation of MoCA score with demographics of patients
Correlations
MoCA total
Duration in years
Pearson Correlation .057
Sig. (2-tailed) .574
N 100
Age of onset years
Pearson Correlation -.012
Sig. (2-tailed) .909
N 100
Daily L-dopa dose
Pearson Correlation -.012
Sig. (2-tailed) .904
N 100
LEDD
Pearson Correlation .053
Sig. (2-tailed) .601
N 100
The mean MoCA score in H&Y stage 1 was 23.71±7.36 , stage 2 was
24.34±3.65, stage3 was 24.28±3.95 and stage 4 was 26.67±2.34 . There was
no significant difference in the MoCA score in different H&Y stages and
the p value was 0.51 .
Results
52
Table 10. MoCA score in various H&Y stages in the off state of patients
H&Y stage off N Mean Std.
Deviation Median Minimum Maximum
1.0 7 23.71 7.36 27.00 8.0 29.0
2.0 44 24.34 3.65 26.00 14.0 28.0
3.0 43 24.28 3.95 26.00 14.0 30.0
4.0 6 26.67 2.34 26.50 24.0 30.0
Total 100 24.41 4.04 26.00 8.0 30.0
There was no correlation between H&Y stage of PD and the scoring
of cognitive testing in MoCA , MMSE or ACE .
Figure 4.Scoring in cognitive tests in each H&Y stages
0
10
20
30
40
50
60
70
80
90
100
1 2 3 4 5
MoCA30
MMSE30
ACE100
Results
53
Table 11. Scores in cognitive tests in each H&Y stage
1 2 3 4 P value
MoCA mean
score 23.71±7.36 24.34±3.65 24.28±3.95 26.67±2.34 0.59
ACE mean score 82.28±16.24 84.51±9.5 82.91±9.64 91.00±5.34 0.39
MMSE mean
score 28±3.10 28.69±1.53 28.40±1.76 29.33±0.81 0.62
Results did not show any significant difference in the test scores in
patients with various H&Y stages . There was no correlation between
H&Y stage and MoCA score .
Results
54
Validity and Reliability of MoCA-M
MoCA-M showed good internal consistency; the Cronbach’s alpha
for MoCA-M was 0.72 in patients with PD and 0.40 in controls.
There was also excellent test-retest reliability for the total score of
MoCA-M, as well as for the individual items.
Table 12. Test‑retest reliability of MoCA-M
Cognitive domains Pearson’s correlation coefficient P value
Visuo spatial/executive 0.87 <0.0001
Naming 0.63 <0.0001
Attention 0.96 <0.0001
Language 0.95 <0.0001
Abstraction 0.96 <0.0001
Delayed recall 0.96 <0.0001
Orientation 0.58 0.001
Total 0.97 <0.0001
The scores of MoCA,MMSE and ACE differed significantly
between patients and normal controls with a significant p value . There was
significant difference in the scores of MoCA-M and ACE between healthy
controls and patients and p value was <0.001. Though the difference in the
MMSE scores of controls and patients was less it was significant
statistically and the p value was 0.003 .
Results
55
Table 13. The MoCA-M, MMSE, and ACE scores of patients and healthy
controls
Patients Healthy controls P value
MoCA-M 24.41 ±4.04 27.78±1.67 <0.001
MMSE 28.55±1.73 29.220±0.98 0.003
ACE 83.99±9.99 91.56±4.98 <0.001
The MoCA-M scores correlated well with the MMSE (R = 0.67; P <
0.0001) and ACE (R=0.81;P<0.0001) scores in patients with PD .
Table 14.Correlation of MoCA scores with MMSE and ACE in patient
group
Correlations
MoCA_TOTAL ACE_TOTAL MMSE
MoCA_TOTAL
Pearson Correlation 1 .807** .670**
Sig. (2-tailed) .000 .000
N 100 100 100
ACE_TOTAL
Pearson Correlation .807** 1 .730**
Sig. (2-tailed) .000 .000
N 100 100 100
MMSE
Pearson Correlation .670** .730** 1
Sig. (2-tailed) .000 .000
N 100 100 100
**. Correlation is significant at the 0.01 level (2-tailed).
Results
56
The healthy controls showed good correlation of MoCA scores with
ACE (R = 0.49; P < 0.0001); however, correlation with MMSE scores (R =
0.23; P = 0.02) was weak.
Table 15. Correlation of MoCA scores with MMSE and ACE in control
group
Correlations
MoCA_TOTAL ACE_TOTAL MMSE
MoCA_TOTAL
Pearson Correlation 1 .489** .233*
P Value .000 .020
N 100 100 100
ACE_TOTAL
Pearson Correlation .489** 1 .229*
P Value .000 .022
N 100 100 100
MMSE
Pearson Correlation .233* .229* 1
P Value .020 .022
N 100 100 100
**. Correlation is significant at the 0.01 level (2-tailed). *. Correlation is significant at the 0.05 level (2-tailed).
Results
57
Table 16. Correlation of MoCA score with ACE and MMSE score of
patients and controls
ACE
patient
ACE
control
MMSE
score
patient
MMSE
score
control
MoCA
score
Pearson
correlation R 0.81 0.49 0.67 0.23
P value <0.0001 <0.0001 <0.0001 0.02
Discussion
58
Discussion
There is increasing evidence that dementia is common in advancing
PD, affecting up to 80% of patients followed long term.14 Recognition of
cognitive impairment at its initial stage will enable clinicians to educate
patients and family members about prognosis and to allow informed
decisions about the risks and benefits of therapeutic interventions. Screening
tests used in PD should be brief and sensitive for the type of cognitive
dysfunction seen in these patients as it is difficult to do long tests due to the
motor dysfunction . MoCA is well-recognized as a suitable sceening test for
cognition in PD94-97 as it is a brief test , has demonstrated good test–retest
and interrater reliabilities and high intraclass correlation coefficients in
patients with PD and has been translated to many languages.93,94 The
cognitive domains tested by MoCA include executive and visuospatial
function, memory, language, and attention. The
domains of executive and visuospatial function are known to be affected
relatively early in PD and hence MoCA could be a useful instrument to
screen for cognitive dysfunction in PD.
In this study we translated and adapted MoCA into our regional
language Malayalam and demonstrated the usefulness of the Malayalam
version of MoCA for screening cognitive functions in PD. We created
Discussion
59
MoCA-M (the test and instructions for testing have been posted at the
official website of MoCA93 and are available on line at www.mocatest.org)
by translating MoCA to Malayalam and cross-culturally adapting the
relevant items. We have changed the 5 words in the delayed recall item
relevant to our language and culture. Back translation of the test and
instructions was done by bilingual experts and compared with the original
English version, and consensus was obtained. The back translations were
accepted by the group who invented the original version of MoCA and hold
the copyright.
The mean duration of motor symptoms of PD in our patient group
was 6.58years . The mean age of patients was 57.8 years which was
comparable with the control group . The mean age of onset of symptoms
was 52.42(±10.02) years . Most of the patients were in the H and Y stage 2
or 3 and there was no patients in the stage 5 .There was no significant
relation between the H&Y stage and scoring in cognitive testing in our
study. Males were more in the patient group which was expected as PD is
more common in males.
The MoCA-M takes about10minutes to administer. MoCA-M was
compared with ACE for several reasons–it is a brief test battery
encompassing all the cognitive domains,98 its validity in PD has been
Discussion
60
demonstrated,99 its validated adaptation for Malayalam speaking population
is available 100 , and it also gives the MMSE score
MoCA-M showed good internal consistency, and the test-retest
reliability was excellent. We found that MoCA-M scores of patients
correlated well with their performance in ACE. The MoCA-M scores also
showed good correlation with MMSE scores in patients with PD. MoCA-M
is more brief and easy to administer compared to ACE . MoCA’s superiority
for testing cognition in PD, compared to MMSE has already been
demonstrated.65,96,97 The cognitive dysfunction in PD is characterized by a
frontal, attentional-executive dysfunction in most patients, in addition to
visuospatial defects and memory problems.66-69 The utility of MoCA for
screening cognition in PD and its superiority over MMSE are well described
96,97 and it tests frontal functions better than MMSE, in addition to testing
the other cognitive domains.
We also examined 100 age and education matched healthy volunteers
and demonstrated good correlation of MoCA-M scores with performance in
ACE. However, unlike the observation in patients with PD, correlation of
MMSE scores with MoCA–M scores of control group was weak. The
MMSE scores were significantly higher for healthy volunteers, and the poor
correlation between MoCA-M and MMSE scores in this group is
Discussion
61
attributable to the ceiling effect of MMSE,65,72 which is not observed for
MoCA.
We found that the performance of patients with PD in all the three
tests was significantly worse compared to controls. The MoCA-M mean
score in the patient group was 24.41(±4.04) versus 27.78(±1.67) in the
control group. The mean MoCA-M score of the patients was falling below
the cut-off levels defined for MCI, for the original version of MoCA19. The
ACE score was 83.99(±9.99) in the patient group and 91.56(±4.99) in the
control group . The significantly low MoCA-M and ACE scores in patients,
compared to controls is not surprising, considering the mean duration of PD
in our patient group; a considerable number of them are expected to have
MCI. MoCA-M is a cross-cultural adaptation of MoCA, its normative data
and cut-off scores for MCI in PD and PD-D need to be separately defined
by further studies .
In this study we have done cross cultural adaptation of MoCA into
Malayalam and demonstrated the reliability and validity of the Malayalam
version for screening cognition in patients with PD .
Conclusion
62
CONCLUSION
1. MoCA –M is a cross cultural adaptation of MoCA for use in
Malayalam speaking patients. MoCA’s validity for screening
cognition for patients with all stages of PD, is already well
established .
2. We showed that the MoCA –M had good test- retest reliability and
internal consistency, similar to the original version of MoCA.
3. The comparison of MoCA-M with other standard cognitive tests
used in patients with PD, showed good correlation .
4. MoCA-M scores differed significantly between patients with PD
and healthy volunteers , paralleling the observation in a more
elaborate and established cognitive testing instrument- the
Malayalam version of ACE.
5. MoCA-M is valid and reliable, similar to the original English
version, for screening for cognitive dysfunction in Malayalam
speaking PD patients.
Summary
63
SUMMARY
We created a cross-cultural adaptation of MoCA (MoCA-M) , for use
for cognitive screening in Malayalam speaking patients, especially with
PD. We have shown that it is a valid and reliable tool for the purpose.
Bibliography
64
Bibliography
1. Shulman LM, Taback RL, Bean J, Weiner WJ. Comorbidity of the nonmotor
symptoms of Parkinson’s disease. Mov Disord 2001; 16:507–510
2. Chaudhuri KR, Healy DG, Schapira AHV. Non-motor symptoms of Parkinson’s
disease: diagnosis and management. Lancet Neurol 2006; 5: 235–45.
3. Syam Krishnan, Do Nonmotor Symptoms in Parkinson’s Disease Differ
fromNormal Aging?; Movement Disorders, Vol. 26, No. 11, 2011
4. Tien K. Khoo, ,The spectrum of nonmotor symptoms in early Parkinson disease;
Neurology 2013;80:276–281
5. Riedel O, Klotsche J, Forstl H, Henn F et al. Cognitive impairment in 873
patients with idiopathic Parkinson’s disease. Results from the German Study on
Epidemiology of Parkinson’s Disease with Dementia (GEPAD). J Neurol 2008;
255:255–264.
6. Aarsland D, Zaccai J, Brayne C. A systematic review of prevalence studies of
dementia in Parkinson’s disease. Mov Disord 2005;20: 1255-63.
7. Global Parkinson’s Disease Survey Steering Committee. Factors impacting on
quality of life in Parkinson’s disease:results from an international survey.Mov
Disord 2002;17:60–67.
8. Schrag A, Jahanshahi M, Quinn N. What contributes to quality of life in patients
with Parkinson’s disease? J Neurol Neurosurg Psychiatry 2000; 69: 308–12.
Bibliography
65
9. Aarsland D, Tandberg E, Laake K. Predictors of nursing home placement in
Parkinson’s disease: a population-based, prospective study. J Am Geriatr Soc
2000; 48: 938–42.
10. Findley L, Aujla M, et al. Direct economic impact of Parkinson’s disease: a
research survey in the United Kingdom. Mov Disord 2003; 18: 1139–45.
11. Huse D, Schulman K, Orsini L, Castelli- Haley J,Kennedy S, Lenhart G
(2005)Burden of illness in Parkinson’s disease. Mov Disord 2005:1449–1454.
12. Klockgether T (2004) Parkinson’s disease: clinical aspects. Cell Tissue Res
318:115–120.
13. Litvan I, Aarsland D, Adler CH, et al. MDS task force on mild cognitive
impairment in Parkinson’s disease: critical review of PDMCI. Mov Disord
2011;26:1814–1824.
14. Mariese A. Hely , The Sydney Multicenter Study of Parkinson’s Disease: The
Inevitability of Dementia at 20 years; Movement DisordersVol. 23, No. 6, 2008,
pp. 837–844 .
15. Rosenthal E, Brennan L, Xie S, et al. Association between cognition and function
in patients with Parkinson disease with and without dementia. Mov Disord.
2010;25:1170–1176.
16. Martin RC, Okonkwo OC, Hill J, et al. Medical decision-making capacity in
cognitively impaired Parkinson’s disease patients without dementia. Mov Disord.
2008;23:1867–1874.
Bibliography
66
17. Klepac N, Trkulja V, Relja M, Babic T. Is quality of life in nondemented
Parkinson’s disease patients related to cognitive performance? A clinic-based
cross-sectional study. Eur J Neurol. 2008;15:128–133.
18. Marras C, McDermott MP, Rochon PA, Tanner CM, Naglie G, Lang AE.
Predictors of deterioration in health-related quality of life in Parkinson’s disease:
results from the DATATOP trial. Mov Disord. 2008;23:653–659.
19. Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive
Assessment, MoCA: a brief screening tool for mild cognitive impairment J Am
Geriatr Soc 2005;53: 695–699.
20. Dalrymple-Alford JC, MacAskill MR, et al. The MoCA: well-suited screen for
cognitive impairment in Parkinson disease. Neurology 2010;75:1717–1725.
21. Parkinson J. An Essay on the Shaking Palsy. London: Sherwood, Neely, and
Jones; 1817:66.
22. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of
idiopathic Parkinson’s disease. A clinico-pathological study of 100 cases. JNNP
1992;55:181-184
23. Pollock M, Hornabrook RW. The prevalence, natural history and dementia of
Parkinson’s disease. Brain 1966, 89:429–448.
24. De Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, et
al. Prevalence of Parkinson’s disease in Europe: A collaborative study of
population-based cohorts. Neurology 2000, 54:21–23. 15
Bibliography
67
25. Linder J, Forsgren L.et al, Incidence of Parkinson’s disease and parkinsonism in
northern Sweden: a population-based study. Mov Disord 2010, 25:341–8.
26. Barone P, Antonini A, Colosimo C, et al. The PRIAMOstudy: a multicenter
assessment of nonmotor symptoms and their impact on quality of life in
Parkinson’s disease. Mov Disord 2009;24:1641–1649.
27. Nonmotor Symptoms in Parkinson’s Disease Expanding the View of Parkinson’s
Disease Beyonda Pure Motor, Pure Dopaminergic ProblemVictor W. Sung,;
Neurol Clin 31 (2013)
28. Aarsland D, Bronnick K, Larsen JP, Tysnes OB, Alves G. Cognitive impairment
in incident, untreated Parkinson disease: the Norwegian ParkWest study.
Neurology 2009;72:1121–1126
29. O’Sullivan SS, Williams DR, Gallagher DA, Massey LA,Silveira-Moriyama L,
Lees AJ. Nonmotor symptoms as presenting complaints in Parkinson’s disease: a
clinicopathological study. Mov Disord 2008;23:101–106.
30. Aarsland D, Andersen K, Larsen JP et al. Risk of dementia in Parkinson’s
disease: a community-based, prospective study. Neurology2001; 56: 730–6.
31. T. Foltynie, C. E. G. Brayne, ,“The cognitive ability of an incident cohort of
Parkinson’s patients in the UK. The CamPaIGN study,” Brain, vol. 127, no.3, pp.
550–560, 2004.
32. Braak, H., de Vos, R. A., E. N., and Braak,E. (2003). Staging of brain
pathology related to sporadic Parkinson’s disease.Neurobiol. Aging 24, 197–211
Bibliography
68
33. Beach TG, Adler CH, Caviness J, Shill HA, Connor DJ, Sabbagh MN,Walker
DG, Arizona Parkinson’s Disease Consortium (2009)Unified staging system for
Lewy body disorders: correlation with nigrostriatal degeneration, cognitive
impairment and motor dysfunction. Acta Neuropathol 117:613–634
34. Kurt A Jellinger, Expert Rev. Neurother. 12(12), 1451–1466 (2012);
Neurobiology of cognitive impairment in Parkinson’s disease
35. Bohnen NI, Kaufer DI, Ivanco LS, et al. Cortical cholinergic function is more
severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo
positron emission tomographic study.Arch Neurol. 2003; 60:1745–1748.
36. Shimada H, Hirano S, Shinotoh H, et al. Mapping of brain acetylcholinesterase
alterations in Lewy body disease by PET. Neurology. 2009; 73:273–278
37. Kurt A. Jellinger, , Mild cognitive impairment in Parkinson disease: heterogenous
mechanisms; J Neural Transm (2013) 120:157–167.
38. Zgaljardic DJ, Borod JC, Foldi NS, Mattis P. A review of the cognitive and
behavioral sequelae of Parkinson's disease: relationship to frontostriatal circuitry.
Cogn Behav Neurol. 2003 ;16(4):193-210.
39. Dirnberger G, Frith CD, Jahanshahi M. Executive dysfunction in Parkinson's
disease is associated with altered pallidal-frontal processing. Neuroimage.
2005;25(2):588-99.
40. Kalaitzakis ME , Pearce RK. The morbid anatomy of dementia in Parkinson’s
disease. ActaNeuropathol.118(5),587–598(2009)
Bibliography
69
41. Bohnen NI, Kaufer DI, Hendrickson R, Ivanco LS, Lopresti BJ, Constantine GM,
Mathis ChA, Davis JG, Moore RY, Dekosky ST. Cognitive correlates of cortical
cholinergic denervation in Parkinson's disease and parkinsonian dementia. J
Neurol. 2006;253(2):242-7.
42. Dubois B, Pilon B, Lhermitte F, Agid Y. Cholinergic deficiency and frontal
dysfunction in Parkinson's disease. Ann Neurol. 1990;28(2):117-21.
43. Martijn L.T.M. Müller, Cholinergic Dysfunction in Parkinson’s Disease, Curr
Neurol Neurosci Rep. 2013 September ; 13(9): 377
44. Mattila PM, Rinne JO, Helenius H, Dickson DW, Röyttä M. Alpha-synuclein-
immunoreactive cortical Lewy bodies are associated with cognitive impairment
in Parkinson's disease. Acta Neuropathol. 2000;100(3):285-90.
45. Irwin DJ, White MT,Toledo JB etal. Neuropathologic substrates of Parkinson
disease dementia.Ann.Neurol.72(4),587–598 (2012).
46. Ekman U, Eriksson J, Forsgren L, Mo SJ,Riklund K, Nyberg L. Functional
brainactivity and presynaptic dopamine uptakein patients with Parkinson’s
disease andmild cognitive impairment: a cross-sectional study. Lancet Neurol.
11(8), 679–687(2012).
47. Janvin CC, Larsen JP, Aarsland D, Hugdahl K. Subtypes of mild cognitive
impairment in Parkinson’s disease: progression to dementia. Mov Disord.
2006;21:1343–1349.
Bibliography
70
48. Caviness JN , Evidente VG, et al. Both early and late cognitive dysfunction
affects the electroencephalogram in Parkinson’s disease. Parkinsonism Relat
Disord. 2007;13:348–354.
49. Onofrij M, Gambi D, Malatesta G, Ferracci F, Fulgente T. Electrophysiological
techniques in the assessment of aging brain: lacunar state and differential
diagnosis. Eur Neurol. 1989;29(Suppl 2):44–47.
50. Huang C, Mattis P, Eidelberg D. Metabolic abnormalities associated with mild
cognitive impairment in Parkinson disease. Neurology. 2008;70: 1470–1477.
51. Hosokai Y, Nishio Y, Hirayama K, et al. Distinct patterns of regional cerebral
glucose metabolism in Parkinson’s disease with and without mild cognitive
impairment. Mov Disord. 2009;24: 854–862.
52. Beyer MK, Janvin CC, Larsen JP, Aarsland D. A magnetic resonance imaging
study of patients with Parkinson’s disease with mild cognitive impairment and
dementia using voxel-based morphometry. J Neurol Neurosurg Psychiatry.
2007;78:254–259.
53. Seto-Salvia N, Clarimon J, Pagonabarraga J, et al. Dementia Risk in Parkinson
Disease: Disentangling the Role of MAPT Haplotypes. Arch Neurol.
2011;68:359–364.
54. Williams-Gray CH, Evans JR, Goris A, et al. The distinct cognitive syndromes of
Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain.
2009;132:2958–2969.
Bibliography
71
55. Alves G, Bronnick K, Aarsland D, et al. CSF amyloid-{beta} and tau proteins,
and cognitive performance, in early and untreated Parkinson’s Disease: the
Norwegian ParkWest study. J Neurol Neurosurg Psychiatry. 2010;81:1080–1086.
56. Siderowf A, Xie SX, Hurtig H, et al. CSF amyloid {beta} 1–42 predicts cognitive
decline in Parkinson disease. Neurology. 2010; 75:1055–1061.
57. Ballard C, Jones EL, Londos E, Minthon L, Francis P, Aarsland D. alpha-
Synuclein antibodies recognize a protein present at lower levels in the CSF of
patients with dementia with Lewy bodies. Int Psychogeriatr. 2010;22:321–327.
58. Adler CH, Caviness JN, Sabbagh MN, et al. Heterogeneous neuropathological
findings in Parkinson’s disease with mild cognitive impairment. Acta
Neuropathol. 2010;120:827–828
59. Williams-Gray CH, Foltynie T, Brayne CE, Robbins TW, Barker RA. Evolution
of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain.
2007;130:1787–1798.
60. Pai MC, Chan SH. Education and cognitive decline in Parkinson’s disease: a
study of 102 patients. ActaNeurol Scand. 2001;103:243–247.
61. Aarsland D, Bronnick K, Tysnes OB, Alves G. Cognitive impairment in
incident, untreated Parkinson disease: the Norwegian ParkWest study.
Neurology. 2009;72:1121–1126.
62. Hoops S, Nazem S, Siderowf AD, et al. Validity of the MoCA and MMSE in the
detection of MCI and dementia in Parkinson disease. Neurology. 2009;73:1738–
1745.
Bibliography
72
63. Foltynie T, Brayne CE, Robbins TW, Barker RA. The cognitive ability of an
incident cohort of Parkinson’s patients in the UK. The CamPaIGN study. Brain.
2004;127:550–560.
64. Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive profile of patients
with newly diagnosed Parkinson disease. Neurology. 2005;65:1239–1245.
65. Mamikonyan E, Moberg PJ, Siderowf A, et al. Mild cognitive impairment is
common in Parkinson’s disease patients with normal Mini-Mental State
Examination (MMSE) scores. Parkinsonism Relat Disord. 2009;15:226–231.
66. Kandiah N, Narasimhalu K, Lau PN, Seah SH, Au WL, Tan LC. Cognitive
decline in early Parkinson’s disease. Mov Disord. 2009; 24:605–608.
67. Muslimovic D, Post B, De Haan RJ, Schmand B. Cognitive decline in
Parkinson’s disease: a prospective longitudinal study. J Int Neuropsychol Soc.
2009;15:426–437.
68. D. Muslimovic, B. Post, J. D. Speelman, and B. Schmand, Cognitive profile of
patients with newly diagnosed Parkinson disease,” Neurology, vol. 65, no. 8, pp.
1239–1245, 2005.
69. D. Verbaan, J. Marinus, M. Visser et al., “Cognitive impairment in Parkinson’s
disease,” Journal of Neurology, Neurosurgery andPsychiatry, vol. 78, no. 11, pp.
1182–1187, 2007.
70. Litvan I, Goldman JG, Tröster AI, Schmand BA, Weintraub D, Petersen RC,
Mollenhauer B, Diagnostic criteria for mild cognitive impairment in Parkinson's
Bibliography
73
disease: Movement Disorder Society Task Force guidelines. Mov Disord. 2012
Mar;27(3):349-56.
71. Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia
associated with Parkinson’s disease. Mov Disord2007;22:1689–1707
72. Aarsland D, Williams-Gray C, et al. Mild cognitive impairment in Parkinson
disease: a multicenter pooled analysis. Neurology. 2010;75:1062–1069.
73. Marder K, Tang MX, Cote L, Stern Y, Mayeux R. The frequency and associated
risk factors for dementia in patients with Parkinson’s disease. Arch Neurol.
1995;52:695–701.
74. Levy G, Schupf N, Tang MX, et al. Combined effect of age and severity on the
risk of dementia in Parkinson’s disease. Ann Neurol. 2002;51:722–729.
75. Aarsland D, Andersen K, Larsen JP, Lolk A, Nielsen H, Kragh-Sorensen P. Risk
of dementia in Parkinson’s disease: a community-based, prospective study.
Neurology. 2001;56:730–736.
76. Stern Y, Marder K, Tang MX, Mayeux R. Antecedent clinical features associated
with dementia in Parkinson’s disease. Neurology. 1993;43:1690–1692.
77. Kandiah N, Narasimhalu K, Lau PN, Seah SH, Au WL, Tan LC. Cognitive
decline in early Parkinson’s disease. Mov Disord. 2009; 24:605–608.
78. Muslimovic D, Post B, Speelman JD, Schmand B. Cognitive decline in
Parkinson’s disease: a prospective longitudinal study. J Int Neuropsychol Soc.
2009;15:426–437.
Bibliography
74
79. Braak H, Rub U, Del Tredici K. Cognitive decline correlates with
neuropathological stage in Parkinson’s disease. J Neurol. Sci. 2006;248:255–258.
80. Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P. Prevalence and
characteristics of dementia in Parkinson disease: an 8-year prospective study.
Arch Neurol. 2003;60:387–392.
81. Hobson P, Meara J ;. ;Mild cognitive impairment in Parkinson's disease and
its progression onto dementia: a 16-year outcome evaluation of the Denbighshire
cohort;Int J Geriatr Psychiatry. 2015 Feb 11.
82. Buter TC, van den Hout A, Matthews FE, Larsen JP, Brayne C, Aarsland D.
Dementia and survival in Parkinson disease: a 12- year population study.
Neurology. 2008;70:1017–1022.
83. Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney
multicenter study of Parkinson’s disease: the inevitability of dementia at 20
years. Mov Disord. 2008;23:837–844.
84. Aarsland D, Bronnick K, Ehrt U, et al. Neuropsychiatric symptoms in patients
with Parkinson’s disease and dementia: frequency, profile and associated care
giver stress. J Neurol Neurosurg Psychiatry. 2007;78:36–42.
85. Uc EY, Rizzo M, Anderson SW, Sparks JD, Rodnitzky RL, Dawson JD. Driving
with distraction in Parkinson disease. Neurology. 2006;67:1774–1780.
86. Bronnick K, Ehrt U, et al. Attentional deficits affect activities of daily living in
dementia-associated with Parkinson’s disease. J Neurol Neurosurg Psychiatry.
2006;77:1136–1142.
Bibliography
75
87. Schrag A, Hovris A, Morley D, Quinn N, Jahanshahi M. Caregiver- burden in
parkinson’s disease is closely associated with psychiatric symptoms, falls, and
disability. Parkinsonism Relat Disord. 2006;12:35–41.
88. Aarsland D, Larsen JP, Karlsen K, Lim NG, Mental symptoms in Parkinson’s
disease are important contributors to caregiver distress. Int J Geriatr Psychiatry.
1999;14:866–874.
89. Lo RY, Tanner CM, Albers KB, et al. Clinical features in early Parkinson disease
and survival. Arch Neurol. 2009;66:1353–1358.
90. Levy G, Tang MX, Louis ED, et al. The association of incident dementia with
mortality in PD. Neurology. 2002;59:1708–1713.
91. Campenhausen S, Bornschein B,Wick R, Botzel K, Sampaio C, Poewe W,Oleson
J,Oertel W, Siebert U, Berger K, Dodel R. Prevalence and incidence of
Parkinson’s disease in Europe. Eur Neuropsychopharm 2005; 15:473–490.
92. Ismail Z, Rajji TK, Shulman KI. Brief cognitive screening instruments: an
update. Int J Geriatr Psychiatry. 2010; 25(2):111-20.
93. www.mocatest.org
94. Julayanont P, Phillips N, Chertkow H, and Nasreddine ZS. The Montreal
Cognitive Assessment (MoCA): Concept and clinical review. Cognitive
Screening Instruments. Chapter 6. P.111-151. Edited by A.J. Larner. Springer
2013.
Bibliography
76
95. Gill DJ, Freshman A, Blender JA, Ravina B. The Montreal cognitive assessment
as a screening tool for cognitive impairment in Parkinson’s disease. Mov Disord
2008;23:1043–1046.
96. Zadikoff C, Fox SH, Tang-Wai DF, et al. A comparison of the mini mental state
exam to the Montreal cognitive assessment in identifying cognitive deficits in
Parkinson’s disease. Mov Disord 2008;23:297–299.
97. Nazem S, Siderowf AD, Duda JE, et al. Montreal cognitive assessment
performance in patients with Parkinson’s disease with “normal” global cognition
according to minimental state examination score. J Am Geriatr Soc 2009;57:
304–308.
98. Mathuranath PS, Nestor PJ, Berrios GE, Rakowicz W, Hodges JR. A brief
cognitive test battery to differentiate Alzeimer’s disease and frontotemporal
dementia. Neurology 2000;55:1613–1620.
99. Reyes MA, Perez-Lloret S, Roldan Gerschcovich E, Martin ME, Leiguarda R,
Merello M. Addenbrooke’s Cognitive Examination validation in Parkinson’s
disease. Eur J Neurol. 2009;16(1):142-7.
100. Mathuranath PS, Hodges JR, Mathew R, Cherian PJ, George A, Bak TH.
Adaptation of the ACE for a Malayalam speaking population in southern India.
Int J Geriatr Psychiatry. 2004;19(12):1188-94.
101. Mathuranath PS, Cherian JP, Mathew R, Alexander A, Sarma S. Mini mental
state examination and the Addenbrooke’s cognitive examination: effect of
education and norms for a multicultural population. Neurol India 2007;55:106–
110.
Bibliography
77
102. Beck AT,Ward CH, Mendelson M, Mock J, Rraugh J. An inventory for
measuring depression. Arch Gen Psychiatry 1961;4:561–571.
103. Fahn S, Elton RL, and members of the UPDRS development committee. Unified
Parkinson’s rating scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M,
editors. Recent developments in Parkinson’s disease. Florham Park (NJ):
MacMillan; 1987. p153–164.
Annexure
Abbreviations
ACE- Addenbrooke’s Cognitive Examination AD-Alzheimers isease BDI- Beck’s Depression Inventory H&Y stage- Hoehn and Yahr stage LEDD- Levodopa equivalent dose MCI- Mild cognitive impairment MDRS-Mattis Dementia Rating Scale MDS- Movement Disorder Society MMSE- Mini-Mental Status Examination MoCA- Montreal Cognitive Assessment MoCA-M- Montreal Cognitive assessment-Malayalam NMS- Nonmotor symptoms PD-Parkinson’sdisease PD-CRS-Parkinson’s Disease-Cognitive Rating scale PDD- Parkinson’s disease dementia QOL- Quality of life SCOPA-COG-Scales for Outcomes of Parkinson’s disease–Cognition UKPDSBB- United Kingdom Parkinson’s Disease Society Brain Bank criteria UPDRS- Unified Parkinson’s Disease rating Scale
PROFORMA- FOR NORMAL CONTROLS Validation of the Malayalam Version of the Montreal Cognitive Assessment (MoCA) Scale and a Prospective Evaluation of Mild
Cognitive Impairment in Parkinson’s disease Using the Malayalam version (“MoCA-M”).
Date of Evaluation: 1. Subject details and history:
Name: Age:
Gender:
Level of Education: Total number of years of formal education:
Marital status:
Address:
Telephone No:
Details of any medical illnesses:
2. Details of any Medications which the subject is taking
Present Medications Total Daily Dose Duration of Exposure Dosing Schedule
3. Clinical Examination:
4. Neuropsychological evaluation:
MoCA score: Total
ACE- Total score:
MMSE:
BDI score:
PROFORMA- FOR PD PATIENTS Validation of the Malayalam Version of the Montreal Cognitive
Assessment (MoCA-M) Scale and a Prospective Evaluation of Mild Cognitive Impairment in Parkinson’s disease Using Malayalam
version (MoCA-M). Date of Evaluation:
1. Patient’s details and history:
Name: Hospital no:
Age: Gender: Level of Education: Total number of years of formal education: Marital status: Address: Telephone No: Duration of disease: Age at onset: Type of Parkinson’s disease: Tremor Dominant / Rigid Bradykinetic / mixed Side of onset : Right/ Left / Can’t say Motor fluctuations: Yes/ No Duration of MF: Dyskinesia: Duration: Type: Other medical illnesses: Family History of PD: No of family members affected: Non-motor Symptoms: Sleep dysfunction: Description: Hallucinations: Description: Other psychotic features: Impulse control disorders: Memory dysfunction: Other Cognitive symptoms: Description: Urinary disturbances: Other autonomic symptoms: Constipation: Other GI symptoms: Any other non-motor symptoms: Description:
2. Details of Medications Present Medications Total Daily Dose Duration of Exposure Dosing Schedule LEDD: Past Medications: Dose Duration of Exposure Anticholinergics (Specify) Amantadine:
3. Clinical Examination: “On” “Off” UPDRS I : UPDRS II: UPDRS III: UPDRS IV A: UPDRS IV B: Hoehn & Yahr stage:
4. Neuropsychological evaluation: MoCA score: Total ACE- Total score: MMSE: BDI score: