nondopaminergic and nonmotor symptoms of parkinson 's disease ( pd ) , which include psychiatric , autonomic , and gastrointestinal symptoms , are sometimes present before a diagnosis of pd and almost inevitably emerge with the disease progression .
in contrast to motor symptoms of pd , nonmotor symptoms have been poorly recognized and inadequately treated .
however , methods for recognizing and quantifying the nonmotor symptoms of pd have become a new focus of research that will form the basis for improved treatments . among the nonmotor symptoms ,
cognitive impairment adversely influences their activities of daily living and quality of life   and worsens caregiver burden .
a community - based study found that within a group of patients with a diagnosis of pd of at least 20 years , 83% had experienced dementia , and a similar number of patients had experienced frequent falls ( 87% ) , moderate dysarthria ( 81% ) , visual hallucinations ( 74% ) , or urinary incontinence ( 71% ) . in pd dementia
( pd - d ) patients , -synuclein pathology can be widespread in the cerebral cortex .
in addition , there is less acetylcholinesterase activity in the cerebral cortex of pd - d patients than of alzheimer 's disease patients .
moreover , clinical studies have reported on the effectiveness of cholinesterase inhibitors for treating cognitive impairment in pd - d patients .
the prevalence of cognitive dysfunction among pd patients has led to the recognition that a diagnostic criterion is needed for pd - d . as a result ,
the movement disorder society task force published diagnostic criteria for pd - d in 2007   and simultaneously proposed a practical diagnostic procedure for pd - d with the aim of its widespread international application .
level i testing includes a simple and short algorithm based on current cognitive tools that can be used in an office or at the bedside .
it is considered a screening tool for diagnosing pd - d , whereas level ii testing provides a more detailed assessment that characterizes the components of pd - d and monitors the elements that may be responsive to intervention .
level i testing was designed as a screening tool for use in the clinic and in clinical trials .
although it has been used in practice , no study has yet verified its validity or utility in a large sample of pd patients . in this study , we used level i testing on 304 pd patients with the objective of determining which patients would be diagnosed with pd - d and what impairments would be diagnosed among the 4 cognitive domains tested .
the subjects included in our study were japanese patients with idiopathic pd who were clinically diagnosed and treated by board - certified neurologists at 1 of the 13 participating institutions between july and september 2011 .
a diagnosis of pd was made according to the uk parkinson 's disease society brain bank criteria   as well as a differential diagnosis .
the study design and protocol were approved by the ethics committees for human research of the keio university school of medicine and all the participating institutions .
this was a cross - sectional study which examined the clinical and neurological features of these pd patients , including sex , age at the assessment , education , disease duration , and the hoehn and yahr ( h&y ) stage .
their cognitive function was evaluated with the japanese versions of the mini - mental state examination ( mmse )   and montreal cognitive assessment ( moca ) .
the mmse consists of 10 subtests scored to a total of 30 points : pentagon copying ( 1 point ) , serial 7 subtraction ( 5 points ) , immediate ( 3 points ) and delayed 3-word recall ( 3 points ) , naming ( 2 points ) , repeating a sentence ( 1 point ) , 3-stage commands ( 3 point ) , reading a sentence ( 1 point ) , writing a sentence ( 1 point ) , and orientation to time and place ( 10 points ) .
the moca consists of 12 subtests also scored to a total of 30 points : cube copying ( 1 point ) , clock drawing ( 3 points ) , trail making ( 1 point ) , phonemic fluency ( 1 point ) , verbal abstraction ( 2 points ) , digit span ( 2 points ) , serial 7 subtraction ( 3 points ) , target tapping ( 1 point ) , delayed 5-word recall ( 5 points ) , naming ( 3 points ) , repeating 2 sentences ( 2 points ) , and orientation to time and place ( 6 points ) .
we used the algorithm for level i testing to examine the present patient population ( table 1 ) . in this algorithm ,
the diagnosis of pd - d is based on the following 5 criteria : ( 1 ) diagnosis of pd , ( 2 ) pd developed prior to the onset of dementia , ( 3 ) a decreased global cognitive efficiency , ( 4 ) a cognitive deficiency that impairs daily life , and ( 5 ) impairment in > 1 cognitive domain . in this study , however , we did not investigate whether cognitive deficits were severe enough to affect daily living ( item 4 , typically assessed with a caregiver interview or the pill questionnaire ) .
for item 5 , the results of the following subtests of the moca and mmse were used : serial 7 subtraction (  seven backward in table 1 ) , phonemic fluency (  lexical fluency ) , and clock drawing from the moca , and pentagon copying (  mmse pentagons ) and delayed 3-word recall from the mmse .
memory for delayed 3-word recall ( table 1 ) . in the months reversed test , the patient must name the months in reverse order .
however , japanese months are named by number , which is different from their naming in english ; thus , the months reversed test was excluded from this study . according to the level
i testing procedures , test results that indicated impairment were : 2 incorrect responses on the seven backward test , a score of 9 words in the lexical fluency test , an inability to correctly draw the clock face or clock hands pointing to the correct time in the clock drawing test , an inability to correctly draw 2 pentagons that overlap in the pentagon copying test , and 1 word missing in the 3-word recall test .
the jmp software version 8.0 ( sas institute , tokyo , japan ) was used for all statistical analyses .
the level of statistical significance was defined as p < 0.05 . a one - way anova and the tukey - kramer hsd test
the subjects included in our study were japanese patients with idiopathic pd who were clinically diagnosed and treated by board - certified neurologists at 1 of the 13 participating institutions between july and september 2011 .
a diagnosis of pd was made according to the uk parkinson 's disease society brain bank criteria   as well as a differential diagnosis .
the study design and protocol were approved by the ethics committees for human research of the keio university school of medicine and all the participating institutions .
this was a cross - sectional study which examined the clinical and neurological features of these pd patients , including sex , age at the assessment , education , disease duration , and the hoehn and yahr ( h&y ) stage .
their cognitive function was evaluated with the japanese versions of the mini - mental state examination ( mmse )   and montreal cognitive assessment ( moca ) .
the mmse consists of 10 subtests scored to a total of 30 points : pentagon copying ( 1 point ) , serial 7 subtraction ( 5 points ) , immediate ( 3 points ) and delayed 3-word recall ( 3 points ) , naming ( 2 points ) , repeating a sentence ( 1 point ) , 3-stage commands ( 3 point ) , reading a sentence ( 1 point ) , writing a sentence ( 1 point ) , and orientation to time and place ( 10 points ) .
the moca consists of 12 subtests also scored to a total of 30 points : cube copying ( 1 point ) , clock drawing ( 3 points ) , trail making ( 1 point ) , phonemic fluency ( 1 point ) , verbal abstraction ( 2 points ) , digit span ( 2 points ) , serial 7 subtraction ( 3 points ) , target tapping ( 1 point ) , delayed 5-word recall ( 5 points ) , naming ( 3 points ) , repeating 2 sentences ( 2 points ) , and orientation to time and place ( 6 points ) .
we used the algorithm for level i testing to examine the present patient population ( table 1 ) . in this algorithm ,
the diagnosis of pd - d is based on the following 5 criteria : ( 1 ) diagnosis of pd , ( 2 ) pd developed prior to the onset of dementia , ( 3 ) a decreased global cognitive efficiency , ( 4 ) a cognitive deficiency that impairs daily life , and ( 5 ) impairment in > 1 cognitive domain . in this study , however , we did not investigate whether cognitive deficits were severe enough to affect daily living ( item 4 , typically assessed with a caregiver interview or the pill questionnaire ) .
for item 5 , the results of the following subtests of the moca and mmse were used : serial 7 subtraction (  seven backward in table 1 ) , phonemic fluency (  lexical fluency ) , and clock drawing from the moca , and pentagon copying (  mmse pentagons ) and delayed 3-word recall from the mmse .
however , japanese months are named by number , which is different from their naming in english ; thus , the months reversed test was excluded from this study . according to the level
i testing procedures , test results that indicated impairment were : 2 incorrect responses on the seven backward test , a score of 9 words in the lexical fluency test , an inability to correctly draw the clock face or clock hands pointing to the correct time in the clock drawing test , an inability to correctly draw 2 pentagons that overlap in the pentagon copying test , and 1 word missing in the 3-word recall test .
the jmp software version 8.0 ( sas institute , tokyo , japan ) was used for all statistical analyses .
the level of statistical significance was defined as p < 0.05 . a one - way anova and the tukey - kramer hsd test
a detailed description of the demographics of the 304 pd patients included in our study has been reported elsewhere . briefly , the subjects were 166 men and 138 women with a mean age  sd of 70.6  8.3 ( range : 42 - 90 ) years ; their education lasted 12.5  2.6 ( range : 1 - 20 ) years , the disease duration was 6.6  5.1 ( range : 0.2 - 30.1 ) years , and their h&y stage was 2.7  0.7 ( range : 1 - 5 ) . the subjects were grouped into tertiles according to their total moca score ( table 2 ) .
similarly , the subjects were grouped into tertiles according to their total mmse score ( table 3 ) .
the single subtest scores decreased significantly as the total moca scores decreased from the high - moca - score group to the middle- and low - moca - score groups ( p < 0.05 ) .
exceptionally , the decreases in scores for the naming , target tapping , and orientation tests from the high- to the middle - moca - score group were not significantly different .
therefore , the decline in the total moca score mirrors a decline in the scores for almost all the subtests .
naming and orientation were preserved ( > 80% ) even in the low - moca - score group .
in contrast , sentence repeating , phonemic fluency , and delayed recall scores decreased remarkably ( < 70% ) even in the high - moca - score group .
trail making was preserved in the high - moca - score group but decreased steeply in the middle- and low - moca - score groups .
the scores for the 10 mmse subtests are presented by group in figure 1b . for most of the subtests ( 7 of 10 ) , the scores failed to show a significant decrease from the high- to the middle - mmse - score group , and the scores for the naming subtest failed to decrease even in the low - mmse - score group .
all domains were preserved ( > 90% ) in the high - mmse - score group , indicating that no mmse subtest was significative for these pd patients ( fig .
a significant decrease was observed only for the serial 7 subtraction and delayed recall subtests in the low - mmse - score group ( < 50% , p < 0.05 ) .
for example , the moca includes a 5-word delayed recall test , whereas the mmse provides a 3-word delayed recall test ; 5-word recall according to the moca was < 70% even in the high - moca - score group , whereas 3-word recall according to the mmse was relatively preserved ( fig . 1 , 2 ) .
in addition , the moca includes a subtest in which 2 sentences are repeated , whereas the mmse includes a subtest in which 1 sentence is repeated .
the repeating 2 sentences subtest of the moca showed a score < 70% in the high - moca - score group , but the score for the repeating a sentence subtest of the mmse was preserved even in the low - mmse - score group .
items 1 ( diagnosis of pd ) and 2 ( dementia preceding pd ) in level i testing ( table 1 ) were applicable to the subjects participating in this study . for item 3 ( decreased global cognitive efficiency ) , 105 subjects ( 34.5% ) showed an mmse score < 26 . with respect to item 5 ( dysfunction in > 1 cognitive domain ) , we observed that 53 subjects ( 17.4% ) showed no impairment in any cognitive domain , whereas the remaining subjects showed impairments in 1 ( n = 74 ; 24.3% ) , 2 ( n = 87 ; 28.6% ) , 3 ( n = 74 ; 24.3% ) , or 4 ( n = 16 ; 5.3% ) cognitive domains .
therefore , 177 subjects ( 58.2% ) showed impairments in 2 cognitive domains . among these 177 subjects ,
99 also had mmse scores < 26 ( 32.6% of all subjects ; 94.3% of the total group with mmse scores < 26 ) and therefore met the diagnostic criteria for pd - d . only 6 subjects ( 5.7% of 105 subjects ) with mmse scores < 26 did not meet the diagnostic criteria for pd - d , because they had only 1 impaired cognitive domain .
of the 105 subjects with mmse scores < 26 , most showed impairments in 3 cognitive domains ( n = 62 ; 59.0% ) .
figure 3 shows the number of subjects with mmse scores < 26 or 26 , along with the number of impaired domains .
no subject with an mmse score < 26 was without impairment in any domain . among the subjects with mmse scores 26 ( n = 199 )
, we observed 1 ( n = 68 ; 34.2% ) , 2 ( n = 65 ; 32.7% ) , 3 ( n = 12 ; 6.0% ) , and 4 ( n = 1 ; 0.5% ) impaired domains ; 53 ( 26.6% ) had no impairment in any cognitive domain .
figure 4 shows the proportions of subjects with mmse scores < 26 or 26 , along with the number of impaired domains .
subjects with mmse scores 26 accounted for the majority of subjects with 1 impaired domain , and they accounted for 74.7% of subjects with 2 impaired domains . in contrast , subjects with mmse scores < 26 accounted for the majority of subjects with 3 or 4 impaired domains .
this finding was as expected because patients with lower mmse scores should have an increased likelihood of being affected in more cognitive domains .
figure 5a shows the numbers of subjects with impairments for each of the 4 cognitive domains .
the most common impairment was executive dysfunction ( 224 subjects ; 73.7% ) , followed by memory ( n = 161 ; 53.0% ) and attention ( n = 119 ; 39.1% ) impairments .
visuospatial functional impairments were the least common and were apparent in only 30 subjects ( 9.9% ) .
of the 224 subjects who showed executive dysfunction , most exhibited impairment in lexical fluency ( 180 subjects ; 80.4% ) or clock drawing ( n = 133 ; 59.4% ) , whereas 89 subjects ( 39.7% ) displayed impairments in both ( fig .
the most common combinations in the group with mmse scores 26 were executive dysfunction alone ( 49 subjects ; 24.6% ) and executive dysfunction with memory impairment ( n = 47 ; 23.6% ) , followed by executive dysfunction with attention impairment ( n = 16 ; 9.5% ) and memory impairment alone ( n = 15 ; 7.5% ) .
the most common combination of impaired cognitive domains in the group with mmse scores < 26 was executive dysfunction with both memory and attention impairments ( n = 54 ; 51.4% ) , followed by impairments in all 4 domains ( n = 15 ; 14.3% ) .
interestingly , visuospatial impairment was always accompanied by executive dysfunction ; however , visuospatial impairment alone , or in combination with attention , memory , or both attention and memory impairments , did not occur in any of the subjects .
for the purpose of screening pd patients for dementia , it is necessary to use a test in which achievement does not decline in pd patients who have normal global cognitive efficiency ( as measured by the total mmse or moca score ) but declines in those patients with impaired global cognitive efficiency indicative of dementia . with regard to the hypothesis that an appropriate test is one in which the high- and middle - total - score groups by the mmse or the moca maintain a score 70% while the low - total - score group scores < 70% , the copy cube , draw clock , verbal abstraction , digit span , target tapping , and serial 7 subtraction tests of the moca ( marked # in fig .
2a ) and the serial 7 subtraction and 3-word delayed recall tests of the mmse ( marked # in fig .
2b ) are considered appropriate . in level i testing , this includes the clock drawing , serial 7 subtraction , and delayed 3-word recall subtests , but not the phonemic fluency or pentagon copying subtests . as regards evaluating executive function ,
scores for the phonemic fluency test declined markedly to approximately 50% in the high - moca - score group , whose scores ( 24 - 30 ) were consistent with pd without dementia .
the other subtest that evaluates executive function in level i testing is the clock drawing test .
scores for this test declined to < 70% only in the low - moca - score group .
this suggests the clock drawing test may be more appropriate than the phonemic fluency test for screening for a decline in executive function in pd - d . on the other hand , when evaluating visuospatial function , scores for the pentagon copying test stayed at 70% even in the low - mmse - score group , whose scores ( 12 - 25 ) were below the 26-point cutoff for pd - d .
the authors of the original moca test indicated that the cube copying and clock drawing tests are concerned with visuospatial function , but in level i testing , the clock drawing test is used for executive function . for the cube copying test , the authors stated that  if any of the following criteria are not met , the abnormal result was assigned : ( 1 ) drawing must be 3 dimensional , ( 2 ) all lines are drawn , ( 3 ) no line is added , ( 4 ) lines are relatively parallel and their length is similar . applied to the 304 subjects in the present study , 101 were classified as abnormal according to the cube copying test , including 43 subjects in the group with mmse scores 26 and 58 subjects in the group with mmse scores < 26 .
these are far more than the 30 subjects with abnormal results for the pentagon copying test , and almost as many as the 119 subjects who were categorized as abnormal in attention by the serial 7 subtraction test .
a detailed description of the demographics of the 304 pd patients included in our study has been reported elsewhere . briefly , the subjects were 166 men and 138 women with a mean age  sd of 70.6  8.3 ( range : 42 - 90 ) years ; their education lasted 12.5  2.6 ( range : 1 - 20 ) years , the disease duration was 6.6  5.1 ( range : 0.2 - 30.1 ) years , and their h&y stage was 2.7  0.7 ( range : 1 - 5 ) .
the subjects were grouped into tertiles according to their total moca score ( table 2 ) .
similarly , the subjects were grouped into tertiles according to their total mmse score ( table 3 ) .
the single subtest scores decreased significantly as the total moca scores decreased from the high - moca - score group to the middle- and low - moca - score groups ( p < 0.05 ) .
exceptionally , the decreases in scores for the naming , target tapping , and orientation tests from the high- to the middle - moca - score group were not significantly different .
therefore , the decline in the total moca score mirrors a decline in the scores for almost all the subtests . the differences between the 12 moca subtests are presented in figure 2a .
naming and orientation were preserved ( > 80% ) even in the low - moca - score group . in contrast ,
sentence repeating , phonemic fluency , and delayed recall scores decreased remarkably ( < 70% ) even in the high - moca - score group .
trail making was preserved in the high - moca - score group but decreased steeply in the middle- and low - moca - score groups .
the scores for the 10 mmse subtests are presented by group in figure 1b . for most of the subtests ( 7 of 10 ) , the scores failed to show a significant decrease from the high- to the middle - mmse - score group , and the scores for the naming subtest failed to decrease even in the low - mmse - score group .
all domains were preserved ( > 90% ) in the high - mmse - score group , indicating that no mmse subtest was significative for these pd patients ( fig .
a significant decrease was observed only for the serial 7 subtraction and delayed recall subtests in the low - mmse - score group ( < 50% , p < 0.05 ) .
for example , the moca includes a 5-word delayed recall test , whereas the mmse provides a 3-word delayed recall test ; 5-word recall according to the moca was < 70% even in the high - moca - score group , whereas 3-word recall according to the mmse was relatively preserved ( fig . 1 , 2 ) .
in addition , the moca includes a subtest in which 2 sentences are repeated , whereas the mmse includes a subtest in which 1 sentence is repeated .
the repeating 2 sentences subtest of the moca showed a score < 70% in the high - moca - score group , but the score for the repeating a sentence subtest of the mmse was preserved even in the low - mmse - score group .
items 1 ( diagnosis of pd ) and 2 ( dementia preceding pd ) in level i testing ( table 1 ) were applicable to the subjects participating in this study . for item 3 ( decreased global cognitive efficiency ) , 105 subjects ( 34.5% ) showed an mmse score < 26 . with respect to item 5 ( dysfunction in > 1 cognitive domain ) , we observed that 53 subjects ( 17.4% ) showed no impairment in any cognitive domain , whereas the remaining subjects showed impairments in 1 ( n = 74 ; 24.3% ) , 2 ( n = 87 ; 28.6% ) , 3 ( n = 74 ; 24.3% ) , or 4 ( n = 16 ; 5.3% ) cognitive domains .
therefore , 177 subjects ( 58.2% ) showed impairments in 2 cognitive domains . among these 177 subjects ,
99 also had mmse scores < 26 ( 32.6% of all subjects ; 94.3% of the total group with mmse scores < 26 ) and therefore met the diagnostic criteria for pd - d .
only 6 subjects ( 5.7% of 105 subjects ) with mmse scores < 26 did not meet the diagnostic criteria for pd - d , because they had only 1 impaired cognitive domain .
of the 105 subjects with mmse scores < 26 , most showed impairments in 3 cognitive domains ( n = 62 ; 59.0% ) .
figure 3 shows the number of subjects with mmse scores < 26 or 26 , along with the number of impaired domains .
no subject with an mmse score < 26 was without impairment in any domain . among the subjects with mmse scores 26 ( n = 199 )
, we observed 1 ( n = 68 ; 34.2% ) , 2 ( n = 65 ; 32.7% ) , 3 ( n = 12 ; 6.0% ) , and 4 ( n = 1 ; 0.5% ) impaired domains ; 53 ( 26.6% ) had no impairment in any cognitive domain .
figure 4 shows the proportions of subjects with mmse scores < 26 or 26 , along with the number of impaired domains .
subjects with mmse scores 26 accounted for the majority of subjects with 1 impaired domain , and they accounted for 74.7% of subjects with 2 impaired domains .
in contrast , subjects with mmse scores < 26 accounted for the majority of subjects with 3 or 4 impaired domains .
this finding was as expected because patients with lower mmse scores should have an increased likelihood of being affected in more cognitive domains .
figure 5a shows the numbers of subjects with impairments for each of the 4 cognitive domains .
the most common impairment was executive dysfunction ( 224 subjects ; 73.7% ) , followed by memory ( n = 161 ; 53.0% ) and attention ( n = 119 ; 39.1% ) impairments .
visuospatial functional impairments were the least common and were apparent in only 30 subjects ( 9.9% ) .
of the 224 subjects who showed executive dysfunction , most exhibited impairment in lexical fluency ( 180 subjects ; 80.4% ) or clock drawing ( n = 133 ; 59.4% ) , whereas 89 subjects ( 39.7% ) displayed impairments in both ( fig .
the most common combinations in the group with mmse scores 26 were executive dysfunction alone ( 49 subjects ; 24.6% ) and executive dysfunction with memory impairment ( n = 47 ; 23.6% ) , followed by executive dysfunction with attention impairment ( n = 16 ; 9.5% ) and memory impairment alone ( n = 15 ; 7.5% ) .
the most common combination of impaired cognitive domains in the group with mmse scores < 26 was executive dysfunction with both memory and attention impairments ( n = 54 ; 51.4% ) , followed by impairments in all 4 domains ( n = 15 ; 14.3% ) .
interestingly , visuospatial impairment was always accompanied by executive dysfunction ; however , visuospatial impairment alone , or in combination with attention , memory , or both attention and memory impairments , did not occur in any of the subjects .
for the purpose of screening pd patients for dementia , it is necessary to use a test in which achievement does not decline in pd patients who have normal global cognitive efficiency ( as measured by the total mmse or moca score ) but declines in those patients with impaired global cognitive efficiency indicative of dementia . with regard to the hypothesis that an appropriate test is one in which the high- and middle - total - score groups by the mmse or the moca maintain a score 70% while the low - total - score group scores < 70% , the copy cube , draw clock , verbal abstraction , digit span , target tapping , and serial 7 subtraction tests of the moca ( marked # in fig . 2a ) and the serial 7 subtraction and 3-word delayed recall tests of the mmse ( marked # in fig .
in level i testing , this includes the clock drawing , serial 7 subtraction , and delayed 3-word recall subtests , but not the phonemic fluency or pentagon copying subtests . as regards evaluating executive function ,
scores for the phonemic fluency test declined markedly to approximately 50% in the high - moca - score group , whose scores ( 24 - 30 ) were consistent with pd without dementia .
the other subtest that evaluates executive function in level i testing is the clock drawing test .
scores for this test declined to < 70% only in the low - moca - score group .
this suggests the clock drawing test may be more appropriate than the phonemic fluency test for screening for a decline in executive function in pd - d . on the other hand , when evaluating visuospatial function , scores for the pentagon copying test stayed at 70% even in the low - mmse - score group , whose scores ( 12 - 25 ) were below the 26-point cutoff for pd - d .
the authors of the original moca test indicated that the cube copying and clock drawing tests are concerned with visuospatial function , but in level i testing , the clock drawing test is used for executive function . for the cube copying test , the authors stated that  if any of the following criteria are not met , the abnormal result was assigned : ( 1 ) drawing must be 3 dimensional , ( 2 ) all lines are drawn , ( 3 ) no line is added , ( 4 ) lines are relatively parallel and their length is similar . applied to the 304 subjects in the present study , 101 were classified as abnormal according to the cube copying test , including 43 subjects in the group with mmse scores 26 and 58 subjects in the group with mmse scores < 26 .
these are far more than the 30 subjects with abnormal results for the pentagon copying test , and almost as many as the 119 subjects who were categorized as abnormal in attention by the serial 7 subtraction test .
some previous studies have examined the screening properties of level i testing for pd - d .
have demonstrated that level i testing is more sensitive for the detection of pd - d , detecting up to 22% more cases than the dsm - iv . di battista et al .  
validated level i testing in comparison with the dsm - iv criteria for pd - d and revealed its relatively lower sensitivity ( 78% ) but high specificity ( 95.5% ) with a 12% prevalence of pd - d in 76 pd patients .
the authors raised their doubts about the sensitivity of an mmse cutoff value of 26 , stating this to be the main cause of false negatives , and also pointed out that more sensitive cognitive domain - related psychometric tests would maximize the screening property of level i testing .
compared level i testing with full neuropsychological testing for detecting pd - d in 91 pd patients and found that 7.7% of the subjects met the level i testing criteria , while 16.5% of the subjects were classified as pd - d by full neuropsychological testing .
they revealed that level i testing showed 100% specificity but only 46.7% sensitivity for diagnosing pd - d compared with the full neuropsychological assessment .
they showed that the low sensitivity is largely due to the total mmse cutoff values for decreased global cognitive efficiency and the 15-item geriatric depression scale score for excluding depression .
we found that 34.5% of all pd patients examined in the present study had mmse scores < 26 .
most of these patients ( 94.3% ) were impaired in 2 cognitive domains and therefore were cases of probable pd - d .
many of these patients ( 59% ) showed impairment in 3 cognitive domains , and patients rarely showed impairment in a single cognitive domain .
at least 1 of these 4 cognitive domains was always impaired in pd patients with mmse scores < 26 . even among pd patients with mmse scores 26 , many had impairments in 1 or 2 cognitive domains , and the proportion of those with no impairment in any cognitive domain was 26.6% .
subjects with mmse scores 26 accounted for 75% of pd patients who had impairments in 2 cognitive domains , which was far more than in the group with mmse scores < 26 . among the cognitive domains , executive function , which was tested by the phonemic fluency and clock drawing subtests , was most frequently impaired ; visuospatial function , which was tested by the pentagon copying test , was least frequently impaired .
no patient showed visuospatial impairment alone , and an impaired visuospatial function was always accompanied by executive dysfunction . among the subjects in the group with mmse scores 26 , the most common combinations were executive dysfunction alone or executive dysfunction with memory impairment , each of which accounted for approximately 25% of these subjects . among the subjects in the group with mmse scores
< 26 , the combination of executive dysfunction with both attention and memory impairment was most frequent , accounting for approximately 50% of these subjects .
the inclusion of impairments in 2 cognitive domains as an item in level i testing stems from the conventional thinking behind the diagnostic criteria for dementia resulting from research on alzheimer 's disease .
level i testing includes 4 cognitive domains that may often be impaired in pd patients .
we showed that for the mmse and moca subtests , some test results were abnormal even among pd patients with mmse scores 26 .
this suggests that for dementia screening tools such as level i testing , it may be appropriate to use tests in which abnormalities are rare in patients with mmse scores 26 but tend to be common in those scoring < 26 .
thus , once tests that tend to yield abnormal scores even for pd patients with mmse scores 26 are included in a screening tool , its sensitivity for pd - d diagnosis will increase , even if its specificity will decrease . a total of 32.6% of the pd patients
had mmse scores < 26 and impairments in 2 cognitive domains , and may therefore have met the diagnostic criteria for probable pd - d by level i testing .
this point prevalence of pd - d in pd is similar to the mean value of 31.1% ( 95% ci : 20.1 - 42.1 ) reported in a systematic and critical review of previous studies , thus indicating the validity of level i testing .
the fact that 1 of the 5 tests concerning the 4 cognitive domains included in these diagnostic tests showed abnormal scores for the group of patients with mmse scores < 26 indicates the validity of these tests as a whole for pd - d screening .
however , the results of this study show that the moca clock drawing subtest might be more appropriate than the phonemic fluency test for revealing executive dysfunction when screening for pd - d .
the frequency of abnormal results for the mmse pentagon copying subtest was < 10% , and thus was markedly lower than for the other tests .
this is inconsistent with previous reports   which found that visuospatial function tends to be impaired in pd - d , and it may be necessary to replace this test with another that also examines visuospatial function .
item 4 ( activities of daily living ) in level i testing was not evaluated and no extensive neuropsychological assessment was done , because of which dementia was not accurately diagnosed for each subject .
therefore , this study could not address the validity , sensitivity , or specificity of level i testing regarding clinically diagnosed pd - d .
the months reversed test was not used as there was no japanese equivalent to this english subtest in level i testing ; therefore , we could not examine its validity .
by using the mmse and moca , level i testing for pd - d can evaluate both decreased global cognitive efficiency and impairments in cognitive domains that are vulnerable in pd - d .
level i testing is therefore regarded as a practical and useful tool for screening dementia in pd patients .
a total of 32.6% of the pd patients met the diagnostic criteria for probable pd - d . among the subjects with mmse scores
< 26 , the combination of impaired attention , executive dysfunction , and memory impairment was the most common ( 51.4% ) .
the months reversed test can not be used in japanese as a test for attention owing to linguistic nonequivalence .
the moca clock drawing test may be more appropriate than the phonemic fluency test as a measure of executive function .
perhaps consideration should be given to replacing the mmse pentagon copying test with a different test of visuospatial function , such as the moca cube copying test , to improve sensitivity when screening for pd - d .
 backgrounddementia is a new focus of research on improved treatment for parkinson 's disease ( pd ) . in 2007 , a screening tool for pd dementia ( pd - d ) was developed by the movement disorder society ( level i testing ) , which still requires verification by a large population study.methodswe conducted a cross - sectional and multicenter study including 13 institutions administering the mini - mental state examination ( mmse ) and montreal cognitive assessment ( moca ) to 304 pd patients ( mean age : 70.6  8.3 years ; mean hoehn and yahr stage : 2.7  0.7).resultsin all , 34.5% of the patients had mmse scores < 26 ; 94.3% of these patients had impairments in 2 cognitive domains and met the criteria for probable pd - d by level i testing . 
 executive dysfunction combined with attention and memory impairment was most common ( 51.4% ) . in the level 
 i subtests of executive function , the score for phonemic fluency declined by < 50% in patients with high moca scores ( 24 - 30 points ) and lacked specificity for pd - d . 
 no patient had visuospatial impairment ( measured by the pentagon copying subtest ) alone , and the score for pentagon copying stayed at 70% even in patients with low mmse scores ( 12 - 25 points ) , therefore lacking sensitivity for pd-d.conclusionslevel i testing with administration of the mmse and moca is a practical and efficient screening tool for pd - d . 
 however , the phonemic fluency and pentagon copying tests should be replaced by more specific / sensitive ones when screening for pd - d . 
Introduction
Subjects and Methods
Subjects
Assessments of Clinical and Neurological Features
Algorithm for Level I Testing
Statistical Analysis
Results
Subject Demographics
Differences among the MoCA and MMSE Tests
Application of Diagnostic Criteria for PD-D Screening (Level I Testing)
Possible Alternatives to Level I Testing
Discussion
Conclusions
Disclosure Statement