RESEARCH ARTICLE

Relationship between regional cerebral blood flow and neuropsychiatric symptoms in dementia with Lewy bodies Taku Yoshida1, Takaaki Mori1, Kiyohiro Yamazaki1, Naomi Sonobe1, Hideaki Shimizu1, Teruhisa Matsumoto1, Keiichi Kikuchi2, Masao Miyagawa2, Teruhito Mochizuki2 and Shu-ichi Ueno1 1

Department of Neuropsychiatry, Graduate School of Medicine, Ehime University, Toon, Ehime Japan Department of Radiology, Graduate School of Medicine, Ehime University, Toon, Ehime Japan Correspondence to: Shu-ichi Ueno, E-mail: [email protected]

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Objective: This aim of this study was to examine the mechanisms underlying the neuropsychiatric symptoms in dementia with Lewy bodies by investigating regional cerebral blood flow. Methods: Participants were 27 patients who fulfilled the diagnostic criteria for probable dementia with Lewy bodies. All subjects underwent single-photon emission computed tomography scans using technetium-99 m hexamethylpropyleneamine oxime. Neuropsychiatric symptoms were evaluated by neuropsychiatric inventory. Multiple regression analyses using neuropsychiatric inventory and voxelbased analyses of covariance of the regional cerebral blood flow images between subjects with or without each neuropsychiatric symptom were performed. Additionally, similar voxel-based analyses of covariance between subjects with each neuropsychiatric symptom and normal subjects were performed. Results: There were no significant correlations in any psychiatric symptoms in multiple regression analyses. All subjects had hallucination but none had euphoria. We analyzed eight neuropsychiatric symptom scores with the exception of hallucination and euphoria using voxel-based analyses of covariance. Significant differences of regional cerebral blood flow were shown in groups with agitation, disinhibition, and irritability. Subjects with agitation showed hypoperfusion in the parietal lobule, the precuneus, and the angular gyrus, and hyperperfusion in the fusiform gyrus, the lingual gyrus, and the thalamus. Subjects with disinhibition showed hypoperfusion in the left frontal gyrus. Subjects with irritability showed hyperperfusion in the right frontal gyrus. There were no significant differences in regional cerebral blood flow between subjects with any neuropsychiatric symptoms and normal subjects. Conclusion: This study reveals that dysfunction of specific brain regions is associated with various neuropsychiatric symptoms in dementia with Lewy bodies. Copyright # 2015 John Wiley & Sons, Ltd. Key words: dementia with Lewy bodies; neuropsychiatric symptoms; SPECT; agitation; disinhibition; irritability History: Received 17 September 2014; Accepted 6 January 2015; Published online 17 February 2015 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/gps.4263

Introduction Dementia with Lewy bodies (DLB) is characterized by symptoms of fluctuating cognition, visual hallucination, and parkinsonism (McKeith et al., 2005) and is the second most common degenerative dementia next to Alzheimer’s disease (McKeith et al., 1996). DLB presents with visual hallucination and various neuropsychiatric symptoms including delusion, agitation, and depression. Neuropsychiatric symptoms such as depression, anxiety, apathy, and irritability Copyright # 2015 John Wiley & Sons, Ltd.

appear from an early stage in DLB, whereas neuropsychiatric symptoms such as hallucination, delusion, agitation, and sleep disorder appear gradually with the progression of the disease (Borroni et al., 2008). Visual hallucination, especially human existence as a hallucination, is known to appear most frequently in DLB (Nagahama et al., 2007). Delusional misidentification is a frequent neuropsychiatric symptom in DLB. Depression is also frequent in DLB, which includes agitation, a decrease in concentration, and loss of Int J Geriatr Psychiatry 2015; 30: 1068–1075

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weight besides depressive mood (Samuels et al., 2004). These various neuropsychiatric symptoms frequently disturb their daily life and have a significantly negative effect on patient’s quality of life and caregivers’ burden (Borroni et al., 2008). There have been many reports of brain imaging in DLB. For example, using structural brain imaging in DLB, the volume reduction of the hippocampus in DLB was reported to be less than that in Alzheimer’s disease (AD) (Hashimoto et al., 1998), whereas no significant volume reduction of the occipital lobe in either DLB or AD was observed compared with that in controls (Middelkoop et al., 2001). In functional brain imaging of DLB, visual hallucination is associated with both occipital hypoperfusion (Imamura et al., 1999) and hypometabolism (Ishii et al., 1998). Acetylcholinesterase inhibitors can improve visual hallucination in DLB (McKeith et al., 2000), and these drugs increase regional cerebral blood flow (rCBF) in the occipital lobe (Mori et al., 2006). A single-photon emission computed tomography (SPECT) study found that delusion was associated with hyperperfusion in the frontal lobe, while misidentification was associated with hypoperfusion in the hippocampus, insula, ventral striatum, and inferior frontal gyrus (Nagahama et al., 2010). A recent positron emission tomography study also indicated that hypometabolism in the visual association areas, rather than the primary visual cortex, was associated with visual hallucination in DLB (Perneczk et al., 2008). Overall, these studies suggest that occipital dysfunction is associated with visual hallucination. However, there are few reports examining the relationship between rCBF and neuropsychiatric symptoms excluding visual hallucination. Thus, the aim of the present study was to investigate the relationship between rCBF and various neuropsychiatric symptoms besides visual hallucination.

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left-handed, taking acetylcholinesterase inhibitors, or had past histories of psychiatric diseases and obvious cerebrovascular lesions in MRI or CT. All patients were confirmed to present visual hallucination. Twenty-seven DLB patients who fulfilled these criteria participated in our study. All subjects were examined with mini-mental state examinations (MMSE), neuropsychiatric inventory (NPI), and SPECT. NPI is an evaluation scale of neuropsychiatric symptoms of participants that is performed with reliable caregivers. It consists of 10 subscales including delusion, hallucination, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, and aberrant motor behavior. The scores of NPI subscales are the products of severity (0–4) and frequency (0–3) for neuropsychiatric symptoms. Demographic data (age, sex, disease duration, years of education, score of MMSE, and score of NPI) of the patients are shown in Table 1. Numbers of patients with fluctuating cognition, visual hallucination, parkinsonism, and treatment with major tranquilizer are also presented. We also recruited 20 normal control subjects. The demographic data of the normal subjects were 73.0 ± 5.4 years of age (mean ± standard deviation; range 62–85), MMSE 29.0 ± 1, and 14 women and 6 men. This study was approved by the Institutional Review Board of Ehime University Graduate School of Medicine. Single-photon emission computed tomography imaging. All SPECT scans were performed using 740 MBq

technetium-99 m hexamethylpropyleneamine oxime (99mTc-HMPAO) with eyes closed in a quiet dimly lit room. The SPECT system used a four-head rotating gamma camera (SPECT RW-3000; HITACHI, Tokyo, Japan) equipped with high-resolution low-energy collimators with a spatial resolution of 7.5 mm full width Table 1 Demographic summary of subjects (n = 27)

Subjects and methods Subjects

We recruited DLB patients who were consulted at the Department of Neuropsychiatry of Ehime University Hospital. Patients fulfilled the diagnostic criteria for probable DLB and were living with at least one caregiver. All patients received a medical history interview and neurological examinations by trained psychiatrists. The subjects also received magnetic resonance imaging (MRI) or computed tomographic imaging (CT) of the brain. We excluded subjects that were Copyright # 2015 John Wiley & Sons, Ltd.

Mean ± SD Age (years) Sex (female : male) Disease duration (years) Education (years) MMSE total score NPI-10 total score Fluctuating cognition Visual hallucination Parkinsonism Treatment with major tranquilizer

n

77.5 ± 5.5

Range 64–92

13:14 1.7 ± 1.1 9.0 ± 3.1 18.8 ± 5.5 19.6 ± 28.2

0–4 0–14 9–29 2–80 19 (70.4%) 27 (100%) 16 (59.3%) 4 (14.8%)

SD, standard deviation; MMSE, mini-mental state examinations; NPI, neuropsychiatric inventory.

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at half maximum. Data were obtained from the 140 KeV photo peak (10% window) over a 360° rotation and 128 × 128 matrix. The slice thickness and axial resolution of SPECT images were 2.0 mm. The stepand-shoot format was used (acquisition time: 20 s/step; zoom factor: 1.33×). Transaxial images of 99m Tc-HMPAO SPECT were reconstructed by filtered back projection using Butterworth and ramp filters (cut-off frequency 0.12 cycle/cm) with attenuation correction (Chang, 0.08/cm). Statistical image analysis

Single-photon emission computed tomography data were analyzed with statistical parametric mapping (SPM8; Wellcome Department of Cognitive Neurology, London, UK) on MATLAB R2012a (The MathWorks. Inc., Natick, MA, USA). The rCBF ratio was calculated on the basis of the average counts of the region of interest value in the cerebellum. All images were spatially transformed to the SPM8 SPECT template. The spatially normalized images were resliced to a 2 × 2 × 2-mm voxel size. After normalization, the images were smoothed with an isotropic 16-mm full width at half maximum Gaussian filter. First, we compared rCBF of 27 DLB subjects and 20 normal subjects using a two-sample t-test model. We performed t-test using SPM8 (uncorrected p < 0.001), and age was used as a covariate. The rCBFs of the parietal and occipital lobes were lower in DLB subjects compared with normal subjects (Figure S1). Second, we used multiple regression models in SPM8 to perform multivariate analysis of the relationship between rCBF and various neuropsychiatric symptoms, excluding previously analyzed parietal and occipital areas. The scores of NPI subscales were used for correlation analysis. We used age, sex, disease duration, years of education, total score of MMSE, fluctuating cognition, parkinsonism, and use of a major tranquilizer as covariates. We set the uncorrected threshold at p < 0.001 and the extent threshold at 10 voxels. Third, we performed voxel-based analysis of covariance (ANCOVA) of the rCBF images between DLB subjects with and without each neuropsychiatric symptom, excluding first analyzed parietal and occipital areas. DLB subjects with neuropsychiatric symptoms were defined with a cut-off score of 1 for each NPI subscale. We used the same covariates as for multivariate analyses. We set the uncorrected threshold at p < 0.001 and the extent threshold at 10 voxels. Finally, we performed ANCOVA of the rCBF images between DLB subjects with each neuropsychiatric symptom and normal subjects, excluding the previously analyzed parietal Copyright # 2015 John Wiley & Sons, Ltd.

T. Yoshida et al.

and occipital areas. We used age as a covariate, and we set the uncorrected threshold at p < 0.001 and the extent threshold at 10 voxels. Results The rCBFs of the parietal and occipital lobes in DLB subjects were lower compared with normal subjects. There were no areas of hyperperfusion in DLB subjects compared with normal subjects. Previous studies suggest that dysfunction of the occipital lobe can cause visual hallucination, which may be related to other symptoms. We considered that the various psychiatric symptoms were caused by relative hypoperfusion or hyperperfusion in other regions of brain, in addition to hypoperfusion in the occipital lobe. Therefore, we performed additional analyses, excluding the previously analyzed parietal and occipital areas. Neuropsychiatric inventory subscales in the DLB subjects are shown in Table 2. All patients had hallucination but none had euphoria. By multiple regression models in SPM8, we found no significant correlations in any psychiatric symptom. Next, we performed ANCOVA between DLB subjects with and without eight neuropsychiatric symptoms excluding hallucination and euphoria. There were significant differences of rCBF in groups of agitation, disinhibition, and irritability. Subjects with agitation showed hypoperfusion in the left inferior parietal lobule (Figure 1(a); FWE: p = 0.029, 130 voxels, Z score = 4.60), the left precuneus (43 voxels, Z score = 3.54), and the left angular gyrus (22 voxels, Z score = 3.37). Furthermore, agitated subjects showed hyperperfusion in the right fusiform gyrus (Figure 1(b); FWE: p = 0.043, Table 2 Neuropsychiatric inventory subscales in the subjects (n = 27) Score in patients with each symptom Neuropsychiatric symptoms Delusion Hallucination Agitation Depression Anxiety Euphoria Apathy Disinhibition Irritability Aberrant motor behavior

n

Mean ± SD

Range

23 (79.3%) 27 (100%) 12 (44.4%) 12 (44.4%) 12 (44.4%) 0 14 (51.9%) 6 (22.2%) 11 (40.7%) 8 (29.6%)

7.6 ± 3.9 7.3 ± 3.7 6.3 ± 4.2 3.3 ± 2.3 4.6 ± 3.9 — 5.3 ± 2.8 5.3 ± 2.7 5.5 ± 3.3 6.9 ± 3.3

0–12 0–12 0–12 0–6 0–12 — 0–12 0–9 0–12 0–12

SD, standard deviation.

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hypoperfusion in the left middle frontal gyrus and the left inferior frontal gyrus (Figure 1(c); FWE: p = 0.044, 673 voxels, Z score =4.51), and the postcentral gyrus (108 voxels, Z score = 3.59). Subjects with irritability showed hyperperfusion in the right middle frontal gyrus (Figure 1(d); FWE: p = 0.023, 120 voxels, Z score = 4.67). Figure 1 and Table 3 show these results of the SPM analyses. There were no differences in rCBF between the groups for delusion, depression, anxiety, apathy, and aberrant motor behavior. We performed ANCOVA between DLB subjects with neuropsychiatric symptoms and normal subjects. We focused on the symptoms that exhibited significant differences in rCBF in the prior analyses. The results of the SPM analyses are shown in Figure 2. DLB subjects with agitation showed hypoperfusion in the left precuneus (Figure 2(a); 75 voxels, Z score = 4.00), the right precuneus (259 voxels, Z score = 3.95), the right inferior parietal lobule (243 voxels, Z score = 3.82), and the left inferior parietal lobule (342 voxels, Z score = 3.73). Furthermore, agitated subjects in DLB showed hyperperfusion in the right parahippocampal gyrus (Figure 2(b); 60 voxels, Z score = 3.75) and the right insula (12 voxels, Z score = 3.27). DLB subjects with disinhibition showed hypoperfusion in the left inferior parietal lobule (Figure 2(c); 440 voxels, Z score = 3.94), the left precuneus (27 voxels, Z score = 3.71), and the left postcentral gyrus (61 voxels, Z score = 3.60). DLB subjects with irritability showed hyperperfusion in the left superior temporal gyrus (Figure 2(d); 88 voxels, Z score = 4.12) and the right medial frontal gyrus (10 voxels, Z score = 3.21). However, there were no significant differences in rCBF between normal subjects and DLB subjects with neuropsychiatric symptoms in groups of agitation, disinhibition, and irritability.

Figure 1 Significant perfusion changes in regional cerebral blood flow between dementia with Lewy bodies (DLB) subjects with and without each neuropsychiatric symptom in groups of agitation, disinhibition, and irritability (analysis of covariance, uncorrected p < 0.001). (a) Hypoperfusion in agitation-present DLB compared with nonagitation DLB. (b) Hyperperfusion in agitation-present DLB compared with nonagitation DLB. (c) Hypoperfusion in disinhibition-present DLB compared with nondisinhibition DLB. (d) Hyperperfusion in irritability-present DLB compared with nonirritability DLB.

281 voxels, Z score =4.49), the left lingual gyrus (34 voxels, Z score = 3.80), right thalamus (28 voxels, Z score = 3.77), and the left thalamus (41 voxels, Z score = 3.75). Subjects with disinhibition showed Copyright # 2015 John Wiley & Sons, Ltd.

Discussion This is the first study to show the relationship between rCBF and neuropsychiatric symptoms with the exception of visual hallucination in DLB. We found no significant correlations in multiple regression analysis. Nevertheless, between DLB subjects with and without neuropsychiatric symptoms, subjects with agitation showed hypoperfusion in the left inferior parietal lobule and hyperperfusion in the right fusiform gyrus, subjects with disinhibition showed hypoperfusion in the left middle and inferior frontal gyrus, and subjects with irritability showed hyperperfusion in the right middle frontal gyrus. However, there were no Int J Geriatr Psychiatry 2015; 30: 1068–1075

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T. Yoshida et al. Table 3 Significant perfusion changes in regional cerebral blood flow between dementia with Lewy bodies subjects with and without each neuropsychiatric symptom Regions

Voxels

(a) Hypoperfusion in subjects with agitation Left inferior parietal lobule 130 Left precuneus 43 Left angular gyrus 22 (b) Hyperperfusion in subjects with agitation Right fusiform gyrus 281 Left lingual gyrus 34 Right thalamus 28 Left thalamus 41 (c) Hypoperfusion in subjects with disinhibition Left middle frontal gyrus 673 Left postcentral gyrus 108 (d) Hyperperfusion in subjects with irritability Right middle frontal gyrus 120

FWE p

x

y

z

Z score

0.029 0.600 0.762

44 20 44

36 54 62

28 44 24

4.60 3.54 3.37

0.043 0.355 0.380 0.399

30 12 4 2

40 46 16 16

24 6 2 2

4.49 3.80 3.77 3.75

0.044 0.567

38 66

10 14

36 30

4.51 3.59

0.023

32

30

26

4.67

FWE p, peak p-value (analysis of covariance, FWE corrected); x, y, z, peak coordinates in Montreal Neurological Institute space; Z score, peak z score in statistical parametric mapping 8 (analysis of covariance, uncorrected p < 0.001).

significant differences in rCBF in any neuropsychiatric symptoms. A summary of these results for each neuropsychiatric symptom is shown in Figure 3. There was an overlap in part of the hypoperfusion observed in the left parietal lobule and the left precuneus in subjects with agitation. However, there was no overlap between any brain regions for hyperperfusion in subjects with agitation, hypoperfusion in subjects with disinhibition, or hyperperfusion in subjects with irritability. With respect to significant differences in rCBF, we found that agitation was associated with hypoperfusion in the parietal lobule and hyperperfusion in the fusiform gyrus, whereas disinhibition was associated with hypoperfusion in the middle and inferior frontal gyrus, and irritability was associated with hyperperfusion in the frontal gyrus. With respect to agitation and rCBF changes, the parietal lobe is important in spatial cording of visual and somatic sensory information in body centered coordinates (Galati et al., 2001). Inferior parietal cortex activity was reported to be lower in violent schizophrenia compared with nonviolent schizophrenia by functional MRI (Kumari et al., 2006). The parietal cortex participates in the unification of sensory input and the formation of abstract concepts, while its dysfunction leads to agitation because of lack of social information processing (Raine et al., 1997). Hypoperfusion in DLB subjects with agitation occurred in similar brain regions to that in DLB subjects without agitation and normal subjects. The fusiform gyrus plays a role in face perception (Kanwisher et al., 1997), and region of the fusiform face area leads to prosopagnosia (Shah et al., 2001; Barton et al., 2002). Copyright # 2015 John Wiley & Sons, Ltd.

Activity of the fusiform gyrus and limbic system has also been reported to be related to violence (Lee et al., 2009). Hyperperfusion in DLB subjects with agitation compared with normal subjects was observed in the parahippocampal gyrus. The parahippocampal region is associated with visual scene responses and face processing (Epstein et al., 1999; Bar et al., 2008). Visual cognitive impairment is observed in DLB, so it is possible that the agitation is caused by dysfunction of the fusiform gyrus and the parahippocampal gyrus. We found a significant association between hypoperfusion in the middle and inferior frontal gyrus and disinhibition. Although the frontal lobe has various functions, the prefrontal cortex participates in working memory, executive function, attention, affective reaction, motivation, and control of impulsive behavior (Fuster, 2001). By MRI, a reduction in brain volume in the inferior frontal gyrus, orbitofrontal cortex, anterior cingulate cortex, and temporal lobe were correlated with disinhibition in dementia (Krueger et al., 2011). In addition, brain volume of the middle frontal gyrus was reported to be associated with executive function. Executive function is involved in the control of impulsivity and the prediction of behavior result, whereas dysfunction of the frontal gyrus may cause disinhibitory behaviors. Hypoperfusion in DLB subjects with disinhibition compared with normal subjects was observed in the inferior parietal lobule. As previously described, the inferior parietal lobule hypoperfusion was related to agitation (Raine et al., 1997; Kumari et al., 2006). In addition, dysfunction of the inferior parietal lobule and the Int J Geriatr Psychiatry 2015; 30: 1068–1075

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Figure 2 Perfusion changes in regional cerebral blood flow between normal subjects and dementia with Lewy bodies (DLB) subjects for each neuropsychiatric symptom in groups of agitation, disinhibition, and irritability (analysis of covariance, uncorrected p < 0.001). (a) Hypoperfusion in agitation-present DLB compared with normal subjects. (b) Hyperperfusion in agitation-present DLB compared with normal subjects. (c) Hypoperfusion in disinhibition-present DLB compared with normal subjects. (d) Hyperperfusion in irritability-present DLB compared with normal subjects.

frontal lobe was reported to be related to disinhibition (Asahi et al., 2004; Claus et al., 2013). We also found that hyperperfusion in the frontal gyrus was significantly associated with irritability. In a positron emission tomography study, irritability Copyright # 2015 John Wiley & Sons, Ltd.

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and the instability of affections were associated with frontal lobe and limbic dysfunction (Salavert et al., 2011). Therefore, hyperperfusion of this region may also cause irritability in DLB. Hyperperfusion in DLB subjects with irritability compared with normal subjects was observed in the superior temporal gyrus. The temporal cortex is known to participate in auditory perception, language perception, and visual perception (Hall et al., 2003; Hickok, 2012). Although a relationship between the temporal lobule and irritability has not been previously reported, several studies have suggested that the network comprising the prefrontal lobe, temporal lobe, and cingulate regions is associated with emotional regulation. Therefore, dysfunction of the temporal lobe leads to the failure of this network, which may cause irritability. The pathology of DLB is characterized by diffuse accumulation of Lewy bodies and Lewy neurites throughout the brain. The presence of cortical Lewy bodies was higher in the anterior frontal, cingulate, temporal, and insular cortices than in other brain regions (Kosaka, 1990). Lewy pathology was also higher in the secondary visual pathway than in the primary visual pathway (Yamamoto et al., 2006). Lewy pathology spreads from the amygdala to both the limbic cortex and the neocortex with DLB progression (Marui et al., 2002). Many patients with probable clinical DLB have a pathologically neocortical type with intermediate- or high likelihood DLB pathology (Fujimi et al., 2008; Fujishiro et al., 2008). Lewy pathology may include neurodegeneration and destruction of the acetylcholinergic pathway, and its extensive destruction causes various symptomatologies in DLB (Baskys, 2004). In addition to occipital hypoperfusion, dysfunction in various parts of the cerebral cortex may cause various neuropsychiatric symptoms. Therefore, it is possible that the difference of spreading Lewy bodies in each individual case leads to an imbalance of rCBF and causes various neuropsychiatric symptoms in DLB. The lack of significant differences in rCBF in the multiple regression analysis in the present study may be because of the following factors. As cognitive fluctuation in DLB subjects was related to fluctuations of neuropsychiatric symptoms, the NPI scores may have varied markedly. In addition, as NPI is an evaluation scale determined by a structured caregiver interview, there is potential for evaluator bias. Further, the results of the two analyses in DLB subjects with psychiatric symptoms compared with DLB subjects without psychiatric symptoms and normal subjects were partially different. This may have been Int J Geriatr Psychiatry 2015; 30: 1068–1075

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Figure 3 Summary of regional cerebral blood flow between comparison of dementia with Lewy bodies (DLB) subjects with and without neuropsychiatric symptoms and comparison of DLB subjects with neuropsychiatric symptoms and normal subjects. For comparison of DLB subjects with and without neuropsychiatric symptoms, regions of hypoperfusion are shown in blue, and regions of hyperperfusion are shown in red. For comparison of DLB subjects with neuropsychiatric symptoms and normal subjects, regions of hypoperfusion are shown in green, and regions of hyperperfusion are shown in purple.

because rCBF in DLB subjects with psychiatric symptoms compared with DLB subjects without psychiatric symptoms changed more than DLB subjects with psychiatric symptoms compared with normal subjects. There are also several limitations to our study. The sample size in our study was small, as many DLB patients were already prescribed acetylcholinesterase inhibitors, which may have modified blood perfusion of the brain. Therefore, it was difficult to perform family-wise correction. Future studies are planned with increased numbers of cases. In addition, the progression of parkinsonism was not assessed by any evaluation scales. Finally, fluctuating cognition and Copyright # 2015 John Wiley & Sons, Ltd.

impaired attention, which may affect neuropsychiatric symptoms, could not be evaluated. Further studies assessing parkinsonism and cognitive fluctuations may indicate the affected regions more in detail. This is an exploratory study to investigate the relationship between rCBF and various neuropsychiatric symptoms. Therefore, future studies should examine biological makers for other neuropsychiatric symptoms in DLB. Furthering our understanding of the neural basis of neuropsychiatric symptoms in DLB is important for development of future medical treatments. We plan to perform similar studies for other neurocognitive disorders, which may help to clarify the neural basis for various neuropsychiatric symptoms. Int J Geriatr Psychiatry 2015; 30: 1068–1075

Neuropsychiatric symptoms and rCBF in DLB

Conclusion Using functional brain imaging, we found that neuropsychiatric symptoms in DLB are related to dysfunction in the frontal and the parietal lobes. Conflict of interest None declared.

Key points

• • •

There are few reports examining the relationship between regional cerebral blood flow and neuropsychiatric symptoms excluding visual hallucination in dementia with Lewy bodies. This study revealed that agitation was associated with hypoperfusion in the parietal lobule and hyperperfusion in the fusiform gyrus; disinhibition was associated with hypoperfusion in the frontal gyrus; and irritability was associated with hyperperfusion in frontal gyrus. Dysfunctions of several parts of the brain may cause various neuropsychiatric symptoms in dementia with Lewy bodies.

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Supporting information Additional supporting information may be found in the online version of this article at the publisher’s web site.

Int J Geriatr Psychiatry 2015; 30: 1068–1075

Relationship between regional cerebral blood flow and neuropsychiatric symptoms in dementia with Lewy bodies.

This aim of this study was to examine the mechanisms underlying the neuropsychiatric symptoms in dementia with Lewy bodies by investigating regional c...
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