Abstract

We examined the utility of illusory contours (ICs) for the differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). Thirty-five probable DLB patients, 35 probable AD patients controlled by age, years of education, and Mini-Mental State Examination (MMSE) score, and 30 cognitively normal subjects controlled by age and years of education underwent visuoperceptual examinations including ICs, pentagon copying in MMSE, overlapping figures, clock drawing test, cube copying, and line orientation. Four items in ICs (ICs-4) were found to be significantly impaired in DLB compared with AD, and a sensitivity and a specificity of total score of ICs-4 were 88.6% and 37.1%, respectively. When a score of ICs-4 is combined with a 10-point scaled score of pentagon copying in MMSE, a sensitivity and a specificity were 77.1% and 82.9%, respectively. The present study suggests that ICs-4 can be included in neuropsychological examinations to assess visuoperceptual impairment in DLB.

Introduction

Dementia with Lewy bodies (DLB) is the second most common type of neurodegenerative dementia disease after Alzheimer's disease (AD) (Donaghy & McKeith, 2014). The core clinical features of DLB are cognitive fluctuation, recurrent visual hallucinations (VH), and parkinsonism (McKeith et al., 2005). Compared with AD, DLB typically presents significantly more severe and various psychotic symptoms, such as VH, auditory hallucinations, delusions, and depression from the early stage of disease progression (Simard, van Reekum, & Chohen, 2000). Among them, VH, one of the core features of DLB, can be observed in 55–70% of DLB patients (Farina et al., 2009; McKeith et al., 2005), and may be related to visuoperceptual impairment characteristic of DLB (Mori et al., 2000; Simard et al., 2000). These psychotic symptoms can be a psychological and physical burden for both patients and their family caregivers, and are often a risk factor for a decreased quality of life (Hurt et al., 2008).

Differentiation of DLB from AD can be challenging, but neuroimaging examinations such as dopamine transporter imaging (DaTscan) and fluorodeoxyglucose positron emission tomography (FDG-PET) are helpful. DaTscan using PET and single-photon emission computed tomography (SPECT) can be useful to detect Lewy body disease such as DLB and Parkinson's disease by examining low dopamine transporter uptake in the basal ganglia (Walker et al., 2007). When 18F-FDG-PET is used to assess regional cerebral hypometabolism, DLB patients tend to exhibit significantly more severe hypometabolism in the occipital lobe, particularly in the primary visual cortex, than AD patients, while there are no significant differences in other regions that are commonly affected in AD patients, including the posterior cingulate cortex and the parietotemporal association cortex (Minoshima et al., 2001; Shimomura et al., 1998).

In addition, neuropsychological examinations are helpful to differentiate DLB from AD. In the early stage, DLB patients tend to perform worse than AD patients in tasks on visuoperception, visuoconstruction, and spatial working memory, while AD patients usually achieve lower scores on memory and orientation tasks than DLB patients (Simard et al., 2000). Several studies reported impairment in copying tasks such as pentagon copying in the Mini-Mental State Examination (MMSE) and the Bender Gestalt Test in DLB patients (Ala, Hughes, Kyrouac, Ghobrial, & Elble, 2001; Mori et al., 2000; Murayama et al., 2007). In the clock drawing test (CDT), both DLB and AD patients may show disturbances in drawing a clock face; however, AD patients demonstrate greater improvement in copying a clock face, while DLB patients tend to show impairment in copying as well as drawing (Gnanalingham, Byrne, & Thornton, 1996; Nagahama, Okina, Suzuki, & Matsuda, 2008). Cube copying is reported to be useful in discriminating DLB from AD, when administered with MMSE and CDT (Palmqvist, Hansson, Minthon, & Londos, 2009), although both AD and DLB patients show impairment when cube copying alone is administered (Maeshima et al., 2004). Although the mechanism of such copying deficits has not yet been clarified, a deficit of the occipito-temporal areas may underlie drawing impairment in DLB patients (Cormack, Aarsland, Ballard, & Tovée, 2004). Other studies found impairment in visual discrimination based on length, size, and angle using neuropsychological examinations such as Benton's line orientation in DLB patients (Mosimann et al., 2004; Simard, van Reekum, & Myran, 2003). Impairment in line orientation can be associated with lesions in the right posterior parietal and occipito-parietal areas, within the dorsal visual stream (Tranel, Vianna, Manzel, Damasio, & Grabowski, 2009). Moreover, object perception tasks including overlapping figures are also helpful in detecting DLB (Mori et al., 2000). Deficits in overlapping figures are mainly associated with the inability to perceive more than two objects simultaneously and alternating visual attention, and these deficits commonly reflect impairment in the occipital and frontal lobes, respectively (Lezak, 1995).

In the present study, we investigated the utility of illusory contours (ICs) for detecting visuoperceptual impairment in DLB patients. ICs or subjective contours involve perception of lines, forms, and volumes in the absence of physical support (Murray & Herrmann, 2013). Illusory figures induced by ICs are usually perceived more brightly than the background and positioned in the foreground in front of other figures in the background (Goto & Tanaka, 2005). Recently, we reported the possibility of early detection of DLB by using ICs (Ota et al., 2014). We hypothesize that ICs can detect visuoperceptual impairment in DLB patients, and can be included in neuropsychological examinations to discriminate DLB from AD.

Methods

Subjects

For the present study, the subjects were recruited from the Memory Clinic in Juntendo Tokyo Koto Geriatric Medical Center from January 2013 to March 2014. In the Memory Clinic, all patients undergo MMSE (Folstein, Folstein, & McHugh, 1975) for assessing global cognitive function as a part of routine examinations. Out of dementia patients whom a psychiatrist, one of us, initially examined during the above period, we first selected 44 patients who were diagnosed with probable DLB according to the international clinical diagnostic criteria (McKeith et al., 2005). Secondly, out of patients who were diagnosed with probable AD based on the diagnostic criteria of AD (McKhann et al., 2011), 44 patients matched by age, years of education, and MMSE score with DLB patients were selected. Of these 88 patients, 18 patients who scored <10 on MMSE were excluded, because overall cognitive dysfunction can affect the results of visuoperceptual functions especially for AD patients (Cormack et al., 2004). Finally, 35 patients with probable DLB (DLB group) and 35 patients with probable AD (AD group) were chosen for the present study. All DLB patients except for one presented with recurrent VH at some stage of disease progression. At the time of visuoperceptual examinations, only 11 DLB patients complained of VH; the other 23 did not. All DLB and AD patients had received medications for dementia including donepezil and rivastigmine and/or medications for psychotic symptoms including quetiapine, risperidone, and Yokukansan. No notable immediate changes in cognitive functions and psychotic symptoms were observed after initiation of the antipsychotic treatments. None of the patients presented any physical symptoms as secondary effects of the antipsychotic treatments. In addition, 30 cognitively normal volunteers without any psychological or neurological diseases were recruited as controls (Normal group). Inclusion criteria for Normal group were MMSE score of 28 and higher, no complaint of memory decline, and no deficits observed in neuroimaging examinations. Normal group was matched by age and years of education with the DLB and AD groups. None of these patients and controls presented any ophthalmological abnormalities disturbing their daily life, and their visual acuity levels were sufficient to perform neuropsychological examinations. Demographics of the three groups are shown in Table 1. This study was approved by the Ethics Committee of Juntendo Tokyo Koto Geriatric Medical Center. Written informed consent was obtained from all patients or their caregivers.

Table 1.

Demographics, results of MMSE, and visuoperceptual examinations of three groups

Group DLB AD Normal Significant difference 
Age 79.1 (6.2) 78.3 (5.9) 75.7 (4.8) DLB = AD = Normal 
Years of education 12.0 (2.8) 10.9 (2.5) 13.5 DLB = AD = Normal 
Male : female 16 : 19 11 : 24 17 : 13 DLB = AD = Normal 
MMSE (10) 18.1 (3.9) 18.9 (3.0) 28.6 (1.3) DLB = AD < Normal 
Pentagon copying in MMSE (10) 6.4 (3.3) 9.5 (0.9) 9.9 (0.3) DLB < AD = Normal 
Overlapping figures (6) 3.8 (1.6) 5.1 (0.9) 5.7 (0.5) DLB < AD < Normal 
CDT (10) 6.5 (2.6) 7.7 (2.5) 9.5 (1.0) DLB = AD < Normal 
Cube copying (1) 0.3 (0.4) 0.5 (0.5) 0.8 (0.4) DLB = AD < Normal 
Line orientation (4) 2.3 (1.5) 3.1 (1.0) 3.9 (0.3) DLB < AD < Normal 
Group DLB AD Normal Significant difference 
Age 79.1 (6.2) 78.3 (5.9) 75.7 (4.8) DLB = AD = Normal 
Years of education 12.0 (2.8) 10.9 (2.5) 13.5 DLB = AD = Normal 
Male : female 16 : 19 11 : 24 17 : 13 DLB = AD = Normal 
MMSE (10) 18.1 (3.9) 18.9 (3.0) 28.6 (1.3) DLB = AD < Normal 
Pentagon copying in MMSE (10) 6.4 (3.3) 9.5 (0.9) 9.9 (0.3) DLB < AD = Normal 
Overlapping figures (6) 3.8 (1.6) 5.1 (0.9) 5.7 (0.5) DLB < AD < Normal 
CDT (10) 6.5 (2.6) 7.7 (2.5) 9.5 (1.0) DLB = AD < Normal 
Cube copying (1) 0.3 (0.4) 0.5 (0.5) 0.8 (0.4) DLB = AD < Normal 
Line orientation (4) 2.3 (1.5) 3.1 (1.0) 3.9 (0.3) DLB < AD < Normal 

Notes: Total score of each visuoperceptual examination is in parentheses; MMSE = Mini-Mental State Examination; CDT = clock drawing test; data for age, years of education, MMSE, and visuoperceptual examinations are presented as mean (SD).

Neuroimaging Examinations

For the accurate diagnosis of dementia diseases, all patients underwent brain magnetic resonance imaging (MRI) (1.5T scanner, MAGNETOM Symphony; Siemens, Munich, Germany) and 18F-FDG-PET (GE Healthcare, Chalfont St. Giles, UK) or N-isopropyl-[123I] p-iodoamphetamine (IMP) SPECT (Toshiba Medical Systems Corp., Tochigi, Japan). In both DLB and AD groups, brain MRI indicated normal to mild atrophy, including in the medial temporal lobe, and vascular change typical for their ages. 18F-FDG-PET or 123I-IMP SPECT showed hypometabolism or hypoperfusion in the occipital lobe and/or the posterior cingulate cortex and parietotemporal association cortex for almost all patients in the DLB group and in the posterior cingulate cortex and parietotemporal association cortex for almost all patients in the AD group, which were consistent with the characteristics of probable DLB and probable AD, respectively.

Neuropsychological Examinations

In addition to MMSE, all patients and controls underwent visuoperceptual examinations including pentagon copying in MMSE, overlapping figures, CDT, cube copying, line orientation, and ICs. For the total score of MMSE, pentagon copying was scored 0 for incorrect and 1 for correct, however, for the scoring of pentagon copying alone, we used 10-point scoring method described by Teng and Chui (1987) with a maximum point of 10 and a minimum point of 0 for more detailed evaluation. We administered overlapping figures in Visual Perception Tests for Agnosia (VPTA), which is a Japanese standardized assessment tool for agnosia (The Committee for the Visual Perception Test, 1997). The maximum score for overlapping figures in VPTA was six. For CDT, we followed the administration procedure described previously (Rouleau, Kennedy, & McGuire, 1992) with a maximum score of 10. A total score of 7 points or lower is considered to indicate impairment (Rouleau et al., 1992). Cube copying was scored as 0 for incorrect or 1 for correct following the scoring method described in the Administration and Scoring Manual for the Alzheimer's Disease Assessment Scale (Mohs, 1994). For line orientation, we adopted line orientation tasks used in previous studies, in which a subject is asked to match a single line with an angle to one of 11 lines presented at 18° in a semicircle (Mosimann et al., 2004; Simard et al., 2003). Line orientation included four items with a maximum score of four. The cut-off point of each visuoperceptual examination administered in the present study was not determined in the original or previous studies, except for CDT.

Illusory Contours

In the ICs, a total of 7 items (ICs-7) were used, three of which were figures and four of which were Japanese letters. For the figures, we used a solid white square with black discs (Fig. 1a), which is known as the Kanizsa figure, a Necker cube with black discs (Fig. 1b), and two overlapping triangles with black discs (Fig. 1c). For the Japanese letters, we created four items with a white letter with black shadow (Fig. 2a–d). Two of them have meanings (Fig. 2a means “ecology” and Fig. 2b means “smile” in Japanese), and other two (Fig. 2c and d) do not. Each figure and letter was printed in black on a white sheet of paper (21 × 29.7 cm). The subjects were presented with each sheet of paper with a figure or letters and asked “What figure/letters can you see?” The correct answer for Fig. 1a would be “a (white) square,” for Fig. 1b would be “a cube/dice/box” (or any descriptions that mean 3D square object), and for Fig. 1c would be “two (overlapping) triangles.” One point was given when the subjects answered the correct figure, and no point was given when the subjects answered incorrect figure, or answered “I don't know.” After the subjects answered orally, we asked them to trace with their fingers the shape of the object(s) they perceived. For the letters, one point was given when the subjects answered all the letters in an item correctly, and no point was given when the subjects answered even one letter incorrectly, or answered “I don’ know.” We wrote down the subjects' answers.

Fig. 1.

Illusory contour figures (a, b, c).

Fig. 1.

Illusory contour figures (a, b, c).

Fig. 2.

Illusory contour letters (a, b, c, d).

Fig. 2.

Illusory contour letters (a, b, c, d).

Statistics

One-way ANOVA and Tukey's post hoc test were used for age, years of education, total score of MMSE, pentagon copying in MMSE, overlapping figures, CDT, line orientation, and ICs. Chi square test was used for sex ratio and cube copying. Sub-analysis of DLB patients who presented or did not present VH at the time of visuoperceptual examinations was conducted using t-test. In all tests, the null hypothesis was rejected at a significance level of p < 0.05.

The sensitivities, specificities, and cut-off points of visuoperceptual examinations were calculated using a receiver operating characteristic (ROC) curve. Cut-off points were selected based on the highest Youden's index.

For ICs, in order to investigate which item can adequately discriminate DLB from AD, we first compared each item among the three groups using one-way ANOVA and Tukey's post hoc test. Then we selected items that demonstrated significant difference between DLB and AD. Finally, we combined ICs and each of other visuoperceptual examinations (ICs + pentagon copying, ICs + overlapping figures, ICs + CDT, ICs + cube copying, ICs + line orientation) and examined sensitivity and specificity of each combination to find which combination is the most sensitive for differentiation of DLB and AD.

Results

The demographics and results of MMSE and visuoperceptual examinations of the three groups (DLB, AD, and Normal groups) are presented in Table 1. There was no significant difference in age, years of education, and sex ratio among the three groups. Generally, male tends to have a higher risk for DLB than female (Nelson et al., 2010); however, in Japan, population of male in DLB is not as high as reported in Western counties (Iseki, 2010). Moreover, in our memory clinic, the sex ratio of male to female is 3 : 4. Therefore, more female patients were included in the present study than male patients. There was no significant difference in MMSE total score between the DLB and AD groups, although the Normal group scored significantly higher than the other two groups. Pentagon copying in MMSE and overlapping figures were significantly impaired in the DLB group compared with those in the AD and Normal groups, although there was no significant difference between the AD and Normal groups in pentagon copying, while the AD group showed significantly lower scores than the Normal group in overlapping figures. In CDT and cube copying, both DLB and AD groups scored significantly lower than the Normal group, although there was no significant difference between the DLB and AD groups. In line orientation, the DLB group scored significantly lower than the AD and Normal groups, and the AD group showed significantly lower scores than the Normal group.

Table 2 shows the percentages of correct answers for each item in ICs-7. When the rates of correct answers for each item in ICs-7 were compared among the three groups using one-way ANOVA and Tukey's post hoc test, four items (ICs-4) consisting of two figures (Fig. 1a and c) and two letters (Fig. 2a and b) showed significantly lower scores in DLB compared with AD group. When the total scores of ICs-7 and ICs-4 were compared, respectively, among the three groups using one-way ANOVA and Tukey's post hoc test, both ICs-7 and ICs-4 demonstrated significantly lower scores in DLB group than in AD and Normal groups, and in the AD group than in the Normal group.

Table 2.

Percentages of correct answers and total scores of illusory contours in three groups

Group  DLB AD Normal Significant difference 
Subtests 
Figures 48.6 74.3 93.3 DLB < AD = Normal 
34.3 57.1 86.7 DLB = AD < Normal 
60.0 82.9 100.0 DLB < AD = Normal 
Letters 14.3 40.0 70.0 DLB < AD < Normal 
8.6 37.1 66.7 DLB < AD < Normal 
8.6 20.0 70.0 DLB = AD < Normal 
8.6 22.9 73.3 DLB = AD < Normal 
Total score of IC-7 mean (SD1.9 (1.8) 3.3 (2.2) 5.6 (1.8) DLB < AD < Normal 
Total score of IC-4 mean (SD1.3 (1.2) 2.3 (1.3) 3.3 (1.0) DLB < AD < Normal 
Group  DLB AD Normal Significant difference 
Subtests 
Figures 48.6 74.3 93.3 DLB < AD = Normal 
34.3 57.1 86.7 DLB = AD < Normal 
60.0 82.9 100.0 DLB < AD = Normal 
Letters 14.3 40.0 70.0 DLB < AD < Normal 
8.6 37.1 66.7 DLB < AD < Normal 
8.6 20.0 70.0 DLB = AD < Normal 
8.6 22.9 73.3 DLB = AD < Normal 
Total score of IC-7 mean (SD1.9 (1.8) 3.3 (2.2) 5.6 (1.8) DLB < AD < Normal 
Total score of IC-4 mean (SD1.3 (1.2) 2.3 (1.3) 3.3 (1.0) DLB < AD < Normal 

Table 3 lists sensitivities, specificities, and cut-off points of each visuoperceptual examinations and the combinations of ICs-4 and other visuoperceptual examinations. The ROC curve indicated that ICs-7 showed sensitivity of 65.7% and specificity of 68.6% with a cut-off point of 2/3, while ICs-4 exhibited sensitivity of 88.6% and specificity of 37.1% with a cut-off point of 2/3. For the combination of ICs-4 and other visuoperceptual examinations, ICs-4 and pentagon copying was found to best differentiate DLB and AD in the present study, with a sensitivity of 77.1% and specificity of 82.9% with a cut-off point of 10/11.

Table 3.

Sensitivities, specificities, and cut-off points of visuoperceptual examinations

Visuoperceptual examinations (total scores) Sensitivity (%) Specificity (%) Cut-off point 
ICs-7 (7) 65.7 68.6 2/3 
ICs-4 (4) 88.6 37.1 2/3 
Pentagon copying (10) 68.6 88.6 8/9 
Overlapping figures (6) 62.9 82.9 4/5 
CDT (10) 76.7 46.4 8/9 
Cube copying (1) 74.3 48.6 0/1 
Line orientation (4) 54.3 77.1 2/3 
ICs-4 + pentagon copying (14) 77.1 82.9 10/11 
ICs-4 + overlapping figures (10) 68.6 74.3 6/7 
ICs-4 + CDT (14) 66.7 75.0 9/10 
ICs-4 + cube copying (5) 80.0 60.0 2/3 
ICs-4 + line orientation (8) 65.7 68.6 4/5 
Visuoperceptual examinations (total scores) Sensitivity (%) Specificity (%) Cut-off point 
ICs-7 (7) 65.7 68.6 2/3 
ICs-4 (4) 88.6 37.1 2/3 
Pentagon copying (10) 68.6 88.6 8/9 
Overlapping figures (6) 62.9 82.9 4/5 
CDT (10) 76.7 46.4 8/9 
Cube copying (1) 74.3 48.6 0/1 
Line orientation (4) 54.3 77.1 2/3 
ICs-4 + pentagon copying (14) 77.1 82.9 10/11 
ICs-4 + overlapping figures (10) 68.6 74.3 6/7 
ICs-4 + CDT (14) 66.7 75.0 9/10 
ICs-4 + cube copying (5) 80.0 60.0 2/3 
ICs-4 + line orientation (8) 65.7 68.6 4/5 

Sub-analysis of DLB patients with or without VH at the time of visuoperceptual examinations using t-test indicated no significant difference between the two DLB groups in any of the visuoperceptual examinations including ICs-4 (not shown in a table).

We also qualitatively examined the characteristics of the subjects' answers in ICs-4. For the figures, the answers of 10 of 35 patients in the DLB group referred to meaningful objects instead of geometric figures, such as “bird's head/beak,” “a flock of birds flying,” “a human head with a bob hairstyle,” “an apple and an orange,” and “cherry blossoms.” These kinds of answer were observed in two of 35 patients in the AD group and none of 30 controls in the Normal group. Of 10 DLB patients who perceived meaningful objects, eight patients complained of VH at the time of visuoperceptual examinations.

Discussion

In the present study, we investigated the utility of ICs for detecting visuoperceptual impairment in DLB. There is a previous study using ICs for differentiating DLB and posterior cortical atrophy, in which there were no significant differences in the ability of perceiving ICs between DLB and posterior cortical atrophy (Metzler-Baddeley, Baddeley, Lovell, Laffan & Jones, 2010). In our knowledge, however, this is the first study to use ICs in differentiating DLB from common type of AD with statistically valuable numbers of subjects. We found that DLB patients tend to exhibit impairment in perceiving ICs compared with AD patients or normal controls, and ICs-4 in particular demonstrated high sensitivity. Clinical diagnostic criteria for DLB (McKeith et al., 2005) present low clinical sensitivity and high clinical specificity (Huang & Halliday, 2013); therefore, neuropsychological examinations with high sensitivity should be useful for detecting DLB. We partly confirmed our hypothesis that ICs can be included in neuropsychological examinations to differentiate DLB from AD because of its high sensitivity, although ICs alone may not be efficient to detect DLB.

Pentagon copying in MMSE, overlapping figures, and line orientation were also significantly more impaired in DLB patients than in AD patients or normal controls, confirming the findings of previous studies (Ala et al., 2001; Mori et al., 2000; Mosimann et al., 2004). In CDT and cube copying, there was no significant difference between DLB and AD patients, supporting previous studies that showed that CDT and cube copying can be impaired in both DLB and AD, although the patterns of impairment may differ between these two diseases (Gnanalingham et al., 1996; Nagahama et al., 2008).

Perceiving ICs comprises at least three aspects: first, perception of borders; second, enhanced brightness of the illusory figure versus the background; and third, depth perception in which an illusory figure is positioned in the foreground in front of inducers (Goto & Tanaka, 2005). In the present study, figure b (Fig. 1b), letters c and d (Fig. 2c and d) did not differ significantly between DLB and AD. Figure b may seem more complex than other stimuli, and it may seem to present weaker brightness enhancement and depth perception than other figures. Letter c and d may also look more complex than letters a and b. In addition, since letters c and d do not have meanings, they might have been more challenging to be read. Therefore, figure b, letters c and d may require more complex cognitive processing than other stimuli, and are more likely to be influenced by overall cognitive functions. The mechanism of perceiving ICs is still unclear; however, the involvement of the early stage of visual processing (V1 and V2), which is related to pre-attentive visual processes, to the later stage of visual processing (the lateral occipital cortex; LOC), which involves visuospatial attention, is suggested (Murray & Herrmann, 2013). DLB is known to present deficits in the visual cortices including V1 and V2 (Minoshima et al. 2001), which are related to visuoperceptual impairment in DLB, although deficits in the visual cortices are not typically found in AD. Therefore, impairment in ICs may be related to dysfunction in the occipital lobe including the visual cortices in DLB patients, as shown by 18F-FDG-PET findings (Minoshima et al. 2001; Shimomura et al., 1998).

Among various types of visuoperceptual examinations for DLB and other dementia diseases, drawing or copying tasks such as CDT, cube copying, and pentagon copying in MMSE have been used prevalently (Ala et al., 2001; Palmqvist et al., 2009). Drawing or copying tasks have an advantage that they can assess visuoperceptual function as well as motor functions and certain domains of cognitive functions at the same time (Lezak, 1995). However, the results of drawing or copying task can be influenced by tremors in parkinsonism, which is one of the core clinical features of DLB (McKeith et al., 2005). Moreover, construction abilities are associated with global cognitive function in AD (Cormack et al., 2004). Therefore, drawing or copying task alone may be difficult to differentiate DLB and AD for the patients with moderate cognitive impairment, although it can be useful for the patients with mild cognitive impairment. For example, one study (Palmqvist et al., 2009) suggested the use of a combination of orientation scores in MMSE, cube copying and CDT, in which the mean MMSE scores was 24 for DLB and 24.5 for AD. However, for the patients with more severe cognitive impairment, visuoperceptual examinations with minimum impact from parkinsonism and construction abilities, such as ICs, overlapping figures and line orientation, need to be added to drawing or copying tasks for detecting visuoperceptual impairment in DLB. In the present study, among drawing or copying tasks, only pentagon copying in MMSE showed a significant difference between DLB and AD. MMSE is one of the most common cognitive assessment tools in geriatric clinical settings, and can be administered in everyday clinical practice. Therefore, adding MMSE to ICs-4 would be unlikely to stress the subjects.

In the present study, DLB patients tended to give meanings to perceived objects in ICs-4 such as “bird's head/beak” and “a human head with a bob hairstyle,” compared with AD patients. Yokoi et al. (2014) recently reported that, in a study using the Pareidolia test, DLB patients tended to perceive meaningful illusory objects in colored scenery pictures far more frequently than AD patients and normal controls. In addition, they indicated that the number of illusory responses in DLB patients was significantly correlated with both hallucination and delusional misidentification scores on the neuropsychiatric inventory (Yokoi et al., 2014). In the present study, 8 of 10 DLB patients who gave meanings to perceived objects in ICs-4 presented VH at the time of visuoperceptual examinations. These findings suggest that DLB patients are likely to give meanings to perceived objects in visual scenes and figures, and that there may be a relationship between the presence of VH and the tendency to perceive illusory objects in DLB patients. The present study, however, did not indicate significant differences in scores of ICs-4 and other visuoperceptual examinations between DLB patients with and without VH. This may be due to the fact that, although 11 DLB patients presented VH at the time of visuoperceptual examinations, 23 other DLB patients also had a history of VH at some stage of disease progression, with just one DLB patient having no history of VH. Further research on DLB patients with and without a history of VH may clarify the relationship between the presence of VH and ICs-4.

Some AD patients can present prominent visuoperceptual impairment, which is called visual variant AD. DLB and visual variant AD share common clinical features; for instance, both can exhibit visuoperceptual impairment in neuropsychological examinations and may present behavioral disturbances in daily life, such as difficulties in writing (Tang-Wai et al., 2004). There is a report of a case in which AD patients exhibited impairment in perceiving Arabic numbers of ICs (Hirayama, 2013). Careful observation of clinical features and radiological examinations including brain MRI, 18F-FDG-PET, and cardiac iodine-123-metaiodobenzylguanidine ([123I]-MIBG) scintigraphy as well as visuoperceptual examinations can increase the accuracy of detecting DLB (Gilman et al., 2005; Minoshima et al., 2001; Tang-Wai et al., 2004).

There are limitations to the present study. Firstly, this study had a small sample size. Secondly, although we used Kaniza figures, there are other types of IC figure that could be used, such as figures with lines (Murray & Herrmann, 2013). Further research with various types of IC figure may clarify the mechanisms of visuoperceptual impairment in DLB. Thirdly, although we suggested the utility of ICs-4 for detecting DLB in a Japanese population in the present study, ICs-4 with Japanese letters would not be suitable for people who are unfamiliar with the Japanese language. Modifications, such as using IC figures only or using letters that are familiar to the patients, may be needed when ICs-4 are used for people who are not familiar with the Japanese language.

In conclusion, the present study suggests that ICs-4 can be included in neuropsychological examinations to assess visuoperceptual impairment in DLB patients. ICs-4 alone can discriminate DLB from AD with sensitivity of 88.6% and specificity of 37.1% with a cut-off point of 2/3. When ICs-4 is administered with pentagon copying in MMSE with 10-point scale, sensitivity is 80.0% and specificity is 76.9% with a cut-off point of 11/12.

Acknowledgements

This study was supported by project research funding from Juntendo University for research on the early detection of neurodegenerative dementias using brain functional imaging examinations and neuropsychological examinations.

References

Ala
T. A.
Hughes
L. F.
Kyrouac
G. A.
Ghobrial
M. W.
Elble
R. J.
(
2001
).
Pentagon copying is more impaired in dementia with Lewy bodies than in Alzheimer's disease
.
Journal of Neurology, Neurosurgery & Psychiatry
 ,
70
,
483
488
.
Cormack
F.
Aarsland
D.
Ballard
C.
Tovée
M. J.
(
2004
).
Pentagon drawing and neuropsychological performance in Dementia with Lewy Bodies, Alzheimer's disease, Parkinson's disease and Parkinson's disease with dementia
.
International Journal of Geriatric Psychiatry
 ,
19
,
371
377
.
Donaghy
P. C.
McKeith
I. G.
(
2014
).
The clinical characteristics of dementia with Lewy bodies and a consideration of prodromal diagnosis
.
Alzheimer‘s
 
Research & Therapy
 ,
6
,
46
.
Farina
E.
Baglio
F.
Caffarra
P.
Magnani
G.
Scarpini
E.
Appollonio
I.
et al
(
2009
).
Frequency and clinical features of Lewy body dementia in Italian memory clinics
.
Actabiomedica
 ,
80
,
57
64
.
Folstein
M. F.
Folstein
S. E.
McHugh
P. R.
(
1975
).
“Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician
.
Journal of Psychiatric Research
 ,
12
,
189
198
.
Gilman
S.
Koeppe
R. A.
Little
R.
An
H.
Junck
L.
Giordani
B.
et al
(
2005
).
Differentiation of Alzheimer's disease from dementia with Lewy bodies utilizing positron emission tomography with [18F] fluorodeoxyglucose and neuropsychological testing
.
Experimental Neurology
 ,
191
,
S95
S103
.
Gnanalingham
K. K.
Byrne
E. F.
Thornton
A.
(
1996
).
Clock-face drawing to differentiate Lewy body and Alzheimer type dementia syndromes
.
Lancet
 ,
347
,
696
697
.
Goto
T.
Tanaka
H.
(
2005
).
Handbook of the science of illusion
  (
1st ed.
).
Tokyo
:
University of Tokyo Press
(i
n Japanese
).
Hirayama
K.
(
2013
).
Neuropsychology of visual illusion
.
Shinkei Shinrigaku Zasshi (Japanese Journal of Neuropsychology)
 ,
29
,
113
125
(
in Japanese
).
Huang
Y.
Halliday
G.
(
2013
).
Can we clinically diagnose dementia with Lewy bodies yet?
Translational Neurodegeneration
 ,
2
,
4
.
Hurt
C.
Bhattacharyya
S.
Burns
A.
Camus
V.
Liperoti
R.
Marriott
A.
et al
(
2008
).
Patient and caregiver perspectives of quality of life in dementia. An investigation of the relationship to behavioural and psychological symptoms in dementia
.
Dementia and Geriatric Cognitive Disorders
 ,
26
,
138
146
.
Iseki
E.
(
2010
).
Dementia with Lewy bodies
.
Igaku no ayumi
 ,
235
,
719
724
(i
n Japanese
).
Lezak
M. D.
(
1995
).
Neuropsychological assessment
  (
3rd ed.
).
New York
:
Oxford University Press
.
Translated by Kashima, H., Mimura, M., Muramatsu, T. (2005). Tokyo: Sozo shuppan
.
Maeshima
S.
Osawa
A.
Maeshima
E.
Shimamoto
Y.
Sekiguchi
E.
Kakishita
K.
et al
(
2004
).
Usefulness of a cube-copying test in outpatients with dementia
.
Brain Injury
 ,
18
,
889
898
.
McKeith
I. G.
Dickson
D. W.
Lowe
J.
Emre
M.
O'Brien
J. T.
Feldman
H.
et al
(
2005
).
Consortium on DLB. Diagnosis and management of dementia with Lewy bodies: Third report of the DLB consortium
.
Neurology
 ,
65
,
1863
1872
.
McKhann
G. M.
Knopman
D. S.
Chertkow
H.
Hyman
B. T.
Jack
C. R.
Jr
Kawas
C. H.
et al
(
2011
).
The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
.
Alzheimer‘s & Dementia
 ,
7
,
263
269
.
Metzler-Baddeley
C.
Baddeley
R. J.
Lovell
P. G.
Laffan
A.
Jones
R. W.
(
2010
).
Visual impairments in dementia with Lewy bodies and posterior cortical atrophy
.
Neuropsychology
 ,
24
,
35
48
.
Minoshima
S.
Foster
N. L.
Sima
A. A.
Frey
K. A.
Albin
R. L.
Kuhl
D. E.
(
2001
).
Alzheimer's disease versus dementia with Lewy bodies: Cerebral metabolic distinction with autopsy confirmation
.
Annals of Neurology
 ,
50
,
358
365
.
Mohs
R. C.
(
1994
).
Administration and scoring manual for the Alzheimer‘s disease assessment scale
  (
revised ed.
).
New York
:
Mount Sinai School of Medicine
.
Mori
E.
Shimomura
T.
Fujimori
M.
Hirono
N.
Imamura
T.
Hashimoto
M.
et al
(
2000
).
Visuoperceptual impairment in dementia with Lewy bodies
.
Archives of Neurology
 ,
57
,
489
493
.
Mosimann
U. P.
Mather
G.
Wesnes
K. A.
O'Brien
J. T.
Burn
D. J.
McKeith
I. G.
(
2004
).
Visual perception in Parkinson disease dementia and dementia with Lewy bodies
.
Neurology
 ,
63
,
2091
2096
.
Murayama
N.
Iseki
E.
Yamamoto
R.
Kimura
M.
Eto
K.
Arai
H.
(
2007
).
Utility of the Bender Gestalt Test for differentiation of dementia with Lewy bodies from Alzheimer's disease in patients showing mild to moderate dementia
.
Dementia and Geriatric Cognitive Disorders
 ,
23
,
258
263
.
Murray
M. M.
Herrmann
C. S.
(
2013
).
Illusory contours: A window onto the neurophysiology of constructing perception
.
Trends in Cognitive Sciences
 ,
17
,
471
481
.
Nagahama
Y.
Okina
T.
Suzuki
N.
Matsuda
M.
(
2008
).
Cerebral substrates related to impaired performance in the clock-drawing test in dementia with Lewy bodies
.
Dementia and Geriatric Cognitive Disorders
 ,
25
,
524
530
.
Nelson
P. T.
Schitt
F. A.
Jicha
G. A.
Kryscio
R. J.
Abner
E. L.
Smith
C. D.
et al
(
2010
).
Association between male gender and cortical Lewy body pathology in large autopsy series
.
Journal of Neurology
 ,
257
,
1875
1881
.
Ota
K.
Iseki
E.
Murayama
N.
Chiba
Y.
Fujishiro
H.
Kasanuki
K.
et al
(
2014
).
Three presenile patients in which neuropsychological and neuroimaging examinations suggest possible progression to dementia with Lewy bodies
.
Psychogeriatrics
 ,
14
,
72
80
.
Palmqvist
S.
Hansson
O.
Minthon
L.
Londos
E.
(
2009
).
Practical suggestions on how to differentiate dementia with Lewy bodies from Alzheimer's disease with common cognitive tests
.
International Journal of Geriatric Psychiatry
 ,
24
,
1405
1412
.
Rouleau
N.
Kennedy
C.
McGuire
K.
(
1992
).
Quantitative and qualitative analyses of clock drawings in Alzheimer's and Huntington's disease
.
Brain and Cognition
 ,
18
,
70
87
.
Shimomura
T.
Mori
E.
Yamashita
H.
Imamura
T.
Hirono
N.
Hashimoto
M.
et al
(
1998
).
Cognitive loss in dementia with Lewy bodies and Alzheimer disease
.
Archives of Neurology
 ,
55
,
1547
1552
.
Simard
M.
van Reekum
R.
Chohen
T.
(
2000
).
A review of the cognitive and behavioral symptoms in dementia with Lewy bodies
.
Journal of Neuropsychiatry & Clinical Neurosciences
 ,
12
,
425
450
.
Simard
M.
van Reekum
R.
Myran
D.
(
2003
).
Visuospatial impairment in dementia with Lewy bodies and Alzheimer's disease: A process analysis approach
.
International Journal of Geriatric Psychiatry
 ,
18
,
387
391
.
Tang-Wai
D. F.
Graff-Radford
N. R.
Boeve
B. F.
Dickson
D. W.
Parisi
J. E.
Crook
R.
et al
(
2004
).
Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy
.
Neurology
 ,
63
,
1168
1174
.
Teng
E. L.
Chui
H. C.
(
1987
).
The Modified Mini-Mental State (3MS) examination
.
Journal of Clinical Psychiatry
 ,
48
,
314
318
.
The Committee for the Visual Perception Test, Japanese Society of Aphasiology
. (
1997
).
Visual perception tests for agnosia: VPTA
 .
Tokyo
:
Shinko Igaku Shuppannsha
(
in Japanese
).
Tranel
D.
Vianna
E.
Manzel
K.
Damasio
H.
Grabowski
T.
(
2009
).
Neuroanatomical correlates of the Benton Facial Recognition Test and Judgment of Line Orientation Test
.
Journal of Clinical and Experimental Neuropsychology
 ,
31
,
219
233
.
Walker
Z.
Jaros
E.
Walker
R. W.
Lee
L.
Costa
D. C.
Livingston
G.
et al
(
2007
).
Dementia with Lewy bodies : A comparison of clinical diagnosis, FP-CIT single photon smission computed tomography imaging and autopsy
.
Journal of Neurology, Neurosurgery & Psychiatry
 ,
78
,
1176
1181
.
Yokoi
K.
Nishio
Y.
Uchiyama
M.
Shimomura
T.
Iizuka
O.
Mori
E.
(
2014
).
Hallucinators find meaning in noises: Pareidolic illusions in dementia with Lewy bodies
.
Neuropsychologia
 ,
56
,
245
254
.